Phase Ib/II Trial of Cladribine/Ruxolitinib/Venetoclax in Patients With Relapsed/Refractory T-cell Prolymphocytic Leukemia

NCT07311746 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2025-1464NCI-2025-09671
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if the combination of ruxolitinib with cladribine and venetoclax can help to control the disease in patients with R/R T-PLL.

Conditions

T-cell Prolymphocytic Leukemia; Refractory T-Cell Prolymphocytic 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 (1)

SingleArm: Phase 1b/II - ESC/EXP Treatment with Ruxolitinib + Cladribine + Venetoclax

EXPERIMENTAL

Participants will receive treatment on an inpatient basis for the first cycle and can be administered on an outpatient basis for the subsequent cycles.

Drug: Ruxolitinib; Drug: Cladribine; Drug: Venetoclax

Interventions

Ruxolitinib DRUG

Given orally

Also known as: Jakafi

SingleArm: Phase 1b/II - ESC/EXP Treatment with Ruxolitinib + Cladribine + Venetoclax

Venetoclax DRUG

Taken by mouth

Also known as: Venclexta

SingleArm: Phase 1b/II - ESC/EXP Treatment with Ruxolitinib + Cladribine + Venetoclax

Cladribine DRUG

Given by injection

Also known as: Mavenclad

SingleArm: Phase 1b/II - ESC/EXP Treatment with Ruxolitinib + Cladribine + Venetoclax

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed a diagnosis T-PLL that is relapsed or refractory after prior treatment.
• Age ≥ 18 years.
• Patients must not have had T-PLL directed chemotherapy or antibody therapy for 7 days prior to starting ruxolitinib. However, patients with rapidly proliferative disease may receive hydroxyurea or decadron until 24 hours prior to starting therapy on this protocol.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Adequate organ function as defined below:
• liver function (bilirubin \< 2mg/dL, AST and ALT \<3 x ULN - or ≤5 x ULN if related to leukemic involvement);
• kidney function (estimated creatinine clearance \> 50);
• known cardiac ejection fraction of ≥ 45% within the past 3 months prior to enrolling on the trial;
• Platelet count of ≥ 30,000 (unless determined to be due to disease involvement).
• ECOG performance status of ≤ 2.
• For patients with evidence of chronic HBV infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of HCV infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
• Postmenopausal (no menses in greater than or equal to 12 consecutive months).
• History of hysterectomy or bilateral salpingo-oophorectomy.

You may not qualify if:

• Pregnant women are excluded from this study because the agent used has the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
• Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, clinically significant or cardiac arrhythmia
• Patient with documented hypersensitivity to any of the components of the therapy program.
• Patients with known active, uncontrolled CNS leukemia will not be eligible.
• Patients with prior treatment with a JAK1, JAK2, or JAK3 inhibitor will not be eligible.
• Men and women of childbearing potential who do not practice contraception.
• Known history of active HIV infection (HIV 1/2 antibodies).
• Active HBV or HCV infection that requires treatment or at risk for HBV reactivation.
• Hepatitis B virus DNA and HCV RNA must be undetectable upon testing. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. Prior test results obtained as part of standard of care that confirm a subject is immune and not at risk for reactivation (ie, hepatitis B surface antigen negative, surface antibody positive) may be used for purposes of eligibility and tests do not need to be repeated. Subjects with prior positive serology results must have negative polymerase chain reaction results. Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment.
• Patients who are receiving any other investigational agents.
• Patients with psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Prolymphocytic, T-Cell

Interventions

ruxolitinib; Cladribine; venetoclax

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Tapan Kadia, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tapan Kadia, MD

CONTACT

(713) 563-3534; tkadia@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: December 29, 2025
• First Posted: December 31, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): January 31, 2031
• Last Updated: December 31, 2025

Record last verified: 2025-12

Locations

US (1)