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

NCT01059786 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: 10002510-C-0025
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hairy Cell Leukemia

Keywords

Monoclonal Antibody; Purine Analog; Soluble CD25; Minimal Residual Disease MRD; CD20

Outcome Measures

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.

  At end of treatment, approximately 6 months

Secondary Outcomes (10)

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

  4 years

• Response Rate

  4 years

• Mechanism of Thrombocytopenia

  4 years

• Hairy Cell Leukemia (HCL) Biology

  4 years

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

  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)

  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.

Study Arms (5)

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

ACTIVE COMPARATOR

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

Arm 4 - Randomized to Pentostatin-Rituximab

ACTIVE COMPARATOR

Rituximab + Pentostatin

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

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

EXPERIMENTAL

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

Pentostatin DRUG

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

Also known as: Nipent

Arm 4 - Randomized to Pentostatin-Rituximab; Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 with Rituximab

Rituximab DRUG

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

Also known as: Rituxan

Arm 1 - Non-Randomized to 70 mg/m^2 Bendamustine-Rituximab; Arm 2 - Non-randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 3 - Randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 4 - Randomized to Pentostatin-Rituximab; Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 with Rituximab

Bendamustine DRUG

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

Also known as: Bendeka, Treanda

Arm 1 - Non-Randomized to 70 mg/m^2 Bendamustine-Rituximab; Arm 2 - Non-randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 3 - Randomized to 90 mg/m^2 Bendamustine-Rituximab; Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 with Rituximab

Acetaminophen DRUG

Treatment of infusion-related symptoms with acetaminophen is recommended.

Also known as: Tylenol

Arm 1 - Non-Randomized to 70 mg/m^2 Bendamustine-Rituximab; Arm 2 - Non-randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 3 - Randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 4 - Randomized to Pentostatin-Rituximab; Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 with Rituximab

Diphenhydramine DRUG

Treatment of infusion-related symptoms with diphenhydramine is recommended.

Also known as: Benadryl

Arm 1 - Non-Randomized to 70 mg/m^2 Bendamustine-Rituximab; Arm 2 - Non-randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 3 - Randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 4 - Randomized to Pentostatin-Rituximab; Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 with Rituximab

Epinephrine DRUG

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

Also known as: Adrenaline

Arm 1 - Non-Randomized to 70 mg/m^2 Bendamustine-Rituximab; Arm 2 - Non-randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 3 - Randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 4 - Randomized to Pentostatin-Rituximab; Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 with Rituximab

Antihistamines DRUG

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

Arm 1 - Non-Randomized to 70 mg/m^2 Bendamustine-Rituximab; Arm 2 - Non-randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 3 - Randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 4 - Randomized to Pentostatin-Rituximab; Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 with Rituximab

Corticosteroids DRUG

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

Also known as: Corticoid

Arm 1 - Non-Randomized to 70 mg/m^2 Bendamustine-Rituximab; Arm 2 - Non-randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 3 - Randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 4 - Randomized to Pentostatin-Rituximab; Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 with Rituximab

Bronchodilators DRUG

Additional treatment with bronchodilators may be indicated.

Also known as: Broncholytic

Arm 1 - Non-Randomized to 70 mg/m^2 Bendamustine-Rituximab; Arm 2 - Non-randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 3 - Randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 4 - Randomized to Pentostatin-Rituximab; Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 with Rituximab

Intravenous (IV) Saline OTHER

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

Arm 1 - Non-Randomized to 70 mg/m^2 Bendamustine-Rituximab; Arm 2 - Non-randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 3 - Randomized to 90 mg/m^2 Bendamustine-Rituximab; Arm 4 - Randomized to Pentostatin-Rituximab; Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 with Rituximab

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Bouroncle BA. Thirty-five years in the progress of hairy cell leukemia. Leuk Lymphoma. 1994;14 Suppl 1:1-12.

  PMID: 7820038 BACKGROUND

• 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.

  PMID: 11399570 BACKGROUND

• 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.

  PMID: 17237035 BACKGROUND

• Schroeder B, Yuan CM, Wang HW, Mohindroo C, Zhou H, Raffeld M, Xi L, Arons E, Feurtado JC, 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. 2025 Oct 8:blood.2025031243. doi: 10.1182/blood.2025031243. Online ahead of print.

  PMID: 41060318 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia, Hairy Cell; Neoplasm, Residual

Interventions

Pentostatin; Rituximab; Bendamustine Hydrochloride; Acetaminophen; Diphenhydramine; Epinephrine; Histamine Antagonists; Adrenal Cortex Hormones; Bronchodilator Agents; Sodium Chloride

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Ethanolamines; Amino Alcohols; Alcohols; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Autonomic Agents; Peripheral Nervous System Agents; Anti-Asthmatic Agents; Respiratory System Agents; Therapeutic Uses; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Robert J. Kreitman
• Organization: National Cancer Institute

kreitmar@mail.nih.gov

301-480-6187

Study Officials

• Robert J Kreitman, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 29, 2010
• First Posted: February 1, 2010
• Study Start: July 1, 2010
• Primary Completion: December 15, 2022
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 12, 2025
• Results First Posted: May 1, 2024

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)