A Phase II Study of the Combination of Ponatinib With Mini-hyper CVD Chemotherapy and Venetoclax in Patients With Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia

NCT05268003 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-0802NCI-2022-01686
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The addition of ponatinib to mini-hyper-CVD chemotherapy and venetoclax will improve the complete remission rate in patients with relapsed or refractory T-cell acute lymphoblastic leukemia

Conditions

Acute Lymphoblastic Leukemia; Leukemia

Outcome Measures

Primary Outcomes (1)

• To determine the complete remission (CR) / CR with incomplete count recovery (CRi) rate with the combination of Ponatinib and mini-hyper-CVD chemotherapy and venetoclax.

  through study completion, an average of 1 year

Study Arms (3)

Ponatinib

EXPERIMENTAL

Participants will receive ponatinib (45mg daily) as a single agent for 3 days. These will be called Days -3, -2 and -1

Drug: Ponatinib

Venetoclax

EXPERIMENTAL

Patients will continue venetoclax 400mg daily on days 1-14 of each 28-day cycle.

Drug: Venetoclax

Mini-hyper-CVD

EXPERIMENTAL

Chemotherapy will be administered in the inpatient setting, starting on day 1 of each of the cycles 2-8.

Drug: Mini-hyper CVD

Interventions

Ponatinib DRUG

Given by PO

Ponatinib

Venetoclax DRUG

Given by PO

Venetoclax

Mini-hyper CVD DRUG

Given by IV (vein)

Mini-hyper-CVD

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with relapsed or refractory T-cell acute lymphoblastic leukemia defined as receiving one or more cytotoxic containing regimens and A. Bone marrow involvement with ≥ 5% lymphoblasts B. Age ≥ 12 Years and greater than 40kg
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Adequate organ function
• Serum total bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for participants 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
• Participants must provide written informed consent

You may not qualify if:

• Participant is pregnant or breastfeeding
• Participants under 40kg
• Participants with uncontrolled active 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, dexamethasone, or one dose of cytarabine) prior to starting therapy
• No clinical, radiological or laboratory evidence of pancreatitis, including:
• Serum lipase must be \<2 times the ULN, and
• Serum amylase must be \<2 times the ULN
• Symptomatic or untreated leptomeningeal disease or spinal cord compression. Participants with prior h/o CNS disease are eligible as long as no active CNS disease as documented by recent CSF analysis and/or imaging studies.
• Participants with active heart disease \[New York Heart Association (NYHA) class 3-4 as assessed by history and physical examination, unstable angina/stroke/myocardial infarction within the last 6 months\]
• Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
• Myocardial infarction (MI), stroke, revascularization, unstable angina or transient ischemic attack within 6 months
• Left ventricular ejection fraction (LVEF) less than 50%
• Diagnosed or suspected congenital long QT syndrome

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia

Interventions

ponatinib; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jain Nitin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2022
• First Posted: March 7, 2022
• Study Start: June 7, 2022
• Primary Completion: April 21, 2026
• Study Completion: April 21, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

US (1)