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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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
  

  Detailed Summary:

  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 10 complete + 10 partial remissions (CR+PR= 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 CD25 (LMB-2) and CD22 (BL22 and 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 CLL, and is effective with rituximab for relapsed/refractory CLL. Its use in HCL is unreported.
  • CRs with minimal residual disease (MRD) by immunohistochemistry of bone marrow biopsy (BMBx IHC), can relapse early. Tests for HCL MRD in blood or marrow include flow cytometry (FACS) or PCR using consensus primers. The most sensitive MRD test in HCL is real-time quantitative PCR using sequence-specific primers (RQ-PCR).
  • Sponsor: National Cancer Institute (NCI)
    

    Current Primary Outcome: 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 ]
    
    

    Original Primary Outcome: 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: 5-6 months after beginning the protocol ]
    
    

    Current Secondary Outcome:

    • 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 ]
    • Compare the 2 regimens in crossover when used after failure of the1st regimen. [ Time Frame: 4 years ]
    • 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 ]
    • Study the mechanism of thrombocytopenia after purine analog plusrituximab. [ Time Frame: 4 years ]
    • Study HCL biology by cloning, sequencing and characterizing monoclonal immunoglobulin rearrangements, and other genes. [ Time Frame: 4 years ]
    
    
    

    Original Secondary Outcome: To compare rituximab plus either pentostatin or bendamustine in terms of MRD-free survival and disease-free survival, and toxicity, including to CD4+ T-cells. To determine if MRD levels and tumor markers correlate with response
    
    Information By: National Institutes of Health Clinical Center (CC)
    

    Dates:
    Date Received: January 29, 2010
    Date Started: December 15, 2009
    Date Completion: December 31, 2018
    Last Updated: May 13, 2017
    Last Verified: March 21, 2017