Venetoclax Plus Inotuzumab for B-ALL

NCT05016947 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 21-196
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is evaluating the safety and efficacy of administering venetoclax and inotuzumab ozogamicin in combination in patients with acute lymphoblastic leukemia (ALL) The names of the study drugs involved in this study are:

• Venetoclax
• Inotuzumab ozogamicin
• Dexamethasone

Conditions

ALL; B-cell Acute Lymphoblastic Leukemia; B-Cell Lymphoma

Keywords

B-cell Acute Lymphoblastic Leukemia; B-Cell Lymphoma; ALL

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of venetoclax in combination with inotuzumab ozogamicin

  Descriptive analysis of highest dose of venetoclax that did not cause a dose limiting toxicity with toxicity type based CTCAE vs 5.0 criteria.

  Enrollment to end of treatment up to 9 months

Secondary Outcomes (5)

• Morphologic response

  Enrollment to end of treatment up to 9 months

• Measurable residual disease (MRD)-response

  Enrollment to end of treatment up to 9 months

• Event-free survival (EFS)

  Enrollment to end of treatment up to 9 months

• Disease-free survival (DFS)

  Enrollment to end of treatment up to 9 months

• Overall survival (OS).

  Enrollment to end of treatment up to 9 months

Study Arms (1)

Venetoclax + Inotuzumab Ozogamicin with Dexamethasone

EXPERIMENTAL

Phased 28 day treatment cycles with lead in: Lead In Cycle: Dose escalated venetoclax 1x daily for days 1-3 with and Dexamethasone daily for days 1-3 lead in, 7 days total. Induction Cycle 1: Dose escalated venetoclax 1x daily for days 1-21, Dexamethasone daily for days 1-4, Inotuzumab ozogamicin on days 1, 8, and 15 Induction Cycle 2: Dose escalated venetoclax 1x daily for days and Inotuzumab ozogamicin on days 1, 8, and 15 Consolidation Cycles: Up to 5 cycles of dose escalated Venetoclax 1x daily for days and Inotuzumab ozogamicin on days 1, 8, and 15

Drug: Venetoclax; Drug: Dexamethasone; Drug: Inotuzumab Ozogamicin

Interventions

Venetoclax DRUG

Tablet, taken by mouth

Also known as: Venclexta

Venetoclax + Inotuzumab Ozogamicin with Dexamethasone

Dexamethasone DRUG

Taken orally

Also known as: Decadron, Dexasone, Diodex, Hexadrol, Maxidex

Venetoclax + Inotuzumab Ozogamicin with Dexamethasone

Inotuzumab Ozogamicin DRUG

Intravenous infusion

Also known as: Besponsa

Venetoclax + Inotuzumab Ozogamicin with Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically confirmed CD22+ B-ALL or B-LBL.
• Note: CD22 must be detected on ≥ 20% of lymphoblasts by flow cytometry of peripheral blood, flow cytometry of bone marrow aspirate or tissue biopsy, or immunohistochemistry of the bone marrow or tissue biopsy.
• Note: for R/R disease: ≥ 5% lymphoblasts must be documented in the diagnostic sample (blood, marrow, or tissue biopsy).
• Note: Participants with B-LBL (confirmed CD22-positive extramedullary disease, but none or minimal marrow involvement) are eligible if eligibility criteria otherwise met.
• Note: Participants with Philadelphia-chromosome positive B-ALL are eligible but must be refractory to 2 or more tyrosine kinase inhibitors (TKIs), refractory to ponatinib, or ineligible to receive all available TKIs.
• Note: Participants with chronic myeloid leukemia (CML) in lymphoid blast crisis are eligible but must be refractory to 2 or more TKIs, refractory to ponatinib, or ineligible to receive all available TKIs.
• Participants must have disease that is relapsed or refractory (R/R) to 1 or more cycles of cytotoxic chemotherapy.
• Note: There is no limit to number or type of prior therapies (prior inotuzumab ozogamicin is not permitted).
• Note: Philadelphia-chromosome positive B-ALL patients previously treated with TKI are eligible without receiving cytotoxic chemotherapy if they are unsuitable for standard cytotoxic chemotherapy.
• Participants be aged ≥ 18 years.
• ECOG performance status of 0-3.
• Adequate organ function.
• Serum total bilirubin ≤ 1.5x upper limit of normal (ULN), unless due to Gilbert's syndrome or of non-hepatic origin (i.e. hemolysis).
• ALT and AST ≤ 2.5x ULN, unless clearly due to disease, in which case ≤ 5x ULN is permissible.
• Creatinine clearance of ≥ 30 mL/min calculated using Cockcroft-Gault formula or measured by 24-hour urine collection.

You may not qualify if:

• Absolute blast count of ≥25 K/µL prior to initiation of study treatment. Steroids, hydroxyurea, and/or vincristine may be used to reduce blast count.
• Prior treatment with inotuzumab ozogamicin at any time.
• Prior treatment with venetoclax for relapsed disease; if venetoclax used during first-line therapy, 60 or more days must have elapsed since last dose of venetoclax. Note: The number of patients with prior receipt of venetoclax will be capped at 50% of the participants enrolled in the dose expansion phase.
• Treatment for ALL with chemotherapy within 14 days of first dose of study drugs except for hydroxyurea, steroids, vincristine, and/or intra-thecal chemotherapy.
• Participants with history of decompensated hepatic cirrhosis, veno-occlusive disease (VOD)/sinusoidal obstructive syndrome (SOS), or severe liver disease.
• Patient with uncontrolled intercurrent illness, or severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) except for alopecia.
• Participants who are receiving any other investigational agents.
• Participants receiving any medications or substances within 7 days that are strong CYP3A4 inhibitors (such as fluconazole, voriconazole, posaconazole, isavuconazole, and clarithromycin) or inducers (such as rifampin, rifabutin, phenytoin, carbamazepine, and St. John's Wort) of CY3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference (Appendix C). Of note, anti-fungal azole therapy may be re-introduced after venetoclax dose escalation as outlined in the protocol.
• Participants who have consumed grapefruit, grapefruit products, Seville oranges (used in marmalade), or star fruit within 3 days prior to starting venetoclax.
• Malabsorption syndrome or other conditions (such as inability to swallow pills) that preclude enteral route of venetoclax administration.
• Participants with psychiatric illness/social situations that would limit adherence to study requirements.
• Pregnant women are excluded from this study because the effects of venetoclax and inotuzumab ozogamicin on the developing human fetus are unknown with the potential for teratogenic or abortifacient effects. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax and inotuzumab ozogamicin and therefore breastfeeding should be discontinued.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• AbbVie: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Burkitt Lymphoma; Lymphoma, B-Cell

Interventions

venetoclax; Dexamethasone; Calcium Dobesilate; Inotuzumab Ozogamicin

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Marlise R Luskin, MD, MSCE

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 17, 2021
• First Posted: August 23, 2021
• Study Start: September 24, 2021
• Primary Completion: July 10, 2023
• Study Completion (Estimated): December 23, 2026
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)