ACTIVE_NOT_RECRUITING

Venetoclax Basket Trial for High Risk Hematologic Malignancies

Conditions

Myelodysplastic Syndromes, de Novo Myelodysplastic Syndromes, Secondary Myelodysplastic Syndromes, Previously Treated Treatment-Related Acute Myeloid Leukemia Therapy-Related Myelodysplastic Syndrome Acute Lymphoblastic Leukemia, in Relapse Acute Lymphoblastic Leukemia With Failed Remission Lymphoblastic Lymphoma, in Relapse Lymphoblastic Lymphoma, Refractory Acute Leukemia of Ambiguous Lineage in Relapse Acute Leukemia of Ambiguous Lineage Myelodysplastic Syndrome (MDS)Treatment-related Acute Myelogenous Leukemia AML arising from MDS Relapsed or Refractory Acute Lymphoblastic Leukemia Relapsed or Refractory Acute Lymphoblastic Lymphoma Relapsed or Refractory MDS Treatment-related MDS Relapsed or Refractory Acute leukemia of ambiguous lineage

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This trial is evaluating the safety and tolerability of venetoclax with chemotherapy in pediatric and young adult patients with hematologic malignancies, including myelodysplastic syndrome (MDS), acute myeloid leukemia derived from myelodysplastic syndrome (MDS/AML), and acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). The names of the study drugs involved in this study are below. Please note this is a list for the study as a whole, participants will receive drugs according to disease cohort. * Venetoclax * Azacitidine * Cytarabine * Methotrexate * Hydrocortisone * Leucovorin * Dexamethasone * Vincristine * Doxorubicin * Dexrazoxane * Calaspargase pegol * Hydrocortisone

Official Title

A Phase I Study of Venetoclax in Combination With Cytotoxic Chemotherapy, Including Calaspargase Pegol, for Children, Adolescents and Young Adults With High-Risk Hematologic Malignancies

Quick Facts

Study Start:2023-03-29

Study Completion:2028-07-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05292664

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year to 40 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* MDS, AML arising from MDS (MDS/AML), therapy related myeloid neoplasm (tMDS/AML) meeting at least one of the following criteria: * MDS with excess blasts (\>10%) * MDS with blasts \<10% with high-risk features * MDS refractory to initial treatment * Relapsed MDS * MDS/AML: May be newly diagnosed or relapsed/refractory disease. * Therapy related myeloid neoplasm (tMDS/AML): May be initial or relapsed/refractory disease. * Note: MDS or MDS/AML may be derived from a germline predisposition to myeloid malignancy as long as that condition does not confer increased toxicity to treatment. * Age ≤ 40 years of age, except the following subjects that must be \<18 years to enroll * Subjects with MDS/AML that have not received prior therapy * Subjects enrolled onto Dose level -2. * Lansky/Karnofsky performance status ≥ 50% * Participants must have fully recovered from the acute toxic effects of all and meet all of the following criteria: * Myelosuppressive chemotherapy: 14 days, or 5 half-lifes (whichever is shorter) must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without a "wash-out" period * Standard maintenance therapy: dexamethasone/prednisone, vincristine, 6MP, low dose methotrexate) * Hydroxyurea * Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine. * Radiation therapy (XRT): * Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry * XRT for chloroma does not require a washout period. * Palliative XRT does not require a washout * Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days, or 5 half-lifes, whichever is shorter) must have elapsed since the completion of therapy. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. * Immunotherapy: At least 30 days after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy and checkpoint inhibitors. * Monoclonal antibodies: At least 3 half-lives of the antibody * Prior hematopoietic stem cell transplant (HSCT): * Allogeneic HSCT \> 90 days of study entry * No evidence of graft-versus-host-disease (GVHD) * Adequate organ function, as defined by * Serum alanine aminotransferase (ALT) ≤5X upper limit of normal (ULN) * Direct bilirubin ≤ 3X * Ejection fraction ≥ 50% or shortening fraction of ≥ 24% on screening echocardiogram. * Female participants of childbearing potential must have a negative urine or serum HCG prior to study entry and at the start of therapy. All females of childbearing potential must refrain from breastfeeding during study participation, and all male and females of childbearing potential must agree to use an effective form of contraception (abstinence, hormonal, or barrier) prior to study entry, for duration of participation, and for a minimum of 30 days following the last dose of treatment. * MDS, MDS/AML, therapy related myeloid neoplasm (tMDS/AML) that is derived from the following germline disorders: * Dyskeratosis Congenita or associated telomeropathies * Fanconi Anemia * Nijmegen Breakage * Other related disorders with high risk of toxicity may be eligible for this cohort after discussion with the Sponsor-Investigator. * And meets at least one the following disease characteristics: * MDS with excess blasts (\>10%) * MDS with blasts \<10% with high-risk features * MDS refractory to initial treatment * Relapsed MDS * MDS/AML: May be newly diagnosed or relapsed/refractory disease. * Therapy related myeloid neoplasm (tMDS/AML): May be initial or relapsed/refractory disease. * Age ≤ 40 years of age * Lansky/Karnofsky performance status ≥ 50% * Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and meet all of the following criteria: * Myelosuppressive chemotherapy: 14 days, or 5 half-lifes (which ever is shorter) must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without a "wash-out" period * Standard maintenance therapy: dexamethasone/prednisone, vincristine, 6MP, low dose methotrexate * Hydroxyurea * Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine. * Radiation therapy (XRT): * Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry * XRT for chloroma does not require a washout period. * Palliative XRT does not require a washout * Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days, or 5 half-lifes, whichever is shorter) must have elapsed since the completion of therapy. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. * Immunotherapy: At least 30 days after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy and checkpoint inhibitors. * Monoclonal antibodies: At least 3 half-lives of the antibody * Prior hematopoietic stem cell transplant (HSCT): Must meet all of the following conditions: * Allogeneic HSCT \> 90 days of study entry * No evidence of graft-versus-host-disease (GVHD) * Adequate organ function, as defined by * Serum alanine aminotransferase (ALT) ≤5X upper limit of normal (ULN) * Direct bilirubin ≤ 3X upper limit of normal for age and institution. * Ejection fraction ≥ 50% or shortening fraction of ≥ 24% on screening echocardiogram. * Because of the teratogenic effects of venetoclax on developing fetuses, female participants of childbearing potential must have a negative urine or serum HCG prior to study entry and at the start of therapy. All females of childbearing potential must refrain from breastfeeding during study participation, and all male and females of childbearing potential must agree to use an effective form of contraception (abstinence, hormonal, or barrier) prior to study entry, for duration of participation, and for a minimum of 30 days following the last dose of treatment. * Part I: B-cell or T-cell acute lymphoblastic leukemia (ALL), mixed phenotype acute lymphoblastic leukemia (MPAL) or lymphoblastic lymphoma (LBL) in first or greater relapse or refractory to at least 1 prior remission induction attempt. * For ALL/MPAL: Bone marrow involvement ≥ 5% by aspirate morphology or ≥ 1% assessable by flow cytometry or validated molecular minimal residual disease (MRD) testing * For LBL: Radiographically detectable mass or lymph node involvement * Part II: Histologically confirmed diagnosis of one of the following: * T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL) in first or greater relapse or refractory to at least 1 prior remission induction attempt. * For T-ALL: Bone marrow involvement ≥ 5% by aspirate morphology or ≥ 1% assessable by morphology, flow cytometry or validated MRD testing * For T-LBL (biopsy proven at current or prior relapse): Radiographically detectable mass or lymph node involvement OR * Relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) with bone marrow involvement ≥1% (assessable by morphology, flow cytometry or validated MRD testing) and at least one of the following characteristics: * First relapse with adverse biologic determinants as described below: * KMT2A rearrangement * Low hypodiploidy, defined as ≤ 40 chromosomes * t(17;19) * IKZF1 deletion (without targetable ABL1 fusion) * Ph-like ALL (without targetable ABL1 fusion) * Other biologic determinants with adverse prognosis in discussion with the Sponsor-Investigator * Early first bone marrow relapse occurring \<36 months from initial diagnosis * Primary refractory ALL that has failed 1 prior induction attempt * Age: ≥ 1 and ≤ 21 years of age * Lansky/Karnofsky performance status ≥ 50% * Participants must have fully recovered from the acute toxic effects of all prior and meet all of the following criteria: * Myelosuppressive chemotherapy: 14 days, or 5 half-lives, whichever is shorter, must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without a "wash-out" period: * Standard maintenance therapy: dexamethasone/prednisone, vincristine, 6MP, low dose methotrexate * Hydroxyurea * Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine. * Radiation therapy (XRT): * Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry * XRT for chloroma does not require a washout period. * Palliative XRT does not require a washout * Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days, or 5 half-lifes, whichever is shorter) must have elapsed since the completion of therapy. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. * Immunotherapy: At least 30 days after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy and checkpoint inhibitors. * Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody * Prior hematopoietic stem cell transplant (HSCT): Patients who have received HSCT are eligible, but must meet all of the following conditions: * Allogeneic HSCT \> 90 days of study entry * No evidence of graft-versus-host-disease (GVHD) * Adequate organ function, as defined by the following laboratory values: * Serum alanine aminotransferase (ALT) ≤5X upper limit of normal (ULN), unless deemed secondary to leukemic involvement in discussion with site PI.) * Direct bilirubin ≤ 3X upper limit of normal for age and institution. * Serum amylase ≤ 3X institutional ULN . * Cardiac function as defined as below: * Ejection fraction ≥ 50% or shortening fraction of ≥ 24% on screening echocardiogram. * Maximum prior cumulative doxorubicin dose ≤ 360 mg/m2 or equivalent * Because of the teratogenic effects of venetoclax on developing fetuses, female participants of childbearing potential must have a negative urine or serum HCG prior to study entry and at the start of therapy. All females of childbearing potential must refrain from breastfeeding during study participation, and all male and females of childbearing potential must agree to use an effective non-hormonal form of contraception (abstinence, barrier) prior to study entry, for duration of participation, and for a minimum of 3 months following the last dose of treatment (as calaspargase pegol can render hormonal contraceptives ineffective). * Use of strong or moderate CYP3A inhibitors/inducers within 3 days of study entry * Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD * Individuals with known active hepatitis; baseline testing not required. * Patients with systemic infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. * Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required. * Pregnant or nursing women are excluded. * Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results. * Use of strong or moderate CYP3A inhibitors/inducers within 3 days of study entry * Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD * Individuals with known active hepatitis; baseline testing not required. * Patients with systemic infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. * Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required. * Pregnant or nursing women are excluded. * Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results. * Use of strong or moderate CYP3A inhibitors/inducers within 3 days of study entry * Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD, or who are less than 90 days from stem cell infusion * Individuals with known active hepatitis; baseline testing not required. * Patients with systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. * Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required. * Pregnant or nursing women are excluded * Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results. * Individuals with a history of allergic reactions to any of the agents being used in this trial, with the exception of pegaspargase or calaspargase pegol. Participants with a history of allergy to pegylated formulation of asparasginase are allowed on study but should receive commercial supply of asparaginase Erwinia chrysanthemi (Erwinaze), crisantaspase (Erwinase), or asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze) instead of calaspargase pegol (see Sections 6.2.6 and 6.2.7). Individuals with a history of allergy to Erwinaze, Erwinase or Rylaze are excluded from the study. * History of asparaginase-associated pancreatitis. * Known, active and propagating deep venous thrombus (DVT). * Individuals with isolated CNS or testicular relapse. * Presence of surface immunoglobulin by flow cytometry and/or known t(8;14), t(2;8), or t(8;22). * Individuals with a history of a different malignancy are ineligible except for the following circumstances: * Individuals are eligible if they have been disease-free for at least 1 year and are deemed by the investigator to be at low risk for recurrence of that malignancy. * Individuals with the following cancers are eligible if diagnosed and treated within the past year: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

* MDS, AML arising from MDS (MDS/AML), therapy related myeloid neoplasm (tMDS/AML) meeting at least one of the following criteria:
* MDS with excess blasts (\>10%)
* MDS with blasts \<10% with high-risk features
* MDS refractory to initial treatment
* Relapsed MDS
* MDS/AML: May be newly diagnosed or relapsed/refractory disease.
* Therapy related myeloid neoplasm (tMDS/AML): May be initial or relapsed/refractory disease.
* Note: MDS or MDS/AML may be derived from a germline predisposition to myeloid malignancy as long as that condition does not confer increased toxicity to treatment.
* Age ≤ 40 years of age, except the following subjects that must be \<18 years to enroll
* Subjects with MDS/AML that have not received prior therapy
* Subjects enrolled onto Dose level -2.
* Lansky/Karnofsky performance status ≥ 50%
* Participants must have fully recovered from the acute toxic effects of all and meet all of the following criteria:
* Myelosuppressive chemotherapy: 14 days, or 5 half-lifes (whichever is shorter) must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without a "wash-out" period
* Standard maintenance therapy: dexamethasone/prednisone, vincristine, 6MP, low dose methotrexate)
* Hydroxyurea
* Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine.
* Radiation therapy (XRT):
* Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry
* XRT for chloroma does not require a washout period.
* Palliative XRT does not require a washout
* Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days, or 5 half-lifes, whichever is shorter) must have elapsed since the completion of therapy. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
* Immunotherapy: At least 30 days after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy and checkpoint inhibitors.
* Monoclonal antibodies: At least 3 half-lives of the antibody
* Prior hematopoietic stem cell transplant (HSCT):
* Allogeneic HSCT \> 90 days of study entry
* No evidence of graft-versus-host-disease (GVHD)
* Adequate organ function, as defined by
* Serum alanine aminotransferase (ALT) ≤5X upper limit of normal (ULN)
* Direct bilirubin ≤ 3X
* Ejection fraction ≥ 50% or shortening fraction of ≥ 24% on screening echocardiogram.
* Female participants of childbearing potential must have a negative urine or serum HCG prior to study entry and at the start of therapy. All females of childbearing potential must refrain from breastfeeding during study participation, and all male and females of childbearing potential must agree to use an effective form of contraception (abstinence, hormonal, or barrier) prior to study entry, for duration of participation, and for a minimum of 30 days following the last dose of treatment.
* MDS, MDS/AML, therapy related myeloid neoplasm (tMDS/AML) that is derived from the following germline disorders:
* Dyskeratosis Congenita or associated telomeropathies
* Fanconi Anemia
* Nijmegen Breakage
* Other related disorders with high risk of toxicity may be eligible for this cohort after discussion with the Sponsor-Investigator.
* And meets at least one the following disease characteristics:
* MDS with excess blasts (\>10%)
* MDS with blasts \<10% with high-risk features
* MDS refractory to initial treatment
* Relapsed MDS
* MDS/AML: May be newly diagnosed or relapsed/refractory disease.
* Therapy related myeloid neoplasm (tMDS/AML): May be initial or relapsed/refractory disease.
* Age ≤ 40 years of age
* Lansky/Karnofsky performance status ≥ 50%
* Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and meet all of the following criteria:
* Myelosuppressive chemotherapy: 14 days, or 5 half-lifes (which ever is shorter) must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without a "wash-out" period
* Standard maintenance therapy: dexamethasone/prednisone, vincristine, 6MP, low dose methotrexate
* Hydroxyurea
* Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine.
* Radiation therapy (XRT):
* Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry
* XRT for chloroma does not require a washout period.
* Palliative XRT does not require a washout
* Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days, or 5 half-lifes, whichever is shorter) must have elapsed since the completion of therapy. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
* Immunotherapy: At least 30 days after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy and checkpoint inhibitors.
* Monoclonal antibodies: At least 3 half-lives of the antibody
* Prior hematopoietic stem cell transplant (HSCT): Must meet all of the following conditions:
* Allogeneic HSCT \> 90 days of study entry
* No evidence of graft-versus-host-disease (GVHD)
* Adequate organ function, as defined by
* Serum alanine aminotransferase (ALT) ≤5X upper limit of normal (ULN)
* Direct bilirubin ≤ 3X upper limit of normal for age and institution.
* Ejection fraction ≥ 50% or shortening fraction of ≥ 24% on screening echocardiogram.
* Because of the teratogenic effects of venetoclax on developing fetuses, female participants of childbearing potential must have a negative urine or serum HCG prior to study entry and at the start of therapy. All females of childbearing potential must refrain from breastfeeding during study participation, and all male and females of childbearing potential must agree to use an effective form of contraception (abstinence, hormonal, or barrier) prior to study entry, for duration of participation, and for a minimum of 30 days following the last dose of treatment.
* Part I: B-cell or T-cell acute lymphoblastic leukemia (ALL), mixed phenotype acute lymphoblastic leukemia (MPAL) or lymphoblastic lymphoma (LBL) in first or greater relapse or refractory to at least 1 prior remission induction attempt.
* For ALL/MPAL: Bone marrow involvement ≥ 5% by aspirate morphology or ≥ 1% assessable by flow cytometry or validated molecular minimal residual disease (MRD) testing
* For LBL: Radiographically detectable mass or lymph node involvement
* Part II: Histologically confirmed diagnosis of one of the following:
* T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL) in first or greater relapse or refractory to at least 1 prior remission induction attempt.
* For T-ALL: Bone marrow involvement ≥ 5% by aspirate morphology or ≥ 1% assessable by morphology, flow cytometry or validated MRD testing
* For T-LBL (biopsy proven at current or prior relapse): Radiographically detectable mass or lymph node involvement OR
* Relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) with bone marrow involvement ≥1% (assessable by morphology, flow cytometry or validated MRD testing) and at least one of the following characteristics:
* First relapse with adverse biologic determinants as described below:
* KMT2A rearrangement
* Low hypodiploidy, defined as ≤ 40 chromosomes
* t(17;19)
* IKZF1 deletion (without targetable ABL1 fusion)
* Ph-like ALL (without targetable ABL1 fusion)
* Other biologic determinants with adverse prognosis in discussion with the Sponsor-Investigator
* Early first bone marrow relapse occurring \<36 months from initial diagnosis
* Primary refractory ALL that has failed 1 prior induction attempt
* Age: ≥ 1 and ≤ 21 years of age
* Lansky/Karnofsky performance status ≥ 50%
* Participants must have fully recovered from the acute toxic effects of all prior and meet all of the following criteria:
* Myelosuppressive chemotherapy: 14 days, or 5 half-lives, whichever is shorter, must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without a "wash-out" period:
* Standard maintenance therapy: dexamethasone/prednisone, vincristine, 6MP, low dose methotrexate
* Hydroxyurea
* Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine.
* Radiation therapy (XRT):
* Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry
* XRT for chloroma does not require a washout period.
* Palliative XRT does not require a washout
* Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days, or 5 half-lifes, whichever is shorter) must have elapsed since the completion of therapy. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
* Immunotherapy: At least 30 days after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy and checkpoint inhibitors.
* Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
* Prior hematopoietic stem cell transplant (HSCT): Patients who have received HSCT are eligible, but must meet all of the following conditions:
* Allogeneic HSCT \> 90 days of study entry
* No evidence of graft-versus-host-disease (GVHD)
* Adequate organ function, as defined by the following laboratory values:
* Serum alanine aminotransferase (ALT) ≤5X upper limit of normal (ULN), unless deemed secondary to leukemic involvement in discussion with site PI.)
* Direct bilirubin ≤ 3X upper limit of normal for age and institution.
* Serum amylase ≤ 3X institutional ULN .
* Cardiac function as defined as below:
* Ejection fraction ≥ 50% or shortening fraction of ≥ 24% on screening echocardiogram.
* Maximum prior cumulative doxorubicin dose ≤ 360 mg/m2 or equivalent
* Because of the teratogenic effects of venetoclax on developing fetuses, female participants of childbearing potential must have a negative urine or serum HCG prior to study entry and at the start of therapy. All females of childbearing potential must refrain from breastfeeding during study participation, and all male and females of childbearing potential must agree to use an effective non-hormonal form of contraception (abstinence, barrier) prior to study entry, for duration of participation, and for a minimum of 3 months following the last dose of treatment (as calaspargase pegol can render hormonal contraceptives ineffective).
* Use of strong or moderate CYP3A inhibitors/inducers within 3 days of study entry
* Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD
* Individuals with known active hepatitis; baseline testing not required.
* Patients with systemic infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
* Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required.
* Pregnant or nursing women are excluded.
* Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
* Use of strong or moderate CYP3A inhibitors/inducers within 3 days of study entry
* Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD
* Individuals with known active hepatitis; baseline testing not required.
* Patients with systemic infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
* Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required.
* Pregnant or nursing women are excluded.
* Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
* Use of strong or moderate CYP3A inhibitors/inducers within 3 days of study entry
* Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD, or who are less than 90 days from stem cell infusion
* Individuals with known active hepatitis; baseline testing not required.
* Patients with systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
* Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required.
* Pregnant or nursing women are excluded
* Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
* Individuals with a history of allergic reactions to any of the agents being used in this trial, with the exception of pegaspargase or calaspargase pegol. Participants with a history of allergy to pegylated formulation of asparasginase are allowed on study but should receive commercial supply of asparaginase Erwinia chrysanthemi (Erwinaze), crisantaspase (Erwinase), or asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze) instead of calaspargase pegol (see Sections 6.2.6 and 6.2.7). Individuals with a history of allergy to Erwinaze, Erwinase or Rylaze are excluded from the study.
* History of asparaginase-associated pancreatitis.
* Known, active and propagating deep venous thrombus (DVT).
* Individuals with isolated CNS or testicular relapse.
* Presence of surface immunoglobulin by flow cytometry and/or known t(8;14), t(2;8), or t(8;22).
* Individuals with a history of a different malignancy are ineligible except for the following circumstances:
* Individuals are eligible if they have been disease-free for at least 1 year and are deemed by the investigator to be at low risk for recurrence of that malignancy.
* Individuals with the following cancers are eligible if diagnosed and treated within the past year: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Principal Investigator

Andrew E Place, MD, PhD

PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Study Locations (Sites)

University of California San Francisco-Benioff Children's Hospital

San Francisco, California, 94158

United States

Children's Hospital Colorado

Aurora, Colorado, 80045

United States

Children's Healthcare of Atlanta at Arthur M. Blank Hospital

Atlanta, Georgia, 30329

United States

Ann & Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Collaborators and Investigators

Sponsor: Andrew E. Place, MD

Andrew E Place, MD, PhD, PRINCIPAL_INVESTIGATOR, Dana-Farber Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-03-29

Study Completion Date2028-07-02

Study Record Updates

Study Start Date2023-03-29

Study Completion Date2028-07-02

Terms related to this study

Keywords Provided by Researchers

Myelodysplastic Syndrome (MDS)
Treatment-related Acute Myelogenous Leukemia
AML arising from MDS
Relapsed or Refractory Acute Lymphoblastic Leukemia
Relapsed or Refractory Acute Lymphoblastic Lymphoma
Relapsed or Refractory MDS
Treatment-related MDS
Relapsed or Refractory Acute leukemia of ambiguous lineage

Additional Relevant MeSH Terms

Myelodysplastic Syndromes, de Novo
Myelodysplastic Syndromes, Secondary
Myelodysplastic Syndromes, Previously Treated
Treatment-Related Acute Myeloid Leukemia
Therapy-Related Myelodysplastic Syndrome
Acute Lymphoblastic Leukemia, in Relapse
Acute Lymphoblastic Leukemia With Failed Remission
Lymphoblastic Lymphoma, in Relapse
Lymphoblastic Lymphoma, Refractory
Acute Leukemia of Ambiguous Lineage in Relapse
Acute Leukemia of Ambiguous Lineage