Active — Not RecruitingPhase 2

Cladribine With Simultaneous or Delayed Rituximab to Treat Hairy Cell Leukemia

United States175 participantsStarted 2008-10-20

Plain-language summary

Background: Hairy cell leukemia (HCL) is highly responsive to but not curable by cladribine (CdA). HCL responds to rituximab, which is not yet standard therapy for HCL. Patients with the interleukin 2 (IL-2) receptor (CD25)-negative hairy cell leukemia variant (HCLv) respond poorly to initial cladribine but do respond to rituximab in anecdotal reports. Deoxycytidine kinase phosphorylates cladribine to chlorodeoxyadenosine triphosphate (CdATP), which incorporates into deoxyribonucleic acid (DNA), leading to DNA strand breaks and inhibition of DNA synthesis. Rituximab is an anti-cluster of differentiation 20 (CD20) monoclonal antibody which induces apoptosis and either complement or antibody dependent cytotoxicity (antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). Patients in complete remission (CR) to cladribine have minimal residual disease (MRD) by immunohistochemistry of the bone marrow biopsy (BMBx IHC), a risk for early relapse. Tests for HCL MRD in blood or marrow include flow cytometry fluorescence-activated cell sorting (FACS) or polymerase chain reaction (PCR) using consensus primers. The most sensitive HCL MRD test is real-time quantitative PCR using sequence-specific primers real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR). In studies with limited follow-up, MRD detected by tests other than RQ-PCR can be eliminated by rituximab after cladribine in greater than 90 percent of patients, but MRD rates after cladribine alone are unknown. Simultaneous cladribine and rituximab might be superior or inferior to delaying rituximab until detection of MRD. Only 4 HCL-specific trials are listed on Cancer.gov: a phase II trial of cladribine followed 4 weeks later by 8 weekly doses of rituximab, and phase I-II trials of recombinant immunotoxins targeting cluster of differentiation-22 (CD22) (BL22, HA22) and CD25 (LMB-2). Objectives: Primary: To determine if HCL MRD differs at 6 months after cladribine with or without rituximab administered concurrently with cladribine. Secondary: * To compare cladribine plus rituximab vs cladribine alone in terms of 1) initial MRD-free survival and disease-free survival, and 2) response to delayed rituximab for relapse, to determine if early rituximab compromises later response. * To determine if MRD levels and tumor markers (soluble CD25 and CD22) after cladribine and/or rituximab correlate with response and clinical endpoints. * To determine, using MRD and tumor marker data, when bone marrow biopsy (BMBx) can be avoided. * To compare response and MRD after the 1st and 2nd courses of cladribine. * To evaluate the effects of cladribine and rituximab on normal T- and B-cells. * To enhance the study of HCL biology by cloning, sequencing and characterizing monoclonal immunoglobulin rearrangements. Eligibility: HCL with 0-1 prior courses of cladribine and treatment indicated. Design: Cladribine 0.15 mg/Kg/day times 5 doses each by 2hour(hr) intravenous (i.v.) infusion (days 1-5) Rituximab 375 mg/m\^2/week times 8 weeks, randomized half to begin day 1, then repeat for all patients with blood-MRD relapse at least 6 months after cladribine. Also, may repeat for those with blood-MRD relapse at least 6 months after delayed rituximab. MRD tests used for the primary objective will be limited to BMBx IHC, blood FACS or blood consensus PCR, all Clinical Laboratory Improvement Amendments (CLIA) certified. Blood MRD relapse is defined as FACS positivity or low blood counts (ANC less than 1500/microl, platelet (Plt) less than 100,000/microl, or hemoglobin (Hgb) less than 11). Stratification: 68 patients with 0 and 62 with 1 prior course of cladribine. Statistics: 80% power to discriminate rates of MRD of 5 vs 25%, or 10 vs 35% Non-randomized arm: 20 with HCLv will begin rituximab with cladribine. Accrual Ceiling: 152 patients (130 HCL, 2 extra HCL if needed, and 20 HCLv.)

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

* INCLUSION CRITERIA: Evidence of Hairy Cell Leukemia (HCL) by flow cytometry, reviewed by the Laboratory of Pathology, National Cancer Institute (NCI), including positivity for Cluster of Differentiation 19 (CD19), Cluster of Differentiation 22 (CD22), cluster of differentiation 20 (CD20), and integrin alpha X (CD11c). Bone marrow biopsy (BMBx) consistent with HCL, reviewed by Laboratory of Pathology, NCI. BMBx may be negative in hairy cell leukemia variant, (HCLv) in patients with increasing peripheral blood HCLv cells and spleen size. Treatment indicated based on demonstration of at least one of the following, no more than 4 weeks from the time of enrollment, and no less than 6 months after prior purine analog and no less than 4 weeks after other prior treatment, if applicable. * Neutropenia (absolute neutrophil count (ANC) less than 1000 cells/microl). * Anemia (hemoglobin (Hgb) less than 10g/dL). * Thrombocytopenia (Platelet (Plt) less than 100,000/microl). * Absolute lymphocyte count (ALC) of greater than 5,000 cells/microL * Symptomatic splenomegaly. * Enlarging lymph nodes greater than 2cm. * Repeated infections requiring oral or intravenous (i.v.) antibiotics. * Patients who have eligible blood counts within 4 weeks from enrollment will not be considered ineligible if subsequent blood counts prior to enrollment fluctuate and become ineligible up until the time of enrollment. No prior purine analog therapy except up to 1 prior course of cladribine. No prior ritu…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Response Rate Comparing Minimal Residual Disease (MRD) at 6 Months After Start of Treatment in Comparison Groups

Timeframe: Restaged 6 months after the start of treatment

Trial details

NCT IDNCT00923013

SponsorNational Cancer Institute (NCI)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2024-07-15

Results submitted2025-06-27

View on ClinicalTrials.gov More Hairy Cell Leukemia trials