Vaccine Therapy and Sargramostim Compared With Placebo and Sargramostim Following Rituximab in Treating Patients With Non-Hodgkin's Lymphoma

This study has been terminated.
(Withdrawn as company has shut down and filed for bankruptcy)
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00089115
First received: August 4, 2004
Last updated: August 1, 2013
Last verified: February 2006
  Purpose

RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Vaccines made from a person's cancer cells may make the body build an immune response to kill cancer cells. Colony-stimulating factors such as GM-CSF increase the number of immune cells found in bone marrow and peripheral blood. It is not yet known whether combining rituximab and GM-CSF with vaccine therapy may cause a stronger immune response and kill more cancer cells.

PURPOSE: This randomized phase III trial is studying giving rituximab and GM-CSF together with vaccine therapy and comparing it to giving rituximab and GM-CSF alone in treating patients with newly diagnosed, relapsed, or refractory B-cell non-Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine
Biological: rituximab
Biological: sargramostim
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Phase III, Randomized, Double Blind, Placebo-Controlled Trial of Favldand GM-CSF Versus Placebo and GM-CSF Following Rituximab in Subjects With Follicular B-Cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to progression after 248 patients have progressed [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate improvement after 248 patients have progressed [ Designated as safety issue: No ]
  • Overall complete response rate by modified Cheson Criteria after 248 patients have progressed [ Designated as safety issue: No ]
  • Duration of response by modified Cheson Criteria after 248 patients have progressed [ Designated as safety issue: No ]
  • Safety by Common Toxicity Criteria (CTC) after 248 patients have progressed [ Designated as safety issue: Yes ]

Study Start Date: July 2004
Detailed Description:

OBJECTIVES:

Primary

  • Compare time to disease progression in patients with grade 1, 2, or 3 follicular B-cell non-Hodgkin's lymphoma who respond (i.e., complete or partial response, or stable disease) to treatment with rituximab and are then treated with sargramostim (GM-CSF) with vs without autologous immunoglobulin idiotype-KLH conjugate vaccine.

Secondary

  • Compare response rate improvement in patients treated with these regimens.
  • Compare overall complete response rate in patients treated with these regimens.
  • Compare duration of response in patients treated with these regimens.
  • Determine the safety of these regimens in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to prior treatment (yes vs no) and response to rituximab during study (complete response [CR] or partial response [PR] vs stable disease [SD]).

All patients receive rituximab IV once weekly for 4 weeks. Five weeks after the last dose of rituximab, patients are assessed for response. Patients with progressive disease are removed from the study and do not undergo randomization. Patients with a CR, PR, or SD are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive autologous immunoglobulin idiotype-KLH conjugate vaccine subcutaneously (SC) on day 1. Patients also receive sargramostim (GM-CSF) SC on days 1-4.
  • Arm II: Patients receive placebo SC on day 1. Patients also receive GM-CSF SC on days 1-4.

In both arms, treatment repeats monthly for 6 months in the absence of unacceptable toxicity or clinically significant progressive disease. After the first 6 months, patients with a CR, PR, or SD may continue to receive treatment (per treatment arm as above) every 2 months for 1 year (total of 6 doses) and then every 3 months thereafter in the absence of disease progression.

Patients are followed every 3 months for 2 years and then every 6 months until disease progression.

PROJECTED ACCRUAL: A total of 342 evaluable patients (171 per treatment arm) will be accrued for this study within 18 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed follicular B-cell non-Hodgkin's lymphoma (NHL)

    • Grade 1, 2, or 3
  • Meets 1 of the following criteria for treatment with rituximab:

    • Treatment naïve
    • Relapsed or refractory disease after prior chemotherapy
    • Relapsed after a prior documented response (i.e., complete or partial response) to rituximab of at least 6 months duration
  • Tumor accessible for biopsy OR existing biopsy material (taken within the past 6 months) suitable for vaccine preparation
  • Measurable or evaluable disease after tumor tissue procurement for vaccine production
  • No more than 2 prior treatment regimens for NHL

    • Single regimens include any of the following:

      • Maintenance rituximab
      • Rituximab administered once weekly for 8 courses
      • Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab* NOTE: *CHOP followed by rituximab at time of relapse is considered 2 treatment regimens
  • No history of CNS lymphoma or meningeal lymphomatosis

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 75,000/mm^3 (unless related to bone marrow involvement by lymphoma)
  • Hemoglobin ≥ 10g/dL

Hepatic

  • Not specified

Renal

  • Not specified

Cardiovascular

  • No congestive heart failure

Pulmonary

  • No compromised pulmonary function

Immunologic

  • HIV negative
  • No prior allergic response to GM-CSF
  • No active bacterial, viral, or fungal infection

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No psychiatric disorder that would preclude study participation
  • No other malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No other serious nonmalignant disease that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • See Chemotherapy
  • At least 4 weeks since prior immunotherapy
  • No prior radiolabeled anti-lymphoma antibody (e.g., iodine I 131 tositumomab or ibritumomab tiuxetan)
  • No prior autologous or allogeneic stem cell transplantation
  • No prior lymphoma-specific idiotype immunotherapy (e.g., Id vaccine)
  • No prior investigational vaccine or immunotherapeutic containing keyhole limpet hemocyanin (KLH)

Chemotherapy

  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy
  • More than 9 months since prior fludarabine
  • More than 2 years since prior chemotherapy/rituximab combination therapy (e.g., CHOP/rituximab or cyclophosphamide, vincristine, and prednisone [CVP]/rituximab)
  • No more than 6 total prior treatment courses with fludarabine

Endocrine therapy

  • No concurrent steroids for allergic reaction to sargramostim (GM-CSF)

Radiotherapy

  • See Biologic therapy
  • At least 4 weeks since prior radiotherapy

Surgery

  • Not specified

Other

  • At least 4 weeks since prior experimental therapy
  • No concurrent systemic immunosuppressive therapy
  • No other concurrent anti-lymphoma therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00089115

  Show 60 Study Locations
Sponsors and Collaborators
Favrille
Investigators
Study Chair: John F. Bender, PharmD Favrille
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00089115     History of Changes
Other Study ID Numbers: FAV-ID-06, CDR0000378046, FAV-WIRB-20040335, CWRU-FVID-1404
Study First Received: August 4, 2004
Last Updated: August 1, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Immunoglobulins
Immunoglobulin Idiotypes
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 18, 2014