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

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ClinicalTrials.gov Identifier: NCT00343447
Recruitment Status : Withdrawn
First Posted : June 23, 2006
Last Update Posted : May 3, 2012
Information provided by (Responsible Party):

Study Description
Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Leukemia Biological: autologous tumor cell vaccine Biological: rituximab Drug: cyclophosphamide Phase 2

Detailed Description:


  • 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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Randomized Trial of Early Versus Late Vaccination in Patients With High Risk CLL
Study Start Date : August 2006
Primary Completion Date : May 2007
Study Completion Date : May 2007

Arms and Interventions

Outcome Measures

Primary Outcome Measures :
  1. Efficacy and toxicity
  2. T-cell response to early versus late vaccine therapy comprising KGEL and autologous tumor cells

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • No prior therapy for CLL
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00343447

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Study Chair: Yvette L. Kasamon, MD Sidney Kimmel Comprehensive Cancer Center
More Information

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00343447     History of Changes
Other Study ID Numbers: J0579 CDR0000481362
P30CA006973 ( U.S. NIH Grant/Contract )
First Posted: June 23, 2006    Key Record Dates
Last Update Posted: May 3, 2012
Last Verified: May 2012

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists