Expanded Access Program of Venetoclax and Navitoclax for Pediatric Patients with Relapsed or Refractory ALL or LL

January 29, 2025 updated by: Kathleen Ludwig

Intermediate Size Expanded Access Program of Venetoclax (ABT-199) in Combination with Navitoclax (ABT-263) for Pediatric Patients with Relapsed or Refractory Acute Lymphocytic Leukemia (ALL) or Lymphoblastic Lymphoma (LL)

The overall goal of this expanded access program is to provide Venetoclax and Navitoclax to patients with acute lymphocytic leukemia (ALL) or lymphoblastic lymphoma (LL) who have exhausted standard treatments.

Study Overview

Status

No longer available

Conditions

Intervention / Treatment

Detailed Description

Acute lymphocytic leukemia (ALL) is a cancer of the immature lymphocytes, a type of white blood cell involved in the body's immune system. People with ALL have lymphocytes that do not mature (lymphoblast). Lymphoblasts replace healthy lymphocytes within the bone marrow and other organs in the lymphatic system.

Lymphoblastic lymphoma (LL) is an aggressive form of non-Hodgkin lymphoma. It is relatively rare, accounting for approximately 2% of all non-Hodgkin lymphomas. In lymphoblastic lymphoma, the abnormal lymphoblasts are present in the lymph nodes or thymus gland, whereas in ALL, the abnormal lymphoblasts are mainly in the blood and bone marrow. Clinically, lymphoblastic lymphoma behaves very similarly to ALL, and the two conditions are often treated with the same regimens.

There have been several recent developments in the treatment of B-ALL, the most common cancer seen in pediatrics. While the cure rate of B-ALL is greater than 90%, children with B-ALL are treated with aggressive chemotherapy regimens that frequently result in long-term toxicities (Oeffinge, Hunger) Furthermore, the patients who experience a relapse have poor outcomes despite treatment with additional chemotherapy often followed by allogeneic stem cell transplant (AlloSCT). The primary predictor of outcome for relapsed B-ALL is the time to relapse; patients who relapse after completing chemotherapy have a cure rate of approximately 50% while those who relapse during treatment have a much lower cure rate of 20-30% (Sun).

Apoptotic pathway targeting therapies, such as navitoclax show promise in the treatment of ALL and LL. Venetoclax +Navitoclax in combination with chemotherapy is well tolerated, with few discontinuations or dose reductions from adverse events (AEs) in patients with relapsed/refractory ALL or LL. The preliminary efficacy of Venetoclax

+Navitoclax was promising in a heavily pretreated population of patients including those with prior SCT or CAR-T, with high rates of Complete response (CR)/complete response with incomplete count recovery (Cri)/complete response with incomplete platelet recovery (CRp), and 10/18 (56%) had undetectable minimal residual disease (MRD). Additional correlative biomarker analyses are ongoing (Pullarkat)

Study Type

Expanded Access

Expanded Access Type

  • Intermediate-size Population
  • Treatment IND/Protocol

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Description

Inclusion Criteria:

  1. The subject, parent or guardian must voluntarily sign and date an informed consent.
  2. Subjects must have relapsed or refractory acute lymphoblastic leukemia (ALL) or relapsed or refractory lymphoblastic lymphoma (LL) and have exhausted available therapies of known benefit for ALL/LL. Refractory is defined as persistent disease after at least 2 courses of chemotherapy.
  3. Subjects must be ≥4 years of age
  4. Subjects must weight ≥20 kg

  5. Subjects must have adequate hepatic function:

    a. ALT and AST ≤5 x ULN and bilirubin ≤1.5 x ULN

  6. Subjects must have normal creatinine for age or have a calculated creatinine clearance ≥ 60mL/min/1.73m2

  7. Subjects must have adequate performance status:

    1. Subjects ≤ 16 years of age: Lansky ≥ 50,
    2. Subjects > 16 years of age: Karnofsky ≥ 50 or ECOG <3
  8. Female subjects of childbearing potential (those who are not postmenopausal for at least 1 year or surgically sterile by bilateral oophorectomy, salpingectomy or hysterectomy) and their male partner must practice as least 1 method of birth control during treatment and through at least 30 days after the last dose of investigational drugs.
  9. Male subjects who are sexually active with women of child bearing potential must agree to use condoms during treatment.
  10. Female subjects of childbearing potential must have negative results for serum or urine pregnancy test.

Exclusion Criteria:

  1. Subjects who have CNS disease with cranial involvement that requires radiation
  2. Subjects who are less than 100 days post-transplant, or >100 days post-transplant with active Graft-versus-host disease (GVHD), or are still continuing post-transplant immunosuppressant therapy within 7 days prior to the first dose of investigational drug.

  3. Subjects who received any of the following prior to the first dose of investigational drug:

    1. A strong or moderate CYP3A inhibitor or inducer within 7 days
    2. Aspirin within 7 days
  4. Subjects who have active, uncontrolled infection
  5. Subjects who have not recovered to less than Common Terminology Criteria for Adverse Events (CTCAE) grade 2 from clinically significant adverse effect(s)/toxicity(s) of previous therapy.
  6. Subjects with malabsorption syndrome or any other condition that precludes enteral administration.
  7. Female subjects who are pregnant or breastfeeding. Male subjects who are considering fathering a child within approximately 30 days or donating sperm during treatment, within approximately 90 days after the last dose of venetoclax/navitoclax.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kathleen Ludwig

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

January 17, 2022

First Submitted That Met QC Criteria

January 17, 2022

First Posted (Actual)

January 31, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 29, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU-2021-1222

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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