Cyclophosphamide and Rituximab Followed By Vaccine Therapy in Treating Patients With Chronic Lymphocytic Leukemia

May 1, 2012 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phase II Randomized Trial of Early Versus Late Vaccination in Patients With High Risk CLL

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, 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 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. Vaccines may help the body build an effective immune response to kill cancer cells. Giving cyclophosphamide and rituximab together with vaccine therapy may kill more cancer cells.

PURPOSE: This randomized phase II trial is studying cyclophosphamide and rituximab followed by two different schedules of vaccine therapy to compare how well they work in treating patients with chronic lymphocytic leukemia.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the efficacy and toxicity of cyclophosphamide and rituximab in patients with previously untreated, high-risk chronic lymphocytic leukemia.
  • Determine, preliminarily, the efficacy and toxicity of early vs delayed administration of vaccine therapy comprising KGEL and autologous tumor cells after cyclophosphamide and rituximab in these patients.
  • Compare the magnitude of the T-cell response to early vs delayed administration of this vaccine after rituximab and cyclophosphamide and correlate these responses with the extent of immune reconstruction.

OUTLINE: This is a randomized phase II study for patients with asymptomatic or minimally symptomatic, untreated CLL with poor-risk features.

Patients undergo peripheral blood collection for vaccine production. Patients then receive rituximab IV over at least 4 hours on days 1 and 2 in course 1 and on day 1 only in subsequent courses and cyclophosphamide IV over 1 hour on day 1. Treatment with rituximab and cyclophosphamide repeats every 21 days for up to 6 cycles in the absence of disease progression. Patients undergo evaluation 4 weeks after completion of rituximab and cyclophosphamide. Patients achieving partial or complete response are randomized to 1 of 2 vaccine treatment arms.

  • Arm I (early administration): Beginning 2 weeks after evaluation, patients receive vaccine therapy comprising an autologous tumor admixed with an allogeneic vaccine (KGEL) that produces sargramostim (GM-CSF) and autologous tumor cells intradermally. Treatment repeats every 3 weeks for 6 courses in the absence of unacceptable toxicity.
  • Arm II (late administration): Beginning 20 weeks after evaluation, patients receive vaccine therapy comprising KGEL and autologous tumor cells intradermally. Treatment repeats every 3 weeks for 6 courses in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months until disease progression.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Study Type

Interventional

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
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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:

  • Diagnosis of chronic lymphocytic leukemia (CLL)

  • Meets 1 of the following high-risk features:

    • 17p deletion by fluorescent in situ hybridization (FISH)
    • 11q deletion by FISH
    • Unmutated immunoglobulin heavy chain variable region (IgVH) genes, defined as ≥ 98% homology with germline in a Clinical Laboratory Improvement Act (CLIA) approved laboratory
  • Any stage disease

  • Previously untreated disease

    • Not requiring immediate treatment
  • Absolute lymphocyte count ≥ 20,000/mm³

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Creatinine ≤ 2.0 mg/dL
  • Bilirubin ≤ 2 mg/dL (unless secondary to obstructive cholestasis from lymphadenopathy or Gilbert's disease)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active infections requiring oral or intravenous antibiotics
  • No autoimmune disorder (e.g., autoimmune hemolytic anemia) requiring corticosteroids before the start of study vaccination
  • No other malignancy except nonbasal cell skin cancer, carcinoma in situ of the cervix, or tumor that was treated with curative intent ≥ 2 years ago

PRIOR CONCURRENT THERAPY:

  • No prior therapy for CLL

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: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Efficacy and toxicity
T-cell response to early versus late vaccine therapy comprising KGEL and autologous tumor cells

Collaborators and Investigators

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

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Yvette L. Kasamon, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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

August 1, 2006

Primary Completion (Actual)

May 1, 2007

Study Completion (Actual)

May 1, 2007

Study Registration Dates

First Submitted

June 22, 2006

First Submitted That Met QC Criteria

June 22, 2006

First Posted (Estimate)

June 23, 2006

Study Record Updates

Last Update Posted (Estimate)

May 3, 2012

Last Update Submitted That Met QC Criteria

May 1, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • J0579 CDR0000481362
  • P30CA006973 (U.S. NIH Grant/Contract)
  • JHOC-J0579
  • JHOC-NA_00000982

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.

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