RECRUITING

Venetoclax and Azacitidine for the Treatment of Acute Myeloid Leukemia in the Post-Transplant Setting

Conditions

Acute Bilineal Leukemia Acute Biphenotypic Leukemia Acute Myeloid Leukemia Mixed Phenotype Acute Leukemia T Acute Lymphoblastic Leukemia Therapy-Related Acute Myeloid Leukemia

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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 phase II trial studies how well venetoclax and azacitidine work for the treatment of acute myeloid leukemia after stem cell transplantation. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax and azacitidine after a stem cell transplant may help control high risk leukemia and prevent it from coming back after the transplant.

Official Title

A Phase II Study of Venetoclax in Combination With Azacitidine in the Post-Transplant Setting for AML, T Cell Leukemia, and Mixed Phenotype Acute Leukemia

Quick Facts

Study Start:2020-05-05

Study Completion:2026-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04128501

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:18 Years to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Participants 18 to 75 years of age. 2. English and non-English speaking patients are eligible. 3. Disease diagnosis with one of the hematological malignancies listed below and who are in morphological remission after allogeneic stem cell transplantation with PBSCs or bone marrow. 1. AML if they had at least one of the following disease characteristics: * Therapy related AML. * Cytogenetics and molecular features consistent with adverse risk group by European LeukemiaNet classification for AML (see Appendix A.). * Primary induction failure defined as absence of complete remission after two different lines of anti-leukemia therapy following diagnosis. * Presence of minimal residual disease by multi-color flow cytometry or cytogenetics or molecular studies at the time of HSCT. * Presence of active disease defined as bone marrow blast count \>5% at the time of HSCT. * Participants transplanted beyond first remission. OR 2. Biphenotypic or bilineage leukemia (including a myeloid component) OR mixed phenotype acute leukemia (MPAL) OR 3. Participants with acute lymphoblastic leukemia; B cell or T cell in original. 4. Participants in morphological remission with no detectable minimal residual disase (MRD) after transplant 5. Participants who are in remission with no detectable minimal residual disease (MRD) after allogeneic stem cell transplant should have: 1. Adequate engraftment within 14 days prior to starting study drug: 2. Absolute neutrophil count (ANC) \>/= 1.0 x 109/L without daily use of myeloid growth factor (G-CSF) for at least 7 days; and, 3. Platelet \>/= 30 x 109/L without platelet transfusion within 1 week 4. Be able to start the drug therapy between 42 to 100 days following HSCT. 6. Use of one of the conditioning regimens as part of allogeneic stem cell transplant listed below: 1. Reduced intensity regimen with fludarabine/melphalan (100-140 mg/m2) with or without TBI with post-transplant Cytoxan OR 2. Myeloablative regimens including: * Busulfan (AUC at or greater than 4000)/fludarabine with post-transplant Cytoxan or total body irradiation (TBI)/etoposide with any graft versus host disease (GVHD) regimen OR * Total body irradiation (TBI)/etoposide with any graft versus host disease (GVHD) regimen. 7. Participants on clinical trials investigating different conditioning regimens (with the above described backbone) with investigational agents will be allowed to enroll. 8. ECOG performance status of 0, 1, or 2. 9. Serum creatinine \</=1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min as defined by the Cockcroft-Gault Equation\* 10. Serum bilirubin \</= 1.5 x upper limit of normal (ULN). 11. Aspartate transaminase (AST) or alanine transaminase (ALT) \</= 2.5 x ULN. 12. Alkaline phosphatase \</= 2.5 x UL. 13. Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. 14. Negative serum or urine pregnancy test for women with reproductive potential. The only subjects who will be exempt from this criterion are postmenopausal women (defined as women who have been amenorrheic for \> 12 months) or subjects who have been surgically sterilized or otherwise proven sterile. 3.1.2. For cohort #3 and cohort #4 patients (MRD positive cohort): 1. Participants 18 to 75 years of age. 2. English and non-English speaking patients are eligible. 3. Disease diagnosis with one of the hematological malignancies listed below and who are in morphological remission after allogeneic stem cell transplantation with PBSCs or bone marrow. a. AML OR b. Biphenotypic or bilineage leukemia (including a myeloid component) or mixed phenotype acute leukemia (MPAL) OR c. Participants with acute lymphoblastic leukemia; B cell or T cell in original. 4. Persistence or reappearance of MRD by flow cytometry or cytogenetic or molecular testing while being in morphological remission after allogeneic stem cell transplantation. 1. When MRD is detected by flow cytometry, disease level at or above the sensitivity level of the test will be required. • MRD level at or above 0.01% for B cell ALL and T cell ALL. 2. When MRD is detected by cytogenetics, disease level at or above the sensitivity level of the test will be required. 3. When MRD is detected by molecular testing, disease level at or above the sensitivity level of the test will be required. • The limited of detection is 0.01% 5. Use of one of the conditioning regimens as part of allogeneic stem cell transplant listed below: * Total body irradiation (TBI)/etoposide with any graft versus host disease (GVHD) regimen. 6. Participants on clinical trials investigating different conditioning regimens (with the above described backbone) with investigational agents will be allowed to enroll. 7. ECOG performance status of 0, 1, or 2. 8. Serum creatinine \</=1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min as defined by the Cockcroft-Gault Equation\* 9. Serum bilirubin \</= 1.5 x upper limit of normal (ULN). 10. Aspartate transaminase (AST) or alanine transaminase (ALT) \</= 2.5 x ULN. 11. Alkaline phosphatase \</= 2.5 x UL. 12. Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. 13. Negative serum or urine pregnancy test for women with reproductive potential. The only participants who will be exempt from this criterion are postmenopausal women (defined as women who have been amenorrheic for \> 12 months) or subjects who have been surgically sterilized or otherwise proven sterile.	1. Active acute GVHD grade II or higher. 2. Active chronic GVHD that is extensive (see Appendix C.). 3. Uncontrolled GVHD (see Appendix C.). 4. Concurrent use of systemic immune suppressive other than calcineurin inhibitors, sirolimus and steroids 5. Active uncontrolled systemic fungal, bacterial or viral infection. 6. Active bleeding. 7. Symptomatic or uncontrolled arrhythmias. 8. Significant active cardiac disease within the previous 6 months, including: 1. New York Heart Association (NYHA) class III or IV congestive heart failure see Appendix C.). 9. Known active viral infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). 10. Prior history of malignancies, other than leukemia, unless the subject has been free of the disease for \>/= 1 year. However, participants with the following history/concurrent conditions are allowed: 1. Basal or squamous cell carcinoma of the skin; 2. Carcinoma in situ of the cervix; 3. Carcinoma in situ of the breast; 4. Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis \[TNM\] clinical staging system). 11. Participants with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures.

Inclusion Criteria

Exclusion Criteria

1. Participants 18 to 75 years of age.
2. English and non-English speaking patients are eligible.
3. Disease diagnosis with one of the hematological malignancies listed below and who are in morphological remission after allogeneic stem cell transplantation with PBSCs or bone marrow.
1. AML if they had at least one of the following disease characteristics:
* Therapy related AML.
* Cytogenetics and molecular features consistent with adverse risk group by European LeukemiaNet classification for AML (see Appendix A.).
* Primary induction failure defined as absence of complete remission after two different lines of anti-leukemia therapy following diagnosis.
* Presence of minimal residual disease by multi-color flow cytometry or cytogenetics or molecular studies at the time of HSCT.
* Presence of active disease defined as bone marrow blast count \>5% at the time of HSCT.
* Participants transplanted beyond first remission. OR
2. Biphenotypic or bilineage leukemia (including a myeloid component) OR mixed phenotype acute leukemia (MPAL) OR
3. Participants with acute lymphoblastic leukemia; B cell or T cell in original.
4. Participants in morphological remission with no detectable minimal residual disase (MRD) after transplant
5. Participants who are in remission with no detectable minimal residual disease (MRD) after allogeneic stem cell transplant should have:
1. Adequate engraftment within 14 days prior to starting study drug:
2. Absolute neutrophil count (ANC) \>/= 1.0 x 109/L without daily use of myeloid growth factor (G-CSF) for at least 7 days; and,
3. Platelet \>/= 30 x 109/L without platelet transfusion within 1 week
4. Be able to start the drug therapy between 42 to 100 days following HSCT.
6. Use of one of the conditioning regimens as part of allogeneic stem cell transplant listed below:
1. Reduced intensity regimen with fludarabine/melphalan (100-140 mg/m2) with or without TBI with post-transplant Cytoxan OR
2. Myeloablative regimens including:
* Busulfan (AUC at or greater than 4000)/fludarabine with post-transplant Cytoxan or total body irradiation (TBI)/etoposide with any graft versus host disease (GVHD) regimen OR
* Total body irradiation (TBI)/etoposide with any graft versus host disease (GVHD) regimen.
7. Participants on clinical trials investigating different conditioning regimens (with the above described backbone) with investigational agents will be allowed to enroll.
8. ECOG performance status of 0, 1, or 2.
9. Serum creatinine \</=1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min as defined by the Cockcroft-Gault Equation\*
10. Serum bilirubin \</= 1.5 x upper limit of normal (ULN).
11. Aspartate transaminase (AST) or alanine transaminase (ALT) \</= 2.5 x ULN.
12. Alkaline phosphatase \</= 2.5 x UL.
13. Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
14. Negative serum or urine pregnancy test for women with reproductive potential. The only subjects who will be exempt from this criterion are postmenopausal women (defined as women who have been amenorrheic for \> 12 months) or subjects who have been surgically sterilized or otherwise proven sterile. 3.1.2. For cohort #3 and cohort #4 patients (MRD positive cohort):
1. Participants 18 to 75 years of age.
2. English and non-English speaking patients are eligible.
3. Disease diagnosis with one of the hematological malignancies listed below and who are in morphological remission after allogeneic stem cell transplantation with PBSCs or bone marrow. a. AML OR b. Biphenotypic or bilineage leukemia (including a myeloid component) or mixed phenotype acute leukemia (MPAL) OR c. Participants with acute lymphoblastic leukemia; B cell or T cell in original.
4. Persistence or reappearance of MRD by flow cytometry or cytogenetic or molecular testing while being in morphological remission after allogeneic stem cell transplantation.
1. When MRD is detected by flow cytometry, disease level at or above the sensitivity level of the test will be required. • MRD level at or above 0.01% for B cell ALL and T cell ALL.
2. When MRD is detected by cytogenetics, disease level at or above the sensitivity level of the test will be required.
3. When MRD is detected by molecular testing, disease level at or above the sensitivity level of the test will be required. • The limited of detection is 0.01%
5. Use of one of the conditioning regimens as part of allogeneic stem cell transplant listed below:
* Total body irradiation (TBI)/etoposide with any graft versus host disease (GVHD) regimen.
6. Participants on clinical trials investigating different conditioning regimens (with the above described backbone) with investigational agents will be allowed to enroll.
7. ECOG performance status of 0, 1, or 2.
8. Serum creatinine \</=1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min as defined by the Cockcroft-Gault Equation\*
9. Serum bilirubin \</= 1.5 x upper limit of normal (ULN).
10. Aspartate transaminase (AST) or alanine transaminase (ALT) \</= 2.5 x ULN.
11. Alkaline phosphatase \</= 2.5 x UL.
12. Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
13. Negative serum or urine pregnancy test for women with reproductive potential. The only participants who will be exempt from this criterion are postmenopausal women (defined as women who have been amenorrheic for \> 12 months) or subjects who have been surgically sterilized or otherwise proven sterile.

1. Active acute GVHD grade II or higher.
2. Active chronic GVHD that is extensive (see Appendix C.).
3. Uncontrolled GVHD (see Appendix C.).
4. Concurrent use of systemic immune suppressive other than calcineurin inhibitors, sirolimus and steroids
5. Active uncontrolled systemic fungal, bacterial or viral infection.
6. Active bleeding.
7. Symptomatic or uncontrolled arrhythmias.
8. Significant active cardiac disease within the previous 6 months, including:
1. New York Heart Association (NYHA) class III or IV congestive heart failure see Appendix C.).
9. Known active viral infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
10. Prior history of malignancies, other than leukemia, unless the subject has been free of the disease for \>/= 1 year. However, participants with the following history/concurrent conditions are allowed:
1. Basal or squamous cell carcinoma of the skin;
2. Carcinoma in situ of the cervix;
3. Carcinoma in situ of the breast;
4. Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis \[TNM\] clinical staging system).
11. Participants with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures.

Contacts and Locations

Study Contact

Betul Oran

CONTACT

713-792-8750

boran@mdanderson.org

Principal Investigator

Betul Oran

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

M D Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Betul Oran, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

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 Date2020-05-05

Study Completion Date2026-12-31

Study Record Updates

Study Start Date2020-05-05

Study Completion Date2026-12-31

Terms related to this study

Additional Relevant MeSH Terms

Acute Bilineal Leukemia
Acute Biphenotypic Leukemia
Acute Myeloid Leukemia
Mixed Phenotype Acute Leukemia
T Acute Lymphoblastic Leukemia
Therapy-Related Acute Myeloid Leukemia