Hairy Cell LeukemiaPhase 2NCT00923013
Cladribine With Simultaneous or Delayed Rituximab to Treat Hairy Cell Leukemia
A Phase 2 study testing Cladribine, Rituximab and BMbx in people with Hairy Cell Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hairy Cell Leukemia
- What is being tested?
- Cladribine, Rituximab and BMbx
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 175 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Oct 2008to 31 Jan 2030
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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 rituximab unless HCLv patient.
- Eastern Cooperative Oncology Group (ECOG) performance status (78) of 0-3.
- Patients must be able to understand and give informed consent.
- Women of child-bearing age and all men must use birth control of any type until at least 12 months after the last dose of therapy.
- Creatinine less than or equal to 1.5 or creatinine clearance greater than or equal to 60 ml/ml.
- Bilirubin less than or equal to 2 unless consistent with Gilbert's (total/direct greater than 5), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 times upper limits of normal.
- No other therapy (i.e. chemotherapy, interferon) for 4 weeks prior to study entry, or cladribine for 6 months prior to study entry.
- Age at least 18
- Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months after completion of treatment.
- Subject has provided written informed consent
- Patients must be willing to co-enroll in the investigators companion protocol 10-C-0066 titled Collection of Human Samples to Study Hairy Cell and other Leukemias, and to Develop Recombinant Immunotoxins for Cancer Treatment.
Who cannot join
- Presence of active untreated infection
- Uncontrolled coronary disease or New York Heart Association Classification (NYHA) class III-IV heart disease.
- Known infection with HIV. Hepatitis B is allowed only if viral load is undetectable and if on anti-hepatitis B therapy like Entecavir. Hepatitis C is allowed only if viral load is undetectable, and if the patient has received curative therapy.
- Patients with documented history of no response to cladribine, and without 50% improvement in platelets, hemoglobin or granulocytes. This exclusion does not apply to HCLv. These patients are eligible regardless of prior response to chlorodeoxyadenosine (CDA)
- Pregnant or lactating women.
- Presence of active 2nd malignancy requiring treatment. 2nd malignancies with low activity which do not require treatment (i.e. low-grade prostate cancer, basal cell or squamous cell skin cancer) do not constitute exclusions.
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- Inability to comply with study and/or follow-up procedures.
- Presence of central nervous system (CNS) disease, which is symptomatic.
- At the Investigators discretion, receipt of a live vaccine within 4 weeks prior to randomization. Efficacy and/or safety of immunization during periods of B-cell depletion have not been adequately studied. It is recommended that a patients vaccination record and possible requirements be reviewed. Per the investigator's discretion, the patient may have any required vaccination/booster administered at least 4 weeks prior to the initiation of study treatment. Review of the patient s immunization status for the following vaccinations is recommended: tetanus; diphtheria; influenza; pneumococcal polysaccharide; Varicella; measles, mumps and rubella (MMR); and hepatitis B. Patients who are considered to be at high risk for hepatitis B virus (HBV) infection and for whom the investigator has determined that immunization is indicated should complete the entire HBV vaccine series at least 4 weeks prior to participation in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Randomized Trial of Cladribine (CdA) With Simultaneous or Delayed Rituximab to Eliminate Hairy Cell Leukemia Minimal Residual Disease
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.
Read more
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.)
Read the detailed description
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.
Purine analogs cladribine and pentostatin have similar efficacy for HCL, both inhibiting deoxyribonucleic acid (DNA) synthesis selectively in HCL cells. Cladribine is effective after just 1 cycle. 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 > 90% of patients, but MRD rates after purine analog 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).
Objective:
To determine if HCL MRD differs at 6 months after cladribine with or without rituximab administered concurrently with cladribine.
Eligibility:
HCL with 0-1 prior courses of cladribine or pentostatin 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, and
bone marrow aspirate FACS, all Clinical Laboratory Improvement Amendments (CLIA) certified. Blood MRD relapse is defined as FACS positivity or low blood counts (absolute neutrophil count (ANC) less than 1500/microl, platelet (Plt) less than 100,000/microl, or hemoglobin (Hgb) less than 11) attributed to HCL. Patients FACS-negative in both blood and bone marrow aspirate are considered MRD-negative complete response (CR) regardless of blood counts.
Randomization: 68 HCL patients with 0 and 62 with 1 prior course of purine analog
Statistics: 80% power to discriminate rates of MRD of 5 vs. 25%, or 10 vs. 35%
Non-randomized HCLv arm: 20 patients with HCLv will begin rituximab with cladribine.
Non-randomized HCL arm: 25 newly diagnosed patients will be enrolled to receive rituximab
beginning day 1, but beginning before the 1st dose of cladribine, rather than after.
Accrual ceiling: 175 evaluable patients (155 HCL and 20 HCLv)
- Conditions
- Hairy Cell Leukemia
- Being tested
- Cladribine, Rituximab, BMbx, MRI, EKG
- Keywords
- Hairy Cell Leukemia, Cladribine, Rituximab, Minimal Residual Disease, Leukemia
- Medical subject headings
- Leukemia, Hairy Cell, Neoplasm, Residual, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CladribineDrug
Also called Mavenclad
Cladribine 0.15 mg/Kg/day by 2-hour intravenous (i.v.) infusion days 1-5. The infusion time may be changed to 1 hour at the discretion of the principal investigator (PI).
RituximabDrug
Also called Rituxan
Rituximab 375 mg/m^2 intravenous (i.v.) infusion every week x8, begin day 1 in half of randomized patients and in all hairy cell leukemia variant (HCLv) patients, and then again in all patients at least 6 months later when hairy cell leukemia (HCL) is detected by blood fluorescence-activated cell sorting (FACS).
BMbxProcedure or surgery
Also called Bone marrow biopsy
Baseline and week 5.
MRIDiagnostic test
Also called Magnetic resonance imaging
Baseline and week 5.
EKGDiagnostic test
Also called Electrocardiogram
Baseline and week 5.
EchocardiogramDiagnostic test
Also called Echo
Baseline.
Abdominal/splenic ultrasoundDiagnostic test
Also called Abdominal/splenic U/S
Baseline and week 5.
Stress testProcedure or surgery
Baseline.
| Study group | Role | What they receive |
|---|---|---|
| 1/Cladribine with immediate Rituximab | Experimental | Cladribine with immediate Rituximab. Receives: Drug: Cladribine; Drug: Rituximab; Procedure: BMbx; Diagnostic Test: MRI; Diagnostic Test: EKG; Diagnostic Test: Echocardiogram; Diagnostic Test: Abdominal/splenic ultrasound; Procedure: Stress test |
| 2/Cladribine with Rituximab Delayed by at Least 6 months After Cladribine | Active comparator | Cladribine with Rituximab delayed by at least 6 months after Cladribine if and when minimal residual disease is detected. Receives: Drug: Cladribine; Drug: Rituximab; Procedure: BMbx; Diagnostic Test: MRI; Diagnostic Test: EKG; Diagnostic Test: Echocardiogram; Diagnostic Test: Abdominal/splenic ultrasound; Procedure: Stress test |
| 3/Non-randomized Group Receiving Cladribine with Immediate Rituximab | Experimental | Non-randomized group receiving Cladribine with immediate Rituximab (before rather than after the 1st of the 5 daily doses of cladribine on day 1). Receives: Drug: Cladribine; Drug: Rituximab; Procedure: BMbx; Diagnostic Test: MRI; Diagnostic Test: EKG; Diagnostic Test: Echocardiogram; Diagnostic Test: Abdominal/splenic ultrasound; Procedure: Stress test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate Comparing Minimal Residual Disease (MRD) at 6 Months After Start of Treatment in Comparison Groups
Participants with newly diagnosed Hairy Cell Leukemia (HCL) and once relapsed HCL were split and both groups were randomized to receive either simultaneous treatment with Cladribine and Rituxan or Cladribine with Rituxan given no earlier than 6 months after cladribine as needed. Outcome measured by Bone Marrow and Blood Flow cytometry and histochemistry of the core biopsy at the 6 months after start of treatment time point. If all three were negative for hairy cells participants were in a minimal residual disease status (MRD). And were considered without HCL disease at that time point.
Measured: Restaged 6 months after the start of treatment
Secondary outcomes (1)
Minimal Residual Disease (MRD)-Free Survival After Cladribine and up to 2 Courses of Rituximab
Compare Cladribine + Rituxan vs cladribine alone in terms of MRD-free survival. MRD free survival time is the time until relapsing from MRD to -free to Complete response. Measured by blood and bone marrow flow cytometry, complete blood count (CBC), and bone marrow immunohistochemistry.
Measured: Testing done 6 months post first dose of treatment, then yearly x2 years and then every 2 years after cladribine indefinitely
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2009 (estimated)
- Study start20 Oct 2008
- Primary completion15 Jul 2024
- Study completion31 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Hairy Cell LeukemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 175 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Robert Kreitman, M.D., National Cancer Institute (NCI)
- Investigators
- Robert J Kreitman, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00923013
- Sponsor's protocol ID
- 090005
- Other IDs
- 09-C-0005
- Status last verified
- Jul 2026
- First submitted
- 17 Jun 2009
- Last updated
- 18 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
Publications
Bouroncle BA. Thirty-five years in the progress of hairy cell leukemia. Leuk Lymphoma. 1994;14 Suppl 1:1-12.
PubMed 7820038Kreitman RJ, Cheson BD. Malignancy: Current Clinical Practice: Treatment of Hairy Cell Leukemia at the Close of the 20th Century. Hematology. 1999;4(4):283-303. doi: 10.1080/10245332.1999.11746452.
PubMed 11399570Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.
PubMed 17237035Chihara D, Arons E, Stetler-Stevenson M, Yuan C, Wang HW, Zhou H, Raffeld M, Xi L, Steinberg SM, Feurtado J, James-Echenique L, Tai CH, Patel KP, Braylan RC, Calvo KR, Maric I, Dulau-Florea A, Kreitman RJ. Long term follow-up of a phase II study of cladribine with concurrent rituximab with hairy cell leukemia variant. Blood Adv. 2021 Dec 14;5(23):4807-4816. doi: 10.1182/bloodadvances.2021005039.
PubMed 34607348Chihara D, Arons E, Stetler-Stevenson M, Yuan CM, Wang HW, Zhou H, Raffeld M, Xi L, Steinberg SM, Feurtado J, James L, Wilson W, Braylan RC, Calvo KR, Maric I, Dulau-Florea A, Kreitman RJ. Randomized Phase II Study of First-Line Cladribine With Concurrent or Delayed Rituximab in Patients With Hairy Cell Leukemia. J Clin Oncol. 2020 May 10;38(14):1527-1538. doi: 10.1200/JCO.19.02250. Epub 2020 Feb 28.
PubMed 32109194
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Cladribine (CdA) With Simultaneous or Delayed Rituximab to Eliminate Hairy Cell Leukemia Minimal Residual Disease
- ClinicalTrials.gov ID
- NCT00923013
- Acronym / sponsor ID
- 090005
- Conditions
- Hairy Cell Leukemia
- Keywords
- Hairy Cell Leukemia, Cladribine, Rituximab, Minimal Residual Disease, Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 175 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 20 Oct 2008 (actual)
- Primary completion
- 15 Jul 2024 (actual)
- Study completion
- 31 Jan 2030 (estimated)
- First posted
- 18 Jun 2009 (estimated)
- Results
- Posted 8 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.)
Detailed description
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.
Purine analogs cladribine and pentostatin have similar efficacy for HCL, both inhibiting deoxyribonucleic acid (DNA) synthesis selectively in HCL cells. Cladribine is effective after just 1 cycle. 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 > 90% of patients, but MRD rates after purine analog 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).
Objective:
To determine if HCL MRD differs at 6 months after cladribine with or without rituximab administered concurrently with cladribine.
Eligibility:
HCL with 0-1 prior courses of cladribine or pentostatin 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, and
bone marrow aspirate FACS, all Clinical Laboratory Improvement Amendments (CLIA) certified. Blood MRD relapse is defined as FACS positivity or low blood counts (absolute neutrophil count (ANC) less than 1500/microl, platelet (Plt) less than 100,000/microl, or hemoglobin (Hgb) less than 11) attributed to HCL. Patients FACS-negative in both blood and bone marrow aspirate are considered MRD-negative complete response (CR) regardless of blood counts.
Randomization: 68 HCL patients with 0 and 62 with 1 prior course of purine analog
Statistics: 80% power to discriminate rates of MRD of 5 vs. 25%, or 10 vs. 35%
Non-randomized HCLv arm: 20 patients with HCLv will begin rituximab with cladribine.
Non-randomized HCL arm: 25 newly diagnosed patients will be enrolled to receive rituximab
beginning day 1, but beginning before the 1st dose of cladribine, rather than after.
Accrual ceiling: 175 evaluable patients (155 HCL and 20 HCLv)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1/Cladribine with immediate Rituximab | Experimental | Drug: Cladribine, Drug: Rituximab, Procedure: BMbx, Diagnostic Test: MRI, Diagnostic Test: EKG, Diagnostic Test: Echocardiogram, Diagnostic Test: Abdominal/splenic ultrasound, Procedure: Stress testCladribine with immediate Rituximab. |
| 2/Cladribine with Rituximab Delayed by at Least 6 months After Cladribine | Active comparator | Drug: Cladribine, Drug: Rituximab, Procedure: BMbx, Diagnostic Test: MRI, Diagnostic Test: EKG, Diagnostic Test: Echocardiogram, Diagnostic Test: Abdominal/splenic ultrasound, Procedure: Stress testCladribine with Rituximab delayed by at least 6 months after Cladribine if and when minimal residual disease is detected. |
| 3/Non-randomized Group Receiving Cladribine with Immediate Rituximab | Experimental | Drug: Cladribine, Drug: Rituximab, Procedure: BMbx, Diagnostic Test: MRI, Diagnostic Test: EKG, Diagnostic Test: Echocardiogram, Diagnostic Test: Abdominal/splenic ultrasound, Procedure: Stress testNon-randomized group receiving Cladribine with immediate Rituximab (before rather than after the 1st of the 5 daily doses of cladribine on day 1). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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).
Key exclusion criteria (9 listed)
- Presence of active untreated infection
- Uncontrolled coronary disease or New York Heart Association Classification (NYHA) class III-IV heart disease.
- Known infection with HIV. Hepatitis B is allowed only if viral load is undetectable and if on anti-hepatitis B therapy like Entecavir. Hepatitis C is allowed only if viral load is undetectable, and if the patient has received curative therapy.
- Patients with documented history of no response to cladribine, and without 50% improvement in platelets, hemoglobin or granulocytes. This exclusion does not apply to HCLv. These patients are eligible regardless of prior response to chlorodeoxyadenosine (CDA)
- Pregnant or lactating women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CladribineAlso: MavencladCladribine 0.15 mg/Kg/day by 2-hour intravenous (i.v.) infusion days 1-5. The infusion time may be changed to 1 hour at the discretion of the principal investigator (PI). | Drug | 1/Cladribine with immediate Rituximab, 2/Cladribine with Rituximab Delayed by at Least 6 months After Cladribine, 3/Non-randomized Group Receiving Cladribine with Immediate Rituximab |
| RituximabAlso: RituxanRituximab 375 mg/m^2 intravenous (i.v.) infusion every week x8, begin day 1 in half of randomized patients and in all hairy cell leukemia variant (HCLv) patients, and then again in all patients at least 6 months later when hairy cell leukemia (HCL) is detected by blood fluorescence-activated cell sorting (FACS). | Drug | 1/Cladribine with immediate Rituximab, 2/Cladribine with Rituximab Delayed by at Least 6 months After Cladribine, 3/Non-randomized Group Receiving Cladribine with Immediate Rituximab |
| BMbxAlso: Bone marrow biopsyBaseline and week 5. | Procedure or surgery | 1/Cladribine with immediate Rituximab, 2/Cladribine with Rituximab Delayed by at Least 6 months After Cladribine, 3/Non-randomized Group Receiving Cladribine with Immediate Rituximab |
| MRIAlso: Magnetic resonance imagingBaseline and week 5. | Diagnostic test | 1/Cladribine with immediate Rituximab, 2/Cladribine with Rituximab Delayed by at Least 6 months After Cladribine, 3/Non-randomized Group Receiving Cladribine with Immediate Rituximab |
| EKGAlso: ElectrocardiogramBaseline and week 5. | Diagnostic test | 1/Cladribine with immediate Rituximab, 2/Cladribine with Rituximab Delayed by at Least 6 months After Cladribine, 3/Non-randomized Group Receiving Cladribine with Immediate Rituximab |
| EchocardiogramAlso: EchoBaseline. | Diagnostic test | 1/Cladribine with immediate Rituximab, 2/Cladribine with Rituximab Delayed by at Least 6 months After Cladribine, 3/Non-randomized Group Receiving Cladribine with Immediate Rituximab |
| Abdominal/splenic ultrasoundAlso: Abdominal/splenic U/SBaseline and week 5. | Diagnostic test | 1/Cladribine with immediate Rituximab, 2/Cladribine with Rituximab Delayed by at Least 6 months After Cladribine, 3/Non-randomized Group Receiving Cladribine with Immediate Rituximab |
| Stress testBaseline. | Procedure or surgery | 1/Cladribine with immediate Rituximab, 2/Cladribine with Rituximab Delayed by at Least 6 months After Cladribine, 3/Non-randomized Group Receiving Cladribine with Immediate Rituximab |
Primary outcome
Response Rate Comparing Minimal Residual Disease (MRD) at 6 Months After Start of Treatment in Comparison Groups
Time frame: Restaged 6 months after the start of treatment
Participants with newly diagnosed Hairy Cell Leukemia (HCL) and once relapsed HCL were split and both groups were randomized to receive either simultaneous treatment with Cladribine and Rituxan or Cladribine with Rituxan given no earlier than 6 months after cladribine as needed. Outcome measured by Bone Marrow and Blood Flow cytometry and histochemistry of the core biopsy at the 6 months after start of treatment time point. If all three were negative for hairy cells participants were in a minimal residual disease status (MRD). And were considered without HCL disease at that time point.
1 secondary outcome
Minimal Residual Disease (MRD)-Free Survival After Cladribine and up to 2 Courses of Rituximab
Time frame: Testing done 6 months post first dose of treatment, then yearly x2 years and then every 2 years after cladribine indefinitely
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 7820038Bouroncle BA. Thirty-five years in the progress of hairy cell leukemia. Leuk Lymphoma. 1994;14 Suppl 1:1-12.
- Background: PubMed 11399570Kreitman RJ, Cheson BD. Malignancy: Current Clinical Practice: Treatment of Hairy Cell Leukemia at the Close of the 20th Century. Hematology. 1999;4(4):283-303. doi: 10.1080/10245332.1999.11746452.
- Background: PubMed 17237035Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.
- Derived from this study: PubMed 34607348Chihara D, Arons E, Stetler-Stevenson M, Yuan C, Wang HW, Zhou H, Raffeld M, Xi L, Steinberg SM, Feurtado J, James-Echenique L, Tai CH, Patel KP, Braylan RC, Calvo KR, Maric I, Dulau-Florea A, Kreitman RJ. Long term follow-up of a phase II study of cladribine with concurrent rituximab with hairy cell leukemia variant. Blood Adv. 2021 Dec 14;5(23):4807-4816. doi: 10.1182/bloodadvances.2021005039.
- Derived from this study: PubMed 32109194Chihara D, Arons E, Stetler-Stevenson M, Yuan CM, Wang HW, Zhou H, Raffeld M, Xi L, Steinberg SM, Feurtado J, James L, Wilson W, Braylan RC, Calvo KR, Maric I, Dulau-Florea A, Kreitman RJ. Randomized Phase II Study of First-Line Cladribine With Concurrent or Delayed Rituximab in Patients With Hairy Cell Leukemia. J Clin Oncol. 2020 May 10;38(14):1527-1538. doi: 10.1200/JCO.19.02250. Epub 2020 Feb 28.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert J Kreitman, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cladribine, Rituximab and BMbx in people with Hairy Cell Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Rate Comparing Minimal Residual Disease (MRD) at 6 Months After Start of Treatment in Comparison Groups (time frame: Restaged 6 months after the start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00923013, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.