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

This study has suspended participant recruitment.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01059786
First received: January 29, 2010
Last updated: November 20, 2014
Last verified: April 2014
  Purpose

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.

Condition Intervention Phase
Hairy Cell Leukemia
Drug: Pentostatin
Drug: Rituximab
Drug: Bendamustine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • compare the 2 regimens in crossover when used after failure of the1st regimen. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • study the mechanism of thrombocytopenia after purine analog plusrituximab. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • study HCL biology by cloning, sequencing and characterizing monoclonal immunoglobulin rearrangements, and other genes. [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: December 2009
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Rituximab + Bendamustine
Drug: Rituximab
N/A
Drug: Bendamustine
N/A
Experimental: Arm 2
Rituximab + Pentostatin
Drug: Pentostatin
N/A
Drug: Rituximab
N/A

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

2.1.1.1. Evidence of HCL by flow cytometry of blood, 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.

2.1.1.2.BMBx consistent with HCL, confirmed by NIH Laboratory of Pathology, NCI, or the Department of Laboratory Medicine, Clinical Center, NIH.

2.1.1.3. 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.

2.1.1.4. 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.

2.1.1.5. ECOG performance status (100) of 0-3

2.1.1.6. Patients must be able to understand and give informed consent.

2.1.1.7. Creatinine less than or equal to 1.5 or creatinine clearance greater than or equal to 60 ml/ml.

2.1.1.8. 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.

2.1.1.9. No other therapy (i.e. chemotherapy, interferon) for 4 weeks prior to study entry, or cladribine for 6 months prior to study entry.

2.1.1.10. Age at least 18

2.1.1.11. 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:

2.1.2.1. Presence of active untreated infection

2.1.2.2. Uncontrolled coronary disease or NYHA class III-IV heart disease.

2.1.2.3. Known infection with HIV, hepatitis B or C.

2.1.2.4. Pregnant or lactating women.

2.1.2.5. 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.

2.1.2.6. Inability to comply with study and/or follow-up procedures.

2.1.2.7. Presence of CNS disease

2.1.2.8. Patients with history of non-response to both pentostatin plus rituximab and to bendamustine plus rituximab.

2.1.2.9. 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.

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01059786

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Robert J Kreitman, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01059786     History of Changes
Other Study ID Numbers: 100025, 10-C-0025
Study First Received: January 29, 2010
Last Updated: November 20, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Monoclonal Antibody
Purine Analog
Soluble CD25
Minimal Residual Disease MRD
CD20
Hairy Cell Leukemia

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

ClinicalTrials.gov processed this record on November 24, 2014