RECRUITING

Study of Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone for Relapsed B-cell ALL

Conditions

B-cell Acute Lymphoblastic Leukemia Relapsed B-ALL

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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

The goal of this clinical trial is to learn if the combination of drugs Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone (IoVeX) are safe to treat relapsed B-cell Acute Lymphoblastic Leukemia (B-ALL) in pediatric and adult patients. It will also learn if these drugs are well tolerated. The main questions it aims to answer are: Is the drug combination of Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone (IoVeX) safe when given to patients? What medical problems do patients taking IoVeX experience? Participants will: Receive this combination of drugs for 1 cycle which is 28 days at various timepoints. If participants tolerate cycle 1 they will be eligible to continue to cycle 2 which is also 28 days. Have checkups and tests at the beginning of the study and throughout the course of each cycle.

Official Title

A Phase 1 Study With a Pilot Expansion Phase of Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone (IoVeX) for Relapsed B-cell Acute Lymphoblastic Leukemia (B-ALL)

Quick Facts

Study Start:2025-05-21

Study Completion:2029-01-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06863259

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 39 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* At least 20% of leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by flow cytometry of a bone marrow aspirate. In the case of an inadequate aspirate sample (dry tap) or if bone marrow aspirate is unable to be obtained due to patient clinical status, then flow cytometry of peripheral blood specimens may be substituted if the patient has \> 1,000/µL circulating blasts. Alternatively, CD22 expression may be documented by immunohistochemistry of a relapse bone marrow biopsy specimen. * Patients with one of the following: * 2nd or greater relapse OR first relapse less than 24 months from diagnosis OR first or greater relapse in patients over 18. * Primary refractory disease: defined as \> 1% bone marrow blasts by flow MRD after at least 2 courses of frontline chemotherapy. Patients who receive 2 courses of chemotherapy and 1 course of blinatumomab are also eligible, but no further treatment attempts beyond that are permitted. * Any relapse after HSCT or CAR-T therapy. * Patients with Ph+ ALL must have had at least two prior therapy attempts and failed all available tyrosine kinase inhibitors. * Anti-cancer agents that are antibodies * Radiation therapy * Hematopoietic stem cell transplant * Chimeric antigen receptor T-cell therapy * Prior Inotuzumab ozogamicin Patients with prior InO exposure must have received no more than 2.1 mg/m2 of prior InO and be at least 90 days from last dose. * Prior Venetoclax exposure • Patients with prior venetoclax exposure are eligible provided they are at least 30 days from last dose. * Adequate Renal Function Defined As: * Adequate Liver Function Defined As: * Direct bilirubin ≤ 1.5 x upper limit of normal (ULN) for age. * SGPT (ALT) \< 2.5 x the age-appropriate upper limit of normal (ULN) per local lab (unless elevation is related to leukemia involvement). * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.	* Patients with any prior history of SOS irrespective of severity. * Patients with isolated CNS, testicular, or any other isolated extramedullary site of relapse. * Patients with CNS3 disease at time of enrollment regardless of marrow involvement. * Investigational drugs: patients who are currently receiving another investigational drug. * Anti-cancer agents: Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy, and intrathecal chemotherapy). * Anti-GVHD or agents to prevent organ rejection post-transplant. Patients who are receiving cyclosporine, tacrolimus, or other agents to prevent either graft vs host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. At least 3 half-lives must have relapsed after the last dose of GVHD or anti-rejection medications. * Patients \> 10 kg AND \> 24months may receive azole antifungals (See altered venetoclax dosing provided for patients on azoles). * Patients with known HIV, hepatitis B or C infections. Testing to prove negative status is not required for enrollment unless it is deemed necessary for usual medical care of the patient. * Patients who have an active uncontrolled infection defined as: * Positive bacterial blood culture within 48 hours of study enrollment. * Fever above 38.2℃ within 48 hours of study enrollment with documented infection Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability. * A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection. * Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with C. difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed, and stools must have normalized to baseline. * Active viral or protozoal infection requiring IV treatment. * Patients known to have one of the following concomitant genetic syndromes: Blood syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachmann-Diamond syndrome, or any other known bone marrow failure syndrome. * There have been no human studies of inotuzumab ozogamicin or venetoclax in pregnant women. Based on safety studies, both agents have the potential to impair human male and female fertility to adversely affect human embryo-fetal development. Women of childbearing potential should be advised to avoid becoming pregnant while receiving inotuzumab ozogamicin and venetoclax. There is no known information regarding the presence of inotuzumab ozogamicin or venetoclax in human milk, the effects on the breast-fed infant, or the effect on milk production. Women should not breast-feed during treatment with inotuzumab ozogamicin or venetoclax and for at least 2 months after the final dose. Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment. * Female patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of their study participation and for 8 months after the last dose of inotuzumab ozogamicin or venetoclax. * Men with female partners of childbearing potential should use effective contraception during treatment with inotuzumab ozogamicin and venetoclax and for at least 5 months after the last dose of inotuzumab ozogamicin and venetoclax. * Lactating females are not eligible unless they agree not to breastfeed their infants. * Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 2) with the exception of alopecia. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to venetoclax or inotuzumab ozogamicin.

Inclusion Criteria

Exclusion Criteria

* At least 20% of leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by flow cytometry of a bone marrow aspirate. In the case of an inadequate aspirate sample (dry tap) or if bone marrow aspirate is unable to be obtained due to patient clinical status, then flow cytometry of peripheral blood specimens may be substituted if the patient has \> 1,000/µL circulating blasts. Alternatively, CD22 expression may be documented by immunohistochemistry of a relapse bone marrow biopsy specimen.
* Patients with one of the following:
* 2nd or greater relapse OR first relapse less than 24 months from diagnosis OR first or greater relapse in patients over 18.
* Primary refractory disease: defined as \> 1% bone marrow blasts by flow MRD after at least 2 courses of frontline chemotherapy. Patients who receive 2 courses of chemotherapy and 1 course of blinatumomab are also eligible, but no further treatment attempts beyond that are permitted.
* Any relapse after HSCT or CAR-T therapy.
* Patients with Ph+ ALL must have had at least two prior therapy attempts and failed all available tyrosine kinase inhibitors.
* Anti-cancer agents that are antibodies
* Radiation therapy
* Hematopoietic stem cell transplant
* Chimeric antigen receptor T-cell therapy
* Prior Inotuzumab ozogamicin Patients with prior InO exposure must have received no more than 2.1 mg/m2 of prior InO and be at least 90 days from last dose.
* Prior Venetoclax exposure • Patients with prior venetoclax exposure are eligible provided they are at least 30 days from last dose.
* Adequate Renal Function Defined As:
* Adequate Liver Function Defined As:
* Direct bilirubin ≤ 1.5 x upper limit of normal (ULN) for age.
* SGPT (ALT) \< 2.5 x the age-appropriate upper limit of normal (ULN) per local lab (unless elevation is related to leukemia involvement).
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

* Patients with any prior history of SOS irrespective of severity.
* Patients with isolated CNS, testicular, or any other isolated extramedullary site of relapse.
* Patients with CNS3 disease at time of enrollment regardless of marrow involvement.
* Investigational drugs: patients who are currently receiving another investigational drug.
* Anti-cancer agents: Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy, and intrathecal chemotherapy).
* Anti-GVHD or agents to prevent organ rejection post-transplant. Patients who are receiving cyclosporine, tacrolimus, or other agents to prevent either graft vs host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. At least 3 half-lives must have relapsed after the last dose of GVHD or anti-rejection medications.
* Patients \> 10 kg AND \> 24months may receive azole antifungals (See altered venetoclax dosing provided for patients on azoles).
* Patients with known HIV, hepatitis B or C infections. Testing to prove negative status is not required for enrollment unless it is deemed necessary for usual medical care of the patient.
* Patients who have an active uncontrolled infection defined as:
* Positive bacterial blood culture within 48 hours of study enrollment.
* Fever above 38.2℃ within 48 hours of study enrollment with documented infection Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability.
* A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection.
* Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with C. difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed, and stools must have normalized to baseline.
* Active viral or protozoal infection requiring IV treatment.
* Patients known to have one of the following concomitant genetic syndromes: Blood syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachmann-Diamond syndrome, or any other known bone marrow failure syndrome.
* There have been no human studies of inotuzumab ozogamicin or venetoclax in pregnant women. Based on safety studies, both agents have the potential to impair human male and female fertility to adversely affect human embryo-fetal development. Women of childbearing potential should be advised to avoid becoming pregnant while receiving inotuzumab ozogamicin and venetoclax. There is no known information regarding the presence of inotuzumab ozogamicin or venetoclax in human milk, the effects on the breast-fed infant, or the effect on milk production. Women should not breast-feed during treatment with inotuzumab ozogamicin or venetoclax and for at least 2 months after the final dose. Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment.
* Female patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of their study participation and for 8 months after the last dose of inotuzumab ozogamicin or venetoclax.
* Men with female partners of childbearing potential should use effective contraception during treatment with inotuzumab ozogamicin and venetoclax and for at least 5 months after the last dose of inotuzumab ozogamicin and venetoclax.
* Lactating females are not eligible unless they agree not to breastfeed their infants.
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 2) with the exception of alopecia.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to venetoclax or inotuzumab ozogamicin.

Contacts and Locations

Study Contact

Jeremy Rubinstein, MD, PhD

CONTACT

513-636-2799

jeremy.rubinstein@cchmc.org

Site Primary Contact Cancer line

CONTACT

513-636-2799

cancer@cchmc.org

Principal Investigator

Jeremy Rubinstein, MD, PhD

PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Study Locations (Sites)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229

United States

Collaborators and Investigators

Sponsor: Children's Hospital Medical Center, Cincinnati

Jeremy Rubinstein, MD, PhD, PRINCIPAL_INVESTIGATOR, Children's Hospital Medical Center, Cincinnati

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 Date2025-05-21

Study Completion Date2029-01-01

Study Record Updates

Study Start Date2025-05-21

Study Completion Date2029-01-01

Terms related to this study

Keywords Provided by Researchers

Relapsed
B-ALL
B-cell Acute Lymphoblastic Leukemia

Additional Relevant MeSH Terms

B-cell Acute Lymphoblastic Leukemia