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

NCT03319901 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 16-648
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 5

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

Conditions

Leukemia

Keywords

Leukemia

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  To determine the maximum tolerated dose (MTD) of venetoclax in combination with chemotherapy in patients with newly diagnosed Acute Lymphoblastic Leukemia (ALL)

  2 years

Secondary Outcomes (16)

• To Evaluate The Safety of the Combination

  2 years

• Complete Response

  2 years

• Progression Free Survival

  2 years

• Overall Survival

  2 years

• Minimal Residual Disease

  2 years

Study Arms (1)

Venetoclax + Chemotherapy

EXPERIMENTAL

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

Drug: Venetoclax; Drug: Standard Chemotherapy

Interventions

Venetoclax 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.

Also known as: ABT199

Venetoclax + Chemotherapy

Standard Chemotherapy DRUG

Standard treatment of chemotherapy is administered

Venetoclax + Chemotherapy

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (5)

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Intermountain LDS Hospital

Salt Lake City, Utah, 84143, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 39546748 DERIVED

MeSH Terms

Conditions

Leukemia

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Marlise Luskin, MD, MSCE

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marlise Luskin, MD, MSCE

CONTACT

617-632-1909; Marlise_Luskin@DFCI.HARVARD.EDU

Rebecca Leonard

CONTACT

Rebecca_leonard@dfci.harvard.edu

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: September 28, 2017
• First Posted: October 24, 2017
• Study Start: October 30, 2017
• Primary Completion: April 30, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: June 5, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)