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

June 20, 2014 updated by: Mayo Clinic

Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) With Pentostatin, Alemtuzumab, and Low Dose Rituximab: A Phase II Clinical Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

41

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242-1002
        • Holden Comprehensive Cancer Center at University of Iowa
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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).
Biological: rituximab
Biological: alemtuzumab
Drug: pentostatin
Drug: sargramostim
Other Names:
  • GM-CSF

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total)
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.
Follow-up status and retreatment information will be collected up to 5 years from registration
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.
Follow-up status and retreatment information will be collected up to 5 years from registration
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
Follow-up status and retreatment information will be collected up to 5 years from registration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Clive S. Zent, MD, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2008

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

April 29, 2008

First Submitted That Met QC Criteria

April 29, 2008

First Posted (Estimate)

April 30, 2008

Study Record Updates

Last Update Posted (Estimate)

July 1, 2014

Last Update Submitted That Met QC Criteria

June 20, 2014

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LS0881 (Other Identifier: Mayo Clinic Cancer Center)
  • 08-000673 (Other Identifier: Mayo Clinic IRB)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoma

Clinical Trials on rituximab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Japan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe