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Trial record 23 of 202 for:    "Leukemia" | "Sargramostim"

Pentostatin, Alemtuzumab, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

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ClinicalTrials.gov Identifier: NCT00669318
Recruitment Status : Completed
First Posted : April 30, 2008
Results First Posted : June 20, 2014
Last Update Posted : July 1, 2014
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE April 29, 2008
First Posted Date  ICMJE April 30, 2008
Results First Submitted Date  ICMJE May 20, 2014
Results First Posted Date  ICMJE June 20, 2014
Last Update Posted Date July 1, 2014
Study Start Date  ICMJE July 2008
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2014)
Complete Response Rate [ Time Frame: Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total) ]
A Complete Response (CR) requires the disappearance of all nodes, a non-palpable liver and spleen, no constitutional symptoms, absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, and lymphocytes <4000/uL. In addition, a bone marrow biopsy with evidence of <30% lymphocytes and no nodules. Here we report the rate of complete response as the number of patients attaining a CR status divided by the total number of evaluable patients. The 95% CI is estimated using the binomial distribution.
Original Primary Outcome Measures  ICMJE
 (submitted: April 29, 2008)
Proportion of complete responses
Change History Complete list of historical versions of study NCT00669318 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2014)
  • Overall Response Rate (Complete and Partial Response) [ Time Frame: Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total) ]
    A Complete Response (CR) requires the disappearance of all nodes, a non-palpable liver and spleen, no constitutional symptoms, absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, and lymphocytes <4000/uL. A bone marrow biopsy with evidence of <30% lymphocytes and no nodules. Patients who fulfill all criteria for a CR but have a persistent anemia, thrombocytopenia, or neutropenia related to drug toxicity will be classified as CR with incomplete marrow recovery (CRi). A Partial Response (PR) requires a 50% reduction in nodes and liver/spleen measurements and at least two of the following: absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, or a >50% reduction in lymphocytes. Here we report the rate of overall response as the number of patients attaining a CR, PR, or CRi status divided by the total number of evaluable patients. The 95% CI is estimated using the binomial distribution.
  • Overall Survival [ Time Frame: Follow-up status and retreatment information will be collected up to 5 years from registration ]
    Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
  • Progression-free Survival [ Time Frame: Follow-up status and retreatment information will be collected up to 5 years from registration ]
    The progression-free survival (PFS) time is defined as the time from registration to progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
  • Time to Retreatment [ Time Frame: Follow-up status and retreatment information will be collected up to 5 years from registration ]
    Time to subsequent therapy is defined to be the time from the registration to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2008)
  • Overall Response Rate (Complete and Partial Response)
  • Overall Survival
  • Progression-free Survival
  • Duration of response
  • Time to subsequent therapy
  • IgVh gene mutation, CD38, ZAP-70, CD49d, and FISH status of chronic lymphocytic leukemia clones
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pentostatin, Alemtuzumab, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Official Title  ICMJE Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) With Pentostatin, Alemtuzumab, and Low Dose Rituximab: A Phase II Clinical Trial
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as pentostatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as alemtuzumab and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving pentostatin together with alemtuzumab and rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving pentostatin together with alemtuzumab and rituximab works in treating patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

Detailed Description

OBJECTIVES:

Primary

  • To assess the rate of complete and overall response in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma treated with pentostatin, alemtuzumab, and low-dose rituximab.
  • To monitor and assess toxicity of this treatment regimen.

Secondary

  • To determine the overall and progression-free survival, duration of response, and time to next treatment.
  • To assess the correlation between individual prognostic markers (17p-, 11q-, unmutated VH gene, VH3-21, ZAP-70+, CD38+, CD49d, and β2 microglobulin, miRNA profiles, angiogenesis status, and karyotypes of CpG stimulated cells) and clinical outcome.

OUTLINE: This is a multicenter study.

  • Course 1: Patients receive pentostatin IV on days 8 and 22; alemtuzumab subcutaneously (SC) on days 3-5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; and sargramostim (GM-CSF) SC on days 10-14 and 24-28. Patients then proceed to course 2.
  • Courses 2 and 3: Patients receive pentostatin IV on days 1 and 15; alemtuzumab SC and rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; and GM-CSF SC on days 3-7 and 17-21. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).

Treatment continues in the absence of disease progression or unacceptable toxicity.

Blood is collected on days 1, 3, 8, and 10 of course 1 for monoclonal antibody studies. Samples are analyzed for serum concentration of alemtuzumab and rituximab by ELISA and PCR; CH50 assay; complement activation and cytokine levels by ELISA; NK cell activation; and NK cell phenotype by immunofluorescent staining and flow cytometry.

After completion of study treatment, patients are followed up monthly for 6 months, every 3 months for 6 months, and then every 6-12 months for up to 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Lymphoma
Intervention  ICMJE
  • Biological: alemtuzumab
  • Biological: rituximab
  • Drug: pentostatin
  • Drug: sargramostim
    Other Name: GM-CSF
Study Arms  ICMJE Experimental: Treatment (Pentostatin, Alemtuzumab, Rituximab)

Course 1: Patients receive:

  • 2 mg/m^2 pentostatin IV on days 8 and 22;
  • 3 mg alemtuzumab subcutaneously (SC) on day 3;
  • 10 mg alemtuzumab SC on day 4;
  • 30 mg alemtuzumab SC on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33;
  • 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33;
  • 6 mg Sargramostim (GM-CSF) SC on days 10-14. Patients then proceed to course 2.

Courses 2 and 3: Patients receive:

  • 2 mg/m^2 pentostatin IV on days 1 and 15;
  • 30 mg alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26;
  • 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26;
  • 6 mg GM-CSF SC on days 3-7. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).
Interventions:
  • Biological: alemtuzumab
  • Biological: rituximab
  • Drug: pentostatin
  • Drug: sargramostim
Publications * Zent CS, Taylor RP, Lindorfer MA, Beum PV, LaPlant B, Wu W, Call TG, Bowen DA, Conte MJ, Frederick LA, Link BK, Blackwell SE, Veeramani S, Baig NA, Viswanatha DS, Weiner GJ, Witzig TE. Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells. Am J Hematol. 2014 Jul;89(7):757-65. doi: 10.1002/ajh.23737. Epub 2014 Apr 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 20, 2014)
41
Original Enrollment  ICMJE
 (submitted: April 29, 2008)
42
Actual Study Completion Date  ICMJE May 2014
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) meeting the following criteria:

    • Minimum threshold peripheral blood lymphocyte count of 5 x 10^9/L (CLL variant) OR adenopathy > 1 cm or palpable splenomegaly (SLL variant)
    • Immunophenotypic demonstrations of a population of B lymphocytes (as defined by CD19+) that are monoclonal (by light chain exclusion) AND have ≥ 3 of the following characteristics:

      • CD5+
      • CD23+
      • Dim surface light chain expression
      • Dim surface CD20 expression
      • FISH analysis is negative for IGH/CCND1 and/or immunostaining is negative for cyclin D1 expression
  • Must have progressive disease as indicated by any of the following characteristics (based on standard criteria for treatment):

    • Symptomatic CLL characterized by any of the following:

      • Weight loss > 10% within the past 6 months
      • Extreme fatigue
      • Fevers > 38.5° C (not due to infection)
      • Drenching night sweats without evidence of infection
    • Evidence of progressive bone marrow failure with hemoglobin < 11 g/dL or platelet count < 100 x 10^9/L
    • Massive and progressive splenomegaly (> 6 cm below left costal margin)
    • Massive (> 10 cm) or rapidly progressive lymphadenopathy

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-3
  • Creatinine ≤ 2 times upper limit of normal (ULN)
  • Total bilirubin ≤ 3.0 times ULN OR direct bilirubin ≤ 1.5 times ULN
  • AST ≤ 3.0 times ULN (unless due to hemolysis or CLL)
  • Willing to provide mandatory blood samples for research studies
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for up to 12 months after completion of study treatment
  • No other active primary malignancy that requires treatment or limits survival to ≤ 2 years
  • No active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
  • No New York Heart Association class III or IV heart disease
  • No myocardial infarction within the past month
  • No uncontrolled infection
  • No HIV infection or AIDS
  • No active hepatitis B infection (i.e., HBsAg or HBeAg positivity) or hepatitis C infection by serology
  • No other comorbid condition

PRIOR CONCURRENT THERAPY:

  • No more than 3 prior treatment regimens for CLL that included purine analogue drugs (e.g., fludarabine, pentostatin, or cladribine) OR previously untreated CLL in patients with high-risk disease due to 17p13 deletion on FISH analysis
  • More than 4 weeks since prior major surgery
  • More than 2 months since prior alemtuzumab
  • Prior corticosteroids allowed
  • No concurrent continuous systemic corticosteroids
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00669318
Other Study ID Numbers  ICMJE LS0881
LS0881 ( Other Identifier: Mayo Clinic Cancer Center )
08-000673 ( Other Identifier: Mayo Clinic IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Clive S. Zent, MD Mayo Clinic
PRS Account Mayo Clinic
Verification Date June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP