A Phase I Study of Hyper-CVAD In Combination With Venetoclax In Pediatric Patients With Relapsed or Refractory Acute Leukemias That Are of the Lymphoid Lineage Including Bi-Phenotypic or Undifferentiated Leukemias

NCT06466395 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2023-1044NCI-2024-05154
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

To find the recommended dose of hyper-CVAD in combination with venetoclax that can be given to participants with relapsed or refractory leukemia.

Conditions

Bi-Phenotypic Leukemia; Undifferentiated Leukemia; Refractory Acute Leukemia; Relapsed Acute Leukemia

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (2)

Phase 1a

EXPERIMENTAL

Participants enrolled in Phase 1a, the dose of venetoclax the participant receive will depend on when the participant joins this study. The first group of participants will receive the lowest dose level of venetoclax. Each new group will receive a higher dose of venetoclax than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of venetoclax is found. The study doctor will discuss with you the doses the participants will receive as part of hyper-CVAD based on standard of care.

Drug: Venetoclax; Drug: Hyper-CVAD

Phase 1b

EXPERIMENTAL

Participants enrolled in Phase 1b, will receive venetoclax at the recommended dose that was found in Phase 1. The study doctor will discuss with you the doses the participants will receive as part of hyper-CVAD based on standard of care.

Drug: Venetoclax; Drug: Hyper-CVAD

Interventions

Venetoclax DRUG

Given by PO

Also known as: ABT-199, GDC-0199

Phase 1a; Phase 1b

Hyper-CVAD DRUG

Given by IV

Phase 1a; Phase 1b

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Relapsed/refractory leukemias as defined as:
• Pediatric, adolescent, or young adult patients with relapsed or refractory acute leukemias that are of the lymphoid lineage including bi-phenotypic or undifferentiated leukemias as per NCCN v2.2021 and W.H.O. classification in relapse or primary refractory.
• Participants must have ≥5% blasts in the bone marrow as assessed by morphology. However, if an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia with ≥5% blasts in the peripheral blood.
• Participants have adequate performance status (ECOG ≤2) for patients ≥16 years old, Lansky score \>50 for patients \<16 years old.
• Participants must be ≥ 2 years old or less than or equal to 21 years of age at time of signing/or having proxy sign the informed consent to be enrolled on study.
• Participants with asymptomatic CNS disease are eligible.
• These conditions are allowed on study: conditions requiring chronic systemic glucocorticoid use, such as autoimmune disease, graft versus host disease (GVHD) (well controlled on a stable dose of steroid or alternative therapy) or severe asthma. Participants are also allowed up to 5 days of glucocorticoids as cytoreduction, the use of hydroxyurea and the usage of cytarabine up to 2gm/m2. This should also be discussed with PI.
• For participants on chronic glucocorticoid therapy: Participants should be on stable systemic steroid doses less than or equal to 11.6mg/m2 (20 mg max) of prednisone daily
• During times of dexamethasone dosing (cycles 1,3,5 and 7): Hold chronic steroids on days dexamethasone is given then resume normally scheduled chronic steroid dosing the following day.
• Participants on chronic steroids \> 11.6mg/m2 (20 mg max) prednisone equivalent will be excluded from the study.
• The use of topical steroids for cutaneous graft-versus-host disease (GVHD) is allowed.
• Participants should be at least 2 weeks or 5 half-lives (whichever is longer) from prior therapy, other than hydroxyurea, glucocorticoids or low dose cytarabine (as mentioned above) to maintain blast count prior to initiation of study therapy.
• Participants must have adequate organ function and laboratory results (obtained within 14 days of enrollment):
• Total serum bilirubin ≤1.5 x upper limit of normal (ULN). Participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 x ULN.
• Adequate renal function (creatinine clearance \>30mL/min) unless related to the disease.

You may not qualify if:

• Past or current history of a secondary or other primary tumor or a chronic myeloid leukemia (CML) blast crisis with exception of:
• curatively treated non-melanomatous skin cancer,
• other primary solid tumor treated with curative intent and no known active disease present, and no treatment administered during the last 2 years.
• Presence of clinically significant uncontrolled CNS pathology such as epilepsy, paresis, aphasia, stroke, severe brain injuries, organic brain syndrome, or psychosis.
• Presence of the following are allowed: headaches, vomiting, nerve palsy.
• Significant traumatic injury or major surgery (major surgery means opening of a body cavity, e.g., thoracotomy, laparotomy, laparoscopic organ resection, and major orthopedic procedures, e.g. joint replacement, open reduction and internal fixation) within 14 days of scheduled dosing day 1.
• Participants with uncontrolled infections (viral, bacterial, or fungal) per PI's discretion. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable.
• Medical history of cardiovascular disease such as:
• Clinically significant cardiac disease defined as congestive heart failure (NYHA class III or IV), arrhythmia or conduction abnormality requiring medication, or cardiomyopathy. This will be reviewed during screening EKG/ECHO as well as prior documentation.
• Females who are pregnant or lactating.
• Participants may be excluded if they are currently enrolled in another ongoing clinical trial with investigational products.
• Liver cirrhosis or other active severe liver disease or with suspected active alcohol abuse.
• Participants who are unable or unwilling to comply with all study requirements for clinical visits, examinations, tests, and procedures.
• If participant has not recovered from previous chemotherapy, surgery, radiation before the start of study drugs.
• Other severe, uncontrolled 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

venetoclax; CVAD protocol

Study Officials

• David McCall, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David McCall, MD

CONTACT

(713) 792-6604; dmccall1@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2024
• First Posted: June 20, 2024
• Study Start: February 18, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2031
• Last Updated: March 9, 2026

Record last verified: 2026-03

Locations

US (1)