A Phase 1, Open-Label, Sequential Cross-over, Bioavailability/Bioequivalence Study to Compare the Pharmacokinetics of Oral Cladribine With the Reference Listed Drug, Intravenous Cladribine

NCT06021600 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 2023-0134NCI-2023-06805
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

To compare an investigational oral form of the drug cladribine to the FDA approved form of the drug when it is given by vein (IV).

Conditions

Leukemia; Myelodysplastic Syndromes; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 (3)

Cohort 1 (Pilot)

EXPERIMENTAL

Participants will only receive 1 dose of oral cladribine, followed by 4 daily doses of cladribine by vein

Drug: Cladribine

Cohort 2 (PK)

EXPERIMENTAL

Participants will only receive 1 dose of oral cladribine, followed by 4 daily doses of cladribine by vein

Drug: Cladribine

Cohort 3 (All-Oral HCL)

EXPERIMENTAL

Participants will all receive the same dose of oral cladribine over the course of 5 days.

Drug: Cladribine

Interventions

Cladribine DRUG

Given by PO and Given by IV (vein)

Also known as: Leustatin®, 2-CdA

Cohort 1 (Pilot); Cohort 2 (PK); Cohort 3 (All-Oral HCL)

Eligibility Criteria

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

You may qualify if:

• Patients, both men and women of all races and ethnic groups, aged ≥ 18 years are eligible for enrollment.
• Provision of written informed consent prior to any study related procedures.
• Patients with newly diagnosed or previously treated HCL who have indication for therapy and are candidates for cladribine therapy (all 3 cohorts).
• Patients with previously treated T-cell prolymphocytic leukemia who have received at least one course of alemtuzumab-based treatment, who have documented indication for therapy and who are candidates for cladribine therapy (Cohort 1 and 2) only.
• Adequate renal and hepatic organ function as indicated by the following laboratory values:
• Creatinine clearance ≥ 60 mL/min
• Serum total bilirubin ≤1.5×ULN (with the exception of patients with known Gilbert's syndrome: serum total bilirubin must be \<3×ULN in these patients)
• Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) ≤2.5×ULN or ≤5×ULN if due to leukemic involvement).
• Adequate cardiac function with a left ventricular ejection fraction ≥45%.
• Female patients are eligible to enter and participate in the study if they are of non-childbearing potential. Female patients of childbearing age must have a negative pregnancy test at screening and must not be breastfeeding and also agree to use at least 2 forms of effective birth control during the study treatment period and for at least 3 months after the last dose of investigational product. (See definitions in Appendix 2)
• Male patients are eligible to enter and participate in the study if they agree to use effective methods of contraception during the study treatment period and for at least 3 months after the last dose of investigational product. (See definitions in Appendix 2)

You may not qualify if:

• Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, malabsorption, or psychiatric illness/social situations that would limit compliance with study requirements.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the compounds in the study.
• Receipt of live or live-attenuated vaccines within 4-6 weeks preceding oral cladribine treatment, planned during cladribine treatment or after cladribine treatment until the participant's immune system is no longer weakened (e.g., white blood cell counts are within normal limits).
• Active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody at screening. Patients who are hepatitis C antibody positive will need to have a negative PCR result prior to enrollment. Those who are hepatitis C PCR positive will be excluded. Patients who are hepatitis B virus surface antigen positive or hepatitis B PCR positive will be excluded. Patients who are anti-HBc antibody positive and who are surface antigen negative will need to have a negative PCR result before enrollment.
• Human immunodeficiency virus (HIV) positive with a viral load \>400 copies/mL and a CD4+ T-cell count of \<350 cells/µL or with a history of an acquired immunodeficiency syndrome (AIDS) opportunistic infection within the past 12 months.
• Legal incapacity or limited legal capacity.
• Inability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening or otherwise altering the product formulation.
• Patients unwilling to comply with protocol requirements related to the assigned cohort.
• Patients with baseline QTc \>470 msec will not be enrolled in Cohort 1. If QTc changes are observed in response to cladribine in Cohort 1, then the protocol will be amended to exclude patients with baseline QTc \>470 msec from Cohorts 2 and 3, as well

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Cladribine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid

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

• Farhad Ravandi-Kashani, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 28, 2023
• First Posted: September 1, 2023
• Study Start: October 9, 2023
• Primary Completion: March 24, 2026
• Study Completion: March 24, 2026
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

US (1)