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

NCT06863259 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IoVeX-JR-2024
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

B-cell Acute Lymphoblastic Leukemia

Keywords

Relapsed; B-ALL; B-cell Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  4 years

Study Arms (1)

IoVeX

EXPERIMENTAL

Drug: Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone

Interventions

Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone DRUG

Subjects will receive a course of inotuzumab ozogamicin administered by central venous catheter over 60 minutes on days 1, 8, and 15. Venetoclax (by mouth or NG) and dexamethasone (by mouth, NG, or IV) are given daily per assigned dose level. Venetoclax and dexamethasone are started 2 days prior to inotuzumab to limit risk of tumor lysis syndrome with a two-day venetoclax ramp up in cycle 1. On days 1 and 8, venetoclax administration should be scheduled for 4 hours after the beginning of inotuzumab ozogamicin administration. If the patient is not able to ingest venetoclax at the scheduled time, it may still be given later in the day, but efforts should be made to administer the venetoclax within 2 hours of the scheduled time whenever possible.

IoVeX

Eligibility Criteria

• Age: 1 Year - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis:
• \- Patients must have relapsed B-ALL \> 5 % bone marrow blasts with or without extramedullary disease.
• 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:
• nd 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.
• Prior Therapy:
• \- Cytotoxic chemotherapy:
• At least 14 days must have elapsed from the completion of systemic cytotoxic therapy that is known to be myelosuppressive with the exception of hydroxyurea for cytoreduction OR conventional maintenance chemotherapy (i.e., corticosteroids, vincristine, 6MP, and/or oral methotrexate) for patient who relapse while on maintenance therapy OR lumbar puncture with intrathecal chemotherapy. Corticosteroids, vincristine, 6MP, and/or oral methotrexate must be discontinued at least 24 hours prior to the start of protocol therapy. If corticosteroids were used to modify immune adverse events of prior therapy rather than as chemotherapy, at least 14 days must have elapsed since the last dose.
• Systemic corticosteroids may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy. For all patients, corticosteroids may be administered as a premedication for inotuzumab ozogamicin and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency.
• At least seven days must have elapsed from the administration of anti-cancer agents not known to be myelosuppressive.
• Anti-cancer agents that are antibodies
• At least 21 days must have elapsed from infusion of last dose of antibody. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days.

You may not qualify if:

• 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.
• Concomitant Medications:
• 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).
• Infection:
• 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.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma; Recurrence

Interventions

Inotuzumab Ozogamicin; venetoclax; Dexamethasone

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Jeremy Rubinstein, MD, PhD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeremy Rubinstein, MD, PhD

CONTACT

513-636-2799; jeremy.rubinstein@cchmc.org

Site Primary Contact Cancer line

CONTACT

513-636-2799; cancer@cchmc.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone (IoVeX)

Study Record Dates

• First Submitted: March 3, 2025
• First Posted: March 7, 2025
• Study Start: May 21, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF

Locations

US (1)