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Active, not recruitingNCT01059786Updated Jul 22, 2026Results posted

Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia

A Phase 2 interventional study of Pentostatin and Rituximab in Hairy Cell Leukemia, sponsored by National Cancer Institute (NCI). Active, not recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-22.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
69
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Background:

  • Researchers are attempting to develop new treatments for hairy cell leukemia (HCL) that has not responded well to or has recurred after standard HCL therapies. One nonstandard treatment for HCL is rituximab, an antibody that binds to the cancer cells and helps the immune system destroy them. By combining rituximab with other anti-cancer drugs, researchers hope to determine whether the combined drugs are successful in treating HCL.
  • Pentostatin and bendamustine are two anti-cancer drugs that have been used to treat different kinds of blood and immune system cancers. Bendamustine is approved to treat other kinds of leukemia and lymphoma, but it has not been used to treat HCL. Pentostatin has been used for more than 20 years to treat HCL, but it has not been combined with rituximab in official clinical trials.

Objectives:

  • To determine whether rituximab with either pentostatin or bendamustine is a more effective treatment for HCL than rituximab alone.
  • To determine whether pentostatin or bendamustine is a more effective treatment for HCL when combined with rituximab.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with hairy cell leukemia that has not responded well to or has relapsed after standard HCL therapies.

Design:

  • The study will last for four treatment cycles of 28 days each.
  • Prior to the study, participants will be screened with a full medical history and physical exam, bone marrow biopsy (if one has not been performed in the last 6 months), computed tomography (CT) or ultrasound scan, tumor measurements, and other tests as required by the researchers. Participants will provide blood and urine samples at this time as well.
  • Rituximab with bendamustine: Participants will receive rituximab on Days 1 and 15 of each cycle and bendamustine on Days 1 and 2 of each cycle, for a total of four cycles.
  • Rituximab with pentostatin: Participants will receive rituximab on Days 1 and 15 of each cycle and pentostatin on rituximab on Days 1 and 15 of each cycle, for a total of four cycles.
  • Participants will have regular tests during the treatment cycles, including bone marrow biopsies and CT or ultrasound scans. Participants will also provide regular blood and urine samples to assess the results of treatment.
Read the detailed description

Background:

  • Hairy cell leukemia (HCL) is highly responsive to purine analogs cladribine and pentostatin, without evidence of cure. Neither is standard after 2 courses, due to cumulative marrow and T-cell toxicity and declining remission rates and durations. Once resistant, patients after multiple relapses can die of disease-related cytopenias.
  • Rituximab alone in 51 patients from 5 trials who had cytopenias and at least 1 prior purine analog resulted in 10 complete + 10 partial remissions (complete response (CR) + partial response (PR) = overall response rate (ORR 39%).
  • Rituximab with cladribine gives high CR rates in 1st or 2nd line but is not standard.
  • While cladribine use is more common for 1st and 2nd line, pentostatin is often used for subsequent treatment because of \< 100% cross-resistance.
  • Retrospective published data for pentostatin plus rituximab in HCL include 7 of 7 responses with 6 (86%) CRs, and there are no prospective data.
  • Recombinant immunotoxins targeting cluster of Differentiation 25 (CD25) (LMB-2) and cluster of differentiation-22 (CD22) (CAT-3888 (BL22) and R490A (HA22) are highly active in purine analog resistant HCL. Palliative pentostatin-rituximab is often used off-protocol for patients with immunogenicity needing more therapy.
  • Bendamustine is approved for early treatment of chronic lymphocytic leukemia (CLL) and is effective with rituximab for relapsed/refractory CLL. Its use in HCL is unreported.
  • CRs with minimal residual disease (MRD) by immunohistochemistry (IHC) of bone marrow biopsy (BMBx IHC), can relapse early. 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 MRD test in HCL is real-time quantitative PCR using sequence-specific primers (real-time quantitative polymerase chain reaction (RQ-PCR).
  • Of 5 HCL-specific trials listed on Cancer.gov, 2 are phase II trials of cladribine + rituximab in 1st and 2nd line (1 randomized at National Institutes of Health (NIH), 1 non-randomized at MDA), and 3 NIH phase I-II trials of recombinant immunotoxins BL22, HA22 and LMB-2.

Objectives:

-Primary:

--To determine if pentostatin + rituximab and bendamustine + rituximab are each associated with adequate response rates (ORR=PR+CR) in patients with relapsed HCL, and, if so, to select which combination is likely to be superior.

Eligibility:

  • HCL needing therapy, either greater than or equal to 2 prior courses of purine analog, 1 course purine analog plus greater than or equal to 1 course rituximab if \< 1 year response to the 1 course purine analog, diagnosis of HCL variant (HCLv), or unmutated immunoglobulin heavy variable 4-34 (IGHV4-34+) expressing HCL/HCLv.
  • Prior treatment, ineligibility for, or patient refusal of recombinant immunotoxin.

Design:

  • Rituximab 375 mg/m\^2 on day 1, 15 for 6 x 28-day cycles (all 72 patients).
  • Initial tolerability study: 12 patients receive rituximab + bendamustine (nonrandom), including 6 at 70 mg/m\^2 and 6 at 90 mg/m\^2 of bendamustine.
  • Randomize: 1) 28 patients to bendamustine 90 mg/m\^2/day, days 1 and 2 each cycle 2) 28 patients to pentostatin 4 mg/m\^2 days 1 and 15 of each cycle.
  • Non-randomized: up to 4 patients to receive either bendamustine 90 mg/m\^2P2P/day, days 1 and 2 each cycle or pentostatin 4 mg/m\^2P2P days 1 and 15 of each cycle.
  • Statistics: If > 14/28 respond, can conclude with 90% power that response > 40% in that arm. >80% probability of selecting the better arm if true response probability is approximately 40-50% on the inferior arm and >15% higher on the superior arm.
  • Stratify to equalize the % of patients/arm refractory to last course of purine analog.
  • Accrual Ceiling: 72 evaluable participants
02

Conditions studied

  • Hairy Cell Leukemia

Keywords

  • Monoclonal Antibody
  • Purine Analog
  • Soluble CD25
  • Minimal Residual Disease MRD
  • CD20
03

In context

Leukemia, Hairy Cell

110 studies on the registry are indexed under Leukemia, Hairy Cell; 18 are open to participants now.

This study's enrollment of 69 is above the median of 37 across 88 interventional studies indexed under Leukemia, Hairy Cell.

Browse Leukemia, Hairy Cell studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Evidence of Hairy Cell Leukemia (HCL) by flow cytometry of blood or a solid (lymph node) mass, confirmed by the Laboratory of Pathology, National Cancer Institute (NCI), including positivity for cluster of Differentiation 19 (CD19), cluster of differentiation-22 (CD22), cluster of differentiate 20 (CD20), and Integrin, alpha X (CD11c). Patients with flow cytometry consistent with hairy cell leukemia-variant (HCLv) are eligible, including those with cluster of Differentiation 25 (CD25) and/or cluster of differentiation 103 (CD103) negative disease.
  • bone marrow biopsy (BMBx) or bone marrow aspiration (BMA) consistent with HCL, confirmed by National Institutes of Health (NIH) Laboratory of Pathology, NCI, or the Department of Laboratory Medicine, Clinical Center, NIH, unless the diagnosis can be confirmed from a solid (lymph node) mass.

  • 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 cladribine 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.
    • Increasing lytic bone lesions

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.

  • One of the following:

    • At least 2 prior courses of purine analog
    • 1 prior course of purine analog plus greater than or equal to1 course of rituximab if the response to the course of purine analog lasted less than 1 year.
    • Diagnosis of HCL variant (HCLv)
    • Unmutated (>98% homology to germline) immunoglobulin heavy variable 4-34 (IGHV4-34+) expressing hairy cell leukemia (HCL)/HCLv
  • Eastern Cooperative Oncology Group (ECOG) performance status (102) of 0-3
  • Patients must be able to understand and give informed consent.
  • Creatinine less than or equal to 1.5 or creatinine clearance greater than or equal to 60 ml/min.
  • Bilirubin less than or equal to 2 unless consistent with Gilbert's (total/direct greater than 5), alanine transaminase (ALT) and aspartate aminotransferase (AST) less than or equal to 3 x 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, unless progressive disease more than 2 months after cladribine is documented.
  • 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.
  • 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.

Exclusion criteria

EXCLUSION CRITERIA:

  • Presence of active untreated infection
  • Uncontrolled coronary disease or New York Heart Association (NYHA) class III-IV heart disease.
  • Known infection with human immunodeficiency virus (HIV), hepatitis B or C.
  • 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.
  • Inability to comply with study and/or follow-up procedures.
  • Presence of central nervous system (CNS) disease
  • Patients with history of non-response to both pentostatin plus rituximab and to bendamustine plus rituximab.
  • 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. 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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
69 participants (actual)

Study arms

  • Experimental
    Arm 1 - Non-Randomized to 70 mg/m^2 Bendamustine-Rituximab

    Rituximab + Bendamustine at 70 mg/m\^2 for initial tolerability study (closed)

    Drug: Rituximab · Drug: Bendamustine · Drug: Acetaminophen · Drug: Diphenhydramine · Drug: Epinephrine · Drug: Antihistamines · Drug: Corticosteroids · Drug: Bronchodilators · Other: Intravenous (IV) Saline

  • Experimental
    Arm 2 - Non-randomized to 90 mg/m^2 Bendamustine-Rituximab

    Rituximab + Bendamustine at 90 mg/m\^2 for initial tolerability study (closed)

    Drug: Rituximab · Drug: Bendamustine · Drug: Acetaminophen · Drug: Diphenhydramine · Drug: Epinephrine · Drug: Antihistamines · Drug: Corticosteroids · Drug: Bronchodilators · Other: Intravenous (IV) Saline

  • Active comparator
    Arm 3 - Randomized to 90 mg/m^2 Bendamustine-Rituximab

    Rituximab + Bendamustine (at the tolerated dose)

    Drug: Rituximab · Drug: Bendamustine · Drug: Acetaminophen · Drug: Diphenhydramine · Drug: Epinephrine · Drug: Antihistamines · Drug: Corticosteroids · Drug: Bronchodilators · Other: Intravenous (IV) Saline

  • Active comparator
    Arm 4 - Randomized to Pentostatin-Rituximab

    Rituximab + Pentostatin

    Drug: Pentostatin · Drug: Rituximab · Drug: Acetaminophen · Drug: Diphenhydramine · Drug: Epinephrine · Drug: Antihistamines · Drug: Corticosteroids · Drug: Bronchodilators · Other: Intravenous (IV) Saline

  • Experimental
    Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 with Rituximab

    After initial tolerability studies are completed. Non-randomize up to 4 total participants to Bendamustine and/or Pentostatin with Rituximab

    Drug: Pentostatin · Drug: Rituximab · Drug: Bendamustine · Drug: Acetaminophen · Drug: Diphenhydramine · Drug: Epinephrine · Drug: Antihistamines · Drug: Corticosteroids · Drug: Bronchodilators · Other: Intravenous (IV) Saline

Interventions

  • DrugPentostatin

    28 participants to pentostatin 4 mg/m\^2 days 1 and 15 of each cycle.

    Also known as: Nipent

  • DrugRituximab

    Rituximab 375 mg/m\^2 on day 1, 15 for 6 x 28-day cycles

    Also known as: Rituxan

  • DrugBendamustine

    1-4 participants to bendamustine 90 mg/m\^2/day, days 1 and 2 each cycle

    Also known as: Bendeka, Treanda

  • DrugAcetaminophen

    Treatment of infusion-related symptoms with acetaminophen is recommended.

    Also known as: Tylenol

  • DrugDiphenhydramine

    Treatment of infusion-related symptoms with diphenhydramine is recommended.

    Also known as: Benadryl

  • DrugEpinephrine

    Epinephrine should be available for immediate use in the event of a hypersensitivity reaction to Rituximab.

    Also known as: Adrenaline

  • DrugAntihistamines

    Antihistamines should be available for immediate use in the event of a hypersensitivity reaction to Rituximab.

  • DrugCorticosteroids

    Corticosteroids should be available for immediate use in the event of a hypersensitivity reaction to Rituximab.

    Also known as: Corticoid

  • DrugBronchodilators

    Additional treatment with bronchodilators may be indicated.

    Also known as: Broncholytic

  • OtherIntravenous (IV) Saline

    Additional treatment with intravenous (IV) saline may be indicated.

06

What researchers measure

Primary outcomes

  1. Number of Participants Receiving Pentostatin + Rituximab and Bendamustine + Rituximab Who Achieve a Complete Remission (CR) + Partial Response (PR)

    Number of participants receiving pentostatin + rituximab and bendamustine + rituximab who achieve a CR +PR measured by the following response criteria. Complete remission is all of the following for at least 4 weeks: absolute neutrophil count ≥ 1500/mm\^3, platelets ≥ 100,000/mm\^3, hemoglobin ≥ 11g/dl, spleen non-palpable below the costal margin, or not below costal margin on computed tomography, and circulating hairy cell leukemia (HCL) cells either non-visible on Wright stain or \< 1% by flow cytometry. Partial response is all of the following for at least 4 weeks: neutrophils ≥ 1,500/µL or 50% improvement over baseline, platelets ≥100,000/µL or 50% improvement over baseline, hemoglobin ≥ 11.0 g/dL or 50% improvement over baseline, ≥ 50% decrease in circulating malignant HCL count from the pretreatment baseline, ≥ 50% reduction in sum of products of perpendicular diameters or decrease to ≤ 2 cm in evaluable (\> 2cm) lymphadenopathy.

    Time frame: At end of treatment, approximately 6 months

Secondary outcomes

  1. Pentostatin + Rituximab and Bendamustine + Rituximab in Crossover When Used After Failure of the 1st Regimen

    Compare the 2 regimens - pentostatin + rituximab and bendamustine + rituximab in crossover when used after failure of the 1st regimen.

    Time frame: 4 years

  2. Response Rate

    Response rate between participants who received rituximab plus either pentostatin or bendamustine measured by the following response criteria. Complete remission is all of the following for at least 4 weeks: absolute neutrophil count ≥ 1500/mm\^3, platelets ≥ 100,000/mm\^3, hemoglobin ≥ 11g/dl, spleen non-palpable below the costal margin, or not below costal margin on computed tomography, and circulating hairy cell leukemia (HCL) cells either non-visible on Wright stain or \< 1% by flow cytometry. Partial response is all of the following for at least 4 weeks: neutrophils ≥ 1,500/µL or 50% improvement over baseline, platelets ≥100,000/µL or 50% improvement over baseline, hemoglobin ≥ 11.0 g/dL or 50% improvement over baseline, ≥ 50% decrease in circulating malignant HCL count from the pretreatment baseline, ≥ 50% reduction in sum of products of perpendicular diameters. Progressive disease is appearance of new evaluable lymph nodes \>2cm. Stable disease is none of the above

    Time frame: 4 years

  3. Mechanism of Thrombocytopenia

    The mechanism of thrombocytopenia after purine analog plus rituximab.

    Time frame: 4 years

  4. Hairy Cell Leukemia (HCL) Biology

    HCL biology was determined by cloning, sequencing and characterizing monoclonal immunoglobulin rearrangements, and other genes.

    Time frame: 4 years

  5. Correlation of Measurable Residual Disease (MRD) Levels and Tumor Markers With Response

    Determine if MRD levels and tumor markers (soluble cluster of Differentiation 25 (CD25) and cluster of differentiation-22 (CD22), and real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) correlate with response and clinical endpoints, and if bone marrow magnetic resonance imaging (MRI) signal correlates with bone marrow biopsy (BMBx) results, and whether these tests could in some cases possibly replace BMBx.

    Time frame: 4 years

  6. Measurable Residual Disease (MRD)-Free Survival

    MRD-free survival is defined by the Response criteria.

    Time frame: 4 years

  7. Disease-free Survival (DFS)

    Disease-free survival is the time from start of treatment to documented evidence of disease progression measured by the following response criteria. Progressive disease ≥50% increase in sum of products of perpendicular diameters of evaluable (\> 2cm) lymphadenopathy or appearance of new evaluable lymph nodes \>2cm.

    Time frame: time from start of treatment to documented evidence of disease progression

  8. Overall Survival

    OS is the time between the first day of treatment to the day of death.

    Time frame: time between the first day of treatment to the day of death

  9. Grade 3 and/or 4 Toxicity

    Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Time frame: 4 years

  10. Cluster of Differentiation 4 (CD4+) T-cells

    Cluster of differentiation 4 (CD4+) T-cells assessed by analysis.

    Time frame: 4 years

Other outcomes

  1. Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

    Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Time frame: Date treatment consent signed to date off study, approximately 103 months and 19 days; 133 months and 11 days; 111 months and 15 days; 102 months and 25 days; 44 months and 14 days; and 19 months and 2 days for each group respectively.

07

Results

Posted May 1, 2024

Participant flow

Participant flow — Overall Study
MilestoneNon-Randomized to 70 mg/m2 Bendamustine-RituximabNon-randomized to 90 mg/m^2 Bendamustine-RituximabRandomized to 90 mg/m^2 Bendamustine-RituximabRandomized to Pentostatin-RituximabNon-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab
Started6628281
Completed6624271
Not completed00410
Withdrew: Did not receive 6 cycles.00410

Outcome measures

PrimaryNumber of Participants Receiving Pentostatin + Rituximab and Bendamustine + Rituximab Who Achieve a Complete Remission (CR) + Partial Response (PR)

Number of participants receiving pentostatin + rituximab and bendamustine + rituximab who achieve a CR +PR measured by the following response criteria. Complete remission is all of the following for at least 4 weeks: absolute neutrophil count ≥ 1500/mm\^3, platelets ≥ 100,000/mm\^3, hemoglobin ≥ 11g/dl, spleen non-palpable below the costal margin, or not below costal margin on computed tomography, and circulating hairy cell leukemia (HCL) cells either non-visible on Wright stain or \< 1% by flow cytometry. Partial response is all of the following for at least 4 weeks: neutrophils ≥ 1,500/µL or 50% improvement over baseline, platelets ≥100,000/µL or 50% improvement over baseline, hemoglobin ≥ 11.0 g/dL or 50% improvement over baseline, ≥ 50% decrease in circulating malignant HCL count from the pretreatment baseline, ≥ 50% reduction in sum of products of perpendicular diameters or decrease to ≤ 2 cm in evaluable (\> 2cm) lymphadenopathy.

Time frame:
At end of treatment, approximately 6 months
Reported as:
Count of participants · Participants
Number of Participants Receiving Pentostatin + Rituximab and Bendamustine + Rituximab Who Achieve a Complete Remission (CR) + Partial Response (PR)
ParticipantsNon-Randomized to 70 mg/m2 Bendamustine-RituximabNon-randomized to 90 mg/m^2 Bendamustine-RituximabRandomized to 90 mg/m^2 Bendamustine-RituximabRandomized to Pentostatin-RituximabNon-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab
Complete Remission3420221
Partial Response32440
SecondaryPentostatin + Rituximab and Bendamustine + Rituximab in Crossover When Used After Failure of the 1st Regimen

Compare the 2 regimens - pentostatin + rituximab and bendamustine + rituximab in crossover when used after failure of the 1st regimen.

Time frame:
4 years

Results for this outcome have not been posted.

SecondaryResponse Rate

Response rate between participants who received rituximab plus either pentostatin or bendamustine measured by the following response criteria. Complete remission is all of the following for at least 4 weeks: absolute neutrophil count ≥ 1500/mm\^3, platelets ≥ 100,000/mm\^3, hemoglobin ≥ 11g/dl, spleen non-palpable below the costal margin, or not below costal margin on computed tomography, and circulating hairy cell leukemia (HCL) cells either non-visible on Wright stain or \< 1% by flow cytometry. Partial response is all of the following for at least 4 weeks: neutrophils ≥ 1,500/µL or 50% improvement over baseline, platelets ≥100,000/µL or 50% improvement over baseline, hemoglobin ≥ 11.0 g/dL or 50% improvement over baseline, ≥ 50% decrease in circulating malignant HCL count from the pretreatment baseline, ≥ 50% reduction in sum of products of perpendicular diameters. Progressive disease is appearance of new evaluable lymph nodes \>2cm. Stable disease is none of the above

Time frame:
4 years

Results for this outcome have not been posted.

SecondaryMechanism of Thrombocytopenia

The mechanism of thrombocytopenia after purine analog plus rituximab.

Time frame:
4 years

Results for this outcome have not been posted.

SecondaryHairy Cell Leukemia (HCL) Biology

HCL biology was determined by cloning, sequencing and characterizing monoclonal immunoglobulin rearrangements, and other genes.

Time frame:
4 years

Results for this outcome have not been posted.

SecondaryCorrelation of Measurable Residual Disease (MRD) Levels and Tumor Markers With Response

Determine if MRD levels and tumor markers (soluble cluster of Differentiation 25 (CD25) and cluster of differentiation-22 (CD22), and real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) correlate with response and clinical endpoints, and if bone marrow magnetic resonance imaging (MRI) signal correlates with bone marrow biopsy (BMBx) results, and whether these tests could in some cases possibly replace BMBx.

Time frame:
4 years

Results for this outcome have not been posted.

SecondaryMeasurable Residual Disease (MRD)-Free Survival

MRD-free survival is defined by the Response criteria.

Time frame:
4 years

Results for this outcome have not been posted.

SecondaryDisease-free Survival (DFS)

Disease-free survival is the time from start of treatment to documented evidence of disease progression measured by the following response criteria. Progressive disease ≥50% increase in sum of products of perpendicular diameters of evaluable (\> 2cm) lymphadenopathy or appearance of new evaluable lymph nodes \>2cm.

Time frame:
time from start of treatment to documented evidence of disease progression

Results for this outcome have not been posted.

SecondaryOverall Survival

OS is the time between the first day of treatment to the day of death.

Time frame:
time between the first day of treatment to the day of death

Results for this outcome have not been posted.

SecondaryGrade 3 and/or 4 Toxicity

Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Time frame:
4 years

Results for this outcome have not been posted.

SecondaryCluster of Differentiation 4 (CD4+) T-cells

Cluster of differentiation 4 (CD4+) T-cells assessed by analysis.

Time frame:
4 years

Results for this outcome have not been posted.

Other pre-specifiedNumber of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Time frame:
Date treatment consent signed to date off study, approximately 103 months and 19 days; 133 months and 11 days; 111 months and 15 days; 102 months and 25 days; 44 months and 14 days; and 19 months and 2 days for each group respectively.
Reported as:
Count of participants · Participants
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
ParticipantsNon-Randomized to 70 mg/m2 Bendamustine-RituximabNon-randomized to 90 mg/m^2 Bendamustine-RituximabRandomized to 90 mg/m^2 Bendamustine-RituximabRandomized to Pentostatin-RituximabNon-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)6628281

Adverse events

Collected over Date treatment consent signed to date off study, approximately 103 months and 19 days; 133 months and 11 days; 111 months and 15 days; 102 months and 25 days; 44 months and 14 days; and 19 months and 2 days for each group respectively.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Non-Randomized to 70 mg/m2 Bendamustine-Rituximab0/6 (0%)0/6 (0%)6/6 (100%)
Non-randomized to 90 mg/m^2 Bendamustine-Rituximab0/6 (0%)0/6 (0%)6/6 (100%)
Randomized to 90 mg/m^2 Bendamustine-Rituximab3/28 (10.7%)8/28 (28.6%)28/28 (100%)
Randomized to Pentostatin-Rituximab5/28 (17.9%)7/28 (25%)28/28 (100%)
Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab0/1 (0%)0/1 (0%)1/1 (100%)
Most frequent serious events
Showing 10 of 21
Most frequent serious events
EventNon-Randomized to 70 mg/m2 Bendamustine-RituximabNon-randomized to 90 mg/m^2 Bendamustine-RituximabRandomized to 90 mg/m^2 Bendamustine-RituximabRandomized to Pentostatin-RituximabNon-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab
Febrile neutropeniaBlood and lymphatic system disorders0/60/63/282/280/1
Allergic reactionImmune system disorders0/60/60/282/280/1
DyspneaRespiratory, thoracic and mediastinal disorders0/60/60/282/280/1
Lung infectionInfections and infestations0/60/62/282/280/1
SyncopeNervous system disorders0/60/62/280/280/1
Upper respiratory infectionInfections and infestations0/60/61/282/280/1
Acute kidney injuryRenal and urinary disorders0/60/61/281/280/1
ChillsGeneral disorders0/60/61/280/280/1
DehydrationMetabolism and nutrition disorders0/60/61/280/280/1
DiarrheaGastrointestinal disorders0/60/61/280/280/1
Most frequent other events
Showing 10 of 166
Most frequent other events
EventNon-Randomized to 70 mg/m2 Bendamustine-RituximabNon-randomized to 90 mg/m^2 Bendamustine-RituximabRandomized to 90 mg/m^2 Bendamustine-RituximabRandomized to Pentostatin-RituximabNon-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab
Alkaline phosphatase increasedInvestigations3/62/68/285/281/1
AnorexiaMetabolism and nutrition disorders1/61/67/284/281/1
Atrial fibrillationCardiac disorders0/60/60/282/281/1
Blurred visionEye disorders1/60/62/282/281/1
CataractEye disorders0/60/60/280/281/1
ConstipationGastrointestinal disorders3/61/68/289/281/1
DehydrationMetabolism and nutrition disorders0/60/60/281/281/1
GlaucomaEye disorders0/60/60/280/281/1
ParesthesiaNervous system disorders1/61/63/284/281/1
Eye disorders - Other, Macular degenerationEye disorders0/60/60/280/281/1

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Non-Randomized to 70 mg/m2 Bendamustine-RituximabNon-randomized to 90 mg/m^2 Bendamustine-RituximabRandomized to 90 mg/m^2 Bendamustine-RituximabRandomized to Pentostatin-RituximabNon-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With RituximabTotal
<=18 years000000
Between 18 and 65 years261615039
>=65 years401213130
Age, Continuous
Age, Continuous(years)Non-Randomized to 70 mg/m2 Bendamustine-RituximabNon-randomized to 90 mg/m^2 Bendamustine-RituximabRandomized to 90 mg/m^2 Bendamustine-RituximabRandomized to Pentostatin-RituximabNon-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With RituximabTotal
Mean66.65 ± 3.0358.67 ± 3.1461.87 ± 9.7561.55 ± 12.2371.2 ± 062.01 ± 10.14
Sex: Female, Male
Sex: Female, Male(Participants)Non-Randomized to 70 mg/m2 Bendamustine-RituximabNon-randomized to 90 mg/m^2 Bendamustine-RituximabRandomized to 90 mg/m^2 Bendamustine-RituximabRandomized to Pentostatin-RituximabNon-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With RituximabTotal
Female2064012
Male462224157
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Non-Randomized to 70 mg/m2 Bendamustine-RituximabNon-randomized to 90 mg/m^2 Bendamustine-RituximabRandomized to 90 mg/m^2 Bendamustine-RituximabRandomized to Pentostatin-RituximabNon-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With RituximabTotal
Hispanic or Latino000000
Not Hispanic or Latino662826167
Unknown or Not Reported000202
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Non-Randomized to 70 mg/m2 Bendamustine-RituximabNon-randomized to 90 mg/m^2 Bendamustine-RituximabRandomized to 90 mg/m^2 Bendamustine-RituximabRandomized to Pentostatin-RituximabNon-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With RituximabTotal
American Indian or Alaska Native000000
Asian010001
Native Hawaiian or Other Pacific Islander000000
Black or African American002103
White652627165
More than one race000000
Unknown or Not Reported000000
Region of Enrollment
Region of Enrollment(participants)Non-Randomized to 70 mg/m2 Bendamustine-RituximabNon-randomized to 90 mg/m^2 Bendamustine-RituximabRandomized to 90 mg/m^2 Bendamustine-RituximabRandomized to Pentostatin-RituximabNon-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With RituximabTotal
United States662828169
08

Study locations

1 site
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
09

References and documents

Publications

  • Bouroncle BA. Thirty-five years in the progress of hairy cell leukemia. Leuk Lymphoma. 1994;14 Suppl 1:1-12. PubMed 7820038 ↗
  • Kreitman 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 11399570 ↗
  • Jemal 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 17237035 ↗
  • Schroeder B, Yuan C, Wang HW, Mohindroo C, Zhou H, Raffeld M, Xi L, Arons E, Feurtado J, James-Echenique L, Calvo KR, Maric I, Kreitman RJ. Phase 2 trial of rituximab with either pentostatin or bendamustine for multiply relapsed or refractory hairy cell leukemia. Blood. 2026 Feb 12;147(7):725-738. doi: 10.1182/blood.2025031243. PubMed 41060318 ↗

Study documents

  • Protocol and statistical analysis plan · Sep 6, 2022
  • Informed consent form · Oct 11, 2022
  • Informed consent form · Oct 11, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

Supporting information: Study protocol, Sap, Icf

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 22, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01059786
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Robert Kreitman, M.D. (Principal Investigator, National Cancer Institute (NCI)) — Principal investigator
First posted
Feb 1, 2010
Start date
Jul 1, 2010
Primary completion
Dec 15, 2022
Completion
Jun 30, 2031 (estimated)
Results posted
May 1, 2024
Last update
Jul 22, 2026

Study contacts

Robert J Kreitman, M.D.
principal investigator · National Cancer Institute (NCI)

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.

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Discussion

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