Trial record 4 of 20 for:    Recruiting, Not yet recruiting, Available Studies | "Leukemia, Hairy Cell"

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01059786
Recruitment Status : Recruiting
First Posted : February 1, 2010
Last Update Posted : March 20, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:


  • 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.


  • 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.


- 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.


  • 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.

Condition or disease Intervention/treatment Phase
Hairy Cell Leukemia Drug: Pentostatin Drug: Rituximab Drug: Bendamustine Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia
Study Start Date : December 18, 2009
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : December 31, 2018

Arm Intervention/treatment
Experimental: Arm 1
Rituximab + Bendamustine
Drug: Rituximab
Rituximab 375 mg/m2 on day 1, 15 for 6 x 28-day cycles (all 68 patients)
Drug: Bendamustine
28 patients to bendamustine 90 mg/m2/day, days 1 and 2 each cycle
Experimental: Arm 2
Rituximab + Pentostatin
Drug: Pentostatin
28 patients to pentostatin 4 mg/m2 days 1 and 15 of each cycle.
Drug: Rituximab
Rituximab 375 mg/m2 on day 1, 15 for 6 x 28-day cycles (all 68 patients)

Primary Outcome Measures :
  1. 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. [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Compare rituximab plus either pentostatin or bendamustine in termsof MRD-free survival, disease-free survival, overall survival and toxicity, including to CD4+ T-cells. [ Time Frame: 4 years ]
  2. Compare the 2 regimens in crossover when used after failure of the1st regimen. [ Time Frame: 4 years ]
  3. Determine if MRD levels and tumor markers (soluble CD25 and CD22,and RQ-PCR) correlate with response and clinical endpoints, and if bone marrow MRI signal correlates with BMBx results, and whetherthese tests could in some cases possibly re... [ Time Frame: 4 years ]
  4. Study the mechanism of thrombocytopenia after purine analog plusrituximab. [ Time Frame: 4 years ]
  5. Study HCL biology by cloning, sequencing and characterizing monoclonal immunoglobulin rearrangements, and other genes. [ Time Frame: 4 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • INCLUSION CRITERIA: Evidence of HCL by flow cytometry of blood or a solid (lymph node) mass, confirmed by the Laboratory of Pathology, NCI, including positivity for CD19, CD22, CD20, and CD11c. Patients with flow cytometry consistent with HCL variant (HCLv) are eligible, including those with CD25 and/or CD103 negative disease. or BMA consistent with HCL, confirmed by 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 (ANC less than 1000 cells/microl).

Anemia (Hgb less than 10g/dL).

Thrombocytopenia (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 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. 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) IGHV4-34+expressing HCL/HCLv ECOG performance status (100) 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/ml. Bilirubin less than or equal to 2 unless consistent with Gilbert s (total/direct greater than 5), ALT and 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.

EXCLUSION CRITERIA: Presence of active untreated infection Uncontrolled coronary disease or NYHA class III-IV heart disease. Known infection with 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 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 patient s 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01059786

Contact: Theresa Yu, R.N. (301) 480-6195
Contact: Robert J Kreitman, M.D. (301) 480-6187

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Robert J Kreitman, M.D. National Cancer Institute (NCI)

Additional Information:
Responsible Party: National Cancer Institute (NCI) Identifier: NCT01059786     History of Changes
Other Study ID Numbers: 100025
First Posted: February 1, 2010    Key Record Dates
Last Update Posted: March 20, 2018
Last Verified: December 14, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Monoclonal Antibody
Purine Analog
Soluble CD25
Minimal Residual Disease MRD
Hairy Cell Leukemia

Additional relevant MeSH terms:
Leukemia, Hairy Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Adenosine Deaminase Inhibitors
Enzyme Inhibitors