M16-106: Combination Chemotherapy for Relapsed Acute Lymphoblastic Leukemia

Phase I Study of Venetoclax with Navitoclax and Chemotherapy for Relapsed Acute Lymphoblastic Leukemia

Category:

Leukemia / Lymphoma

Diseases Treated:

Acute lymphoblastic leukemia

Eligibility Overview:

  • Acute lymphoblastic leukemia (ALL) that has not responded to treatment or has come back after treatment
  • Between 4 and 45 years old
  • Weigh at least 20 kg (44 lbs)
  • Able to swallow pills

 

 

  1. Brief Summary

    Long-term survival rates for children and adults with relapsed or refractory acute lymphoblastic leukemia (ALL) are poor. This Phase I study will evaluate two investigational drugs to treat this patient population: venetoclax and navitoclax.

    Venetoclax is a selective inhibitor of B cell lymphoma 2 (BCL-2). Navitoclax is an inhibitor of BCL-2 and the related protein BCL-XL. Both agents help restore the process of apoptosis by binding directly to target proteins, displacing pro apoptotic proteins, triggering mitochondrial outer membrane permeabilization, and the activation of caspases. Preclinical studies using these agents have shown promising results in targeting ALL.

    Primary Objectives

    • Evaluate the safety of venetoclax in combination with navitoclax
    • Evaluate the safety of venetoclax in combination with navitoclax and chemotherapy
    • Determine dose-limiting toxicities of venetoclax, navitoclax and chemotherapy
    • Assess the pharmacokinetics of venetoclax in combination with navitoclax

    Eligibility Criteria

    Inclusion criteria include:

    • Refractory or relapsed acute lymphoblastic leukemia (ALL)
    • Between 4 and 45 years old
    • Weigh at least 20 kg (44 lbs)
    • Able to swallow pills
    • Adequate liver function
    • Lansky performance status ≥50 (16 years old and younger) or Karnofsky performance status ≥50 (older than 16 years)

    Exclusion Criteria include:

    • Overt CNS disease (CNS3 status)
    • Fewer than 100 days post-transplant, or greater than 100 days post-transplant with active GVHD, or are continuing post-transplant immunosuppressant therapy within 7 days prior to first dose of study drug
    • Received any of the following prior to first dose of study drug:
      • A biologic agent for anti-neoplastic intent within 30 days
      • CAR-T infusion or other cellular therapy within 30 days
      • Anti-cancer therapy, including blinatumomab, chemotherapy, radiation therapy, targeted small molecule agents or investigational agents within 14 days, or 5 half-lives, whichever is shorter
    • Pregnant or breast-feeding

    Study Sites

    St. Jude Children’s Research Hospital, Memphis, Tennessee
    Collaborating sites in the U.S.

  2. About this study

    Acute lymphoblastic leukemia (ALL) normally responds to treatment very well.  However, in some patients, the cancer comes back after treatment (relapsed) or does not get better with treatment (refractory). When this happens, the cancer is harder to treat.

    This study will test two experimental drugs, combined with chemotherapy, to treat aggressive ALL in children and adults. The drugs are called venetoclax and navitoclax. These drugs block certain proteins that can help cancer cells stay alive.

    Venetoclax has been approved by some regulatory authorities to treat other cancers but it is not approved for use in combination with navitoclax. It is not approved to treat ALL that is relapsed or refractory.

    Purpose of this clinical trial

    The main goal of this clinical trial is to find out the highest, safest dose of the combination of venetoclax and navitoclax that can be safely given with chemotherapy. Researchers also want to learn the good and bad effects of this treatment.

    Eligibility overview

    • Acute lymphoblastic leukemia (ALL) that has not responded to treatment or come back after treatment
    • Between 4 and 45 years old 
    • Weigh at least 20 kg (44 lbs)
    • Able to swallow pills
  3. M16-106 Quick View
    Sponsors AbbVie
    ClinicalTrials.gov identifier NCT03181126
    Trial Start Date November 2017
    Estimated Enrollment 42
    Study Type Interventional
    Study Phase Phase I
    Conditions Acute lymphoblastic leukemia   
    Ages Between 4 and 45 years old
    Principal investigator Jeffrey Rubnitz, MD, PhD
    Study Sites St. Jude Children’s Research Hospital and collaborating sites in  the U.S.
    For a consultation or to discuss M16-106 St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

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