Relapsed Childhood ALLNCT05215405
Expanded Access Program of Venetoclax and Navitoclax for Pediatric Patients with Relapsed or Refractory ALL or LL
A study testing Venetoclax and Navitoclax in people with Relapsed Childhood ALL and Relapsed Childhood Lymphoblastic Lymphoma, run by Kathleen Ludwig at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Relapsed Childhood ALL, Relapsed Childhood Lymphoblastic Lymphoma
- What is being tested?
- Venetoclax and Navitoclax
- Type of treatment
- Pill or oral medicine
- How many people
- Not given
- Where
- 1 siteUnited States
- Study dates
- Start not givento not given
- Phase
- Expanded access
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- Child, Adult, Older adult
Who may be able to join
- The subject, parent or guardian must voluntarily sign and date an informed consent.
- 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.
- Subjects must be ≥4 years of age
- Subjects must weight ≥20 kg
- Subjects must have adequate hepatic function:
- ALT and AST ≤5 x ULN and bilirubin ≤1.5 x ULN
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- Subjects must have normal creatinine for age or have a calculated creatinine clearance ≥ 60mL/min/1.73m2
- Subjects must have adequate performance status:
- Subjects ≤ 16 years of age: Lansky ≥ 50,
- Subjects > 16 years of age: Karnofsky ≥ 50 or ECOG <3
- 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.
- Male subjects who are sexually active with women of child bearing potential must agree to use condoms during treatment.
- Female subjects of childbearing potential must have negative results for serum or urine pregnancy test.
Who cannot join
- Subjects who have CNS disease with cranial involvement that requires radiation
- 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.
- Subjects who received any of the following prior to the first dose of investigational drug:
- A strong or moderate CYP3A inhibitor or inducer within 7 days
- Aspirin within 7 days
- Subjects who have active, uncontrolled infection
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- 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.
- Subjects with malabsorption syndrome or any other condition that precludes enteral administration.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
About this study
Official title: 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.
Read the 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)
- Being tested
- Venetoclax, Navitoclax
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
Also called ABT-199
Venetoclax will be administered orally once daily (QD), continuously. Each dose of venetoclax should be taken with approximately 240 mL of water within 30 minutes after the completion of a meal, preferably breakfast.
- Day 1 (200 mg equivalent):
- Patients 20 < 30 kg will take 70 mg
- Patients 30 < 35 kg will take120 mg
- Patients 35 to 45 kg will take 200 mg
- Day 2 onwards (400 mg equivalent):
- Patients 20 < 30 kg will take 170 mg
- Patients 30 < 35 kg will take 250 mg
- Patients 35 to 45 kg will take 400 mg
NavitoclaxDrug
Also called ABT-263
Navitoclax will be administered orally once daily, starting on day 3 of cycle 1 and then may start on day 1 for subsequent cycles. Navitoclax should be taken at the same time each day approximately 24 hours apart. Dosing will be based on the recommended phase II dosing as per the phase I data and subsequent dose recommendations.
- Patients 20 < 45 kg will take 25 mg
- Patients 45 kg or more will take 50 mg
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed Childhood ALLStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Expanded access
Sponsor and investigators
- Lead sponsor
- Kathleen Ludwig
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Kathleen Ludwig, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05215405
- Sponsor's protocol ID
- STU-2021-1222
- Status last verified
- Jan 2025
- First submitted
- 17 Jan 2022
- Last updated
- 3 Feb 2025
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05215405
- Acronym / sponsor ID
- STU-2021-1222
- Study type
- Expanded access
- Recruitment status
- No Longer Available
- Lead sponsor
- Kathleen LudwigUniversity, hospital or other
- First posted
- 31 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- The subject, parent or guardian must voluntarily sign and date an informed consent.
- 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.
- Subjects must be ≥4 years of age
- Subjects must weight ≥20 kg
- Subjects must have adequate hepatic function:
Key exclusion criteria (9 listed)
- Subjects who have CNS disease with cranial involvement that requires radiation
- 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.
- Subjects who received any of the following prior to the first dose of investigational drug:
- Subjects who have active, uncontrolled infection
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VenetoclaxAlso: ABT-199Venetoclax will be administered orally once daily (QD), continuously. Each dose of venetoclax should be taken with approximately 240 mL of water within 30 minutes after the completion of a meal, preferably breakfast. * Day 1 (200 mg equivalent): * Patients 20 < 30 kg will take 70 mg * Patients 30 < 35 kg will take120 mg * Patients 35 to 45 kg will take 200 mg * Day 2 onwards (400 mg equivalent): * Patients 20 < 30 kg will take 170 mg * Patients 30 < 35 kg will take 250 mg * Patients 35 to 45 kg will take 400 mg | Drug | – |
| NavitoclaxAlso: ABT-263Navitoclax will be administered orally once daily, starting on day 3 of cycle 1 and then may start on day 1 for subsequent cycles. Navitoclax should be taken at the same time each day approximately 24 hours apart. Dosing will be based on the recommended phase II dosing as per the phase I data and subsequent dose recommendations. * Patients 20 < 45 kg will take 25 mg * Patients 45 kg or more will take 50 mg | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Venetoclax and Navitoclax in people with Relapsed Childhood ALL and Relapsed Childhood Lymphoblastic Lymphoma, run by Kathleen Ludwig at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.