Combining Venetoclax with chemotherapy for treating older patients and those with relapsed Acute Lymphoblastic Leukemia

A Phase Ib Study of the Combination of Venetoclax With Chemotherapy as Frontline Therapy in Older Patients and Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia

This study is testing if combining a new drug called Venetoclax with standard chemotherapy can help older patients and those with relapsed Acute Lymphoblastic Leukemia feel better and improve their treatment outcomes.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 82 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Dana-Farber Cancer Institute (Academic / other)
• Drugs / interventions: chemotherapy, radiation, methotrexate, cyclophosphamide, doxorubicin
• Locations: 5 sites (Chicago, Illinois and 4 other locations)
• Trial ID: NCT03319901 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of Venetoclax, an investigational drug, in combination with standard chemotherapy for patients with Acute Lymphoblastic Leukemia (ALL). The study includes older patients and those with relapsed or refractory ALL, aiming to determine the optimal dosage of Venetoclax alongside established chemotherapy agents. Participants will first receive Venetoclax alone, followed by the chemotherapy regimen, to assess how well this combination works against the disease. The trial is designed to gather data that could inform future treatment protocols for ALL.

Who should consider this trial

Good fit: Ideal candidates include patients aged 60 and older with untreated ALL or those aged 18 and older with relapsed or refractory ALL.

Not a fit: Patients with other types of leukemia or those who do not meet the specific eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could provide a new effective option for patients with Acute Lymphoblastic Leukemia, particularly those who are older or have relapsed disease.

How similar studies have performed: Other studies have shown promising results with Venetoclax in different leukemia contexts, suggesting potential for success in this novel application.

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

Where this trial is running

Chicago, Illinois and 4 other locations

• University of Chicago — Chicago, Illinois, United States (Recruiting)
• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• Intermountain LDS Hospital — Salt Lake City, Utah, United States (Recruiting)

Study contacts

• Principal investigator: Marlise Luskin, MD, MSCE — Dana-Farber Cancer Institute
• Study coordinator: Marlise Luskin, MD, MSCE

Conditions Leukemia