Venetoclax and Chemotherapy as Frontline Therapy in Older Patients and Patients With Relapsed/Refractory ALL

NCT ID: NCT03319901

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-30
• Study Completion Date: 2027-04-30

Brief Summary

This research study is studying a medication called Venetoclax and a chemotherapy regimen as a possible treatment for Acute Lymphoblastic Leukemia.

The drugs involved in this study are:

• Venetoclax
• Standard Chemotherapy (which includes cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, 6-mercaptopurine, etoposide, and cytarabine

Detailed Description

This research study is a Phase I clinical trial, which tests the safety of an investigational drug and drug combination and also tries to define the appropriate dose of the investigational drug and drug combination to use for further studies. "Investigational" means that the drug and drug combination is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved Venetoclax for this specific disease, but it has been approved for other uses.

Venetoclax is an inhibitor of Bcl-2. Bcl-2 is critical for keeping cancer cells alive.

By inhibiting Bcl-2, venetoclax promotes cancer cell death. This drug is currently being used in other clinical trials for people with certain types of leukemia, lymphoma, and multiple myeloma. There is some evidence from those and other laboratory trials that venetoclax may kill cancer cells and cause tumors to shrink.

In this research study, the investigators are investigating how safe the combination of Venetoclax and standard chemotherapy is and how it affects this disease.. The participant will be given Venetoclax alone first and the standard chemotherapies will be given in combination. This study aims to provide information to help determine the dose of Venetoclax , in combination with standard chemotherapy, affects this disease the best and which dose is the safest.

Conditions

Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Venetoclax + Chemotherapy

• Venetoclax is administered orally once daily for 21 days in each cycle
• Standard Chemotherapy will be administered every 28 days

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Venetoclax is an inhibitor of Bcl-2. Bcl-2 is critical for keeping cancer cells alive.

By inhibiting Bcl-2, venetoclax promotes cancer cell death.

Standard Chemotherapy

Intervention Type: DRUG

Standard treatment of chemotherapy is administered

Interventions

Venetoclax

Venetoclax is an inhibitor of Bcl-2. Bcl-2 is critical for keeping cancer cells alive.

By inhibiting Bcl-2, venetoclax promotes cancer cell death.

Intervention Type: DRUG

Standard Chemotherapy

Standard treatment of chemotherapy is administered

Intervention Type: DRUG

Other Intervention Names

ABT199

Eligibility Criteria

Inclusion Criteria

• Patients with previously untreated acute lymphoblastic leukemia (B-cell or T-cell)
• Bone marrow involvement with ≥20% lymphoblasts
• Age ≥ 60 Years

OR

• Patients with relapsed or refractory acute lymphoblastic leukemia (B-cell or T-cell) defined as receiving one or more cytotoxic containing regimens
• Bone marrow involvement with ≥5% lymphoblasts
• Age ≥ 18 Years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Refer to Appendix D)
• Adequate organ function

• Serum total bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert's disease
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN, unless clearly due to disease involvement
• Creatinine clearance >50 mL/min (calculated according to institutional standards or using Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formula)
• Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use an effective contraception method during the study and for 30 days following the last dose of study drug. Women of non- childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
• Patients or their legally authorized representative must provide written informed consent

Exclusion Criteria

• Ph-positive ALL, Burkitt's leukemia/lymphoma, or lymphoblastic lymphoma
• Patient is pregnant or breastfeeding
• Patients with uncontrolled infection
• Hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
• Major surgery or radiation therapy within 4 weeks prior to the first study dose
• Systemic chemotherapy/radiotherapy/investigational therapy within 14 days (with the exception of hydroxyurea and/or dexamethasone, or one dose of cytarabine) prior to starting therapy
• Symptomatic or untreated leptomeningeal disease or spinal cord compression
• Patients with active heart disease (New York Heart Association (NYHA) class 3-4 as assessed by history and physical examination, unstable angina/stroke/myocardial infarction within the last 6 months)
• Patients with a cardiac ejection fraction (as measured by either Multi Gated Acquisition (MUGA) or echocardiogram (EKG)) <40%
• History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses)
• Concurrent use of warfarin
• Received Cytochrome P450 3A (CYP3A) inhibitors (such as fluconazole, ketoconazole, voriconazole, and clarithromycin) within 3 days of starting venetoclax; received strong CYP3A inducers (such as rifampin, rifabutin, phenytoin, carbamazepine, and St. John's Wort) within 3 days of starting venetoclax
• Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax
• Prior treatment with venetoclax
• Malabsorption syndrome or other conditions that preclude enteral route of administration
• Other 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Marlise Luskin, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marlise Luskin, MD, MSCE

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

University of Chicago

Chicago, Illinois, United States

Site Status: RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status: RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

Intermountain LDS Hospital

Salt Lake City, Utah, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Marlise Luskin, MD, MSCE

Role: CONTACT

Marlise_Luskin@DFCI.HARVARD.EDU

617-632-1909

Rebecca Leonard

Role: CONTACT

Rebecca_leonard@dfci.harvard.edu

Facility Contacts

Wendy Stock, MD

Role: primary

wstock@medicine.bsd.uchicago.edu

Hanno R Hock, MD, PhD

Role: primary

Marlise Luskin, MD, MSCE

Role: primary

Marlise_Luskin@DFCI.HARVARD.EDU

617-632-1906

Marlise Luskin, MD, MSCE

Role: backup

MLUSKIN@PARTNERS.ORG

617-632-1906

Nitin Jain, MD

Role: primary

njain@mdanderson.org

713-745-6080

Julie Asch, MD

Role: primary

References

Luskin MR, Shimony S, Keating J, Winer ES, Garcia JS, Stone RM, Jabbour E, Flamand Y, Stevenson K, Ryan J, Zeng Z, Letai A, Konopleva M, Jain N, DeAngelo DJ. Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemia. Blood Adv. 2025 Feb 11;9(3):617-626. doi: 10.1182/bloodadvances.2024014405.

Reference Type: DERIVED

PMID: 39546748 (View on PubMed)

Other Identifiers

16-648

Identifier Type: -

Identifier Source: org_study_id