Chemotherapy Plus Vaccination to Treat Mantle Cell Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00005780
First received: June 3, 2000
Last updated: March 14, 2014
Last verified: December 2013
  Purpose

This study will evaluate the safety and effectiveness of an experimental cancer vaccine for mantle cell lymphoma a form of cancer of the white blood cells called lymphocytes. Although standard treatments for lymphoma may achieve disease remission, none provides a cure.

Patients with mantle cell lymphoma 18 years and older who have not been treated previously with chemotherapy may participate in this study. Candidates will be screened for eligibility with a medical history and physical examination. Other tests that may be required include blood and urine tests; lung function studies; imaging tests such as magnetic resonance imaging, computed tomography and X-rays; and biopsy (surgical removal of a small tissue sample) of tumor, bone marrow, or other tissue.

Patients enrolled in the study will begin treatment with chemotherapy designed to reduce disease to a minimum that is, to achieve remission or shrink the tumor as much as possible. Chemotherapy will be administered on an outpatient basis over a period of around 12 to 18 weeks in 3-week cycles as follows: prednisone by mouth on days 1 through 5; etoposide, doxorubicin and vincristine intravenously through (a vein) on days 1 through 5; and cyclophosphamide intravenously on day 5. Starting day 6, patients receive no chemotherapy for 16 days. In addition, an antibody called rituximab, which attaches to lymphoma cells and may increase the effectiveness of the chemotherapy, will be given on day 1 of the cycle. Patients will also receive a protein called G-CSF starting day 6 of the cycle and continuing until the white blood cell count recovers or until day 19. G-CSF is naturally produced by bone marrow and may boost the immune system. The chemotherapy drugs and rituximab are infused through a vein by means of a lightweight portable pump, which patients are taught how to use. Patients are also how taught how to give themselves G-CSF injections under the skin, similar to insulin injections.

The first vaccination will be given at least 3 months after chemotherapy ends and will be repeated every 4 weeks for a maximum of 5 vaccinations. The vaccinations will be given in the clinic. Patients will also receive daily injections of GM-CSF, a growth factor naturally produced by bone marrow that can boost the immune system. These injections will be given the day of the vaccination and for the next 3 days.

When vaccine therapy is completed, patients who were treated successfully will be followed with periodic clinic visits for follow-up examinations and tests. Patients in whom the lymphoma did not disappear entirely or who have a recurrence of disease will be advised of further treatment possibilities.


Condition Intervention Phase
Mantle Cell Lymphoma
Drug: Rituximab
Drug: autologous tumor cell vaccine
Drug: doxorubicin
Drug: cyclophosphamide
Drug: etoposide
Drug: filgrastim
Drug: keyhole limpet hemocyanin
Drug: prednisone
Drug: sargramostim
Drug: vincristine
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Pilot Study of Idiotype Vaccine and EPOCH-Rituximab Chemotherapy in Untreated Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 26
Study Start Date: June 2000
Study Completion Date: January 2014
Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Rituximab
    N/A
    Drug: autologous tumor cell vaccine
    N/A
    Drug: doxorubicin
    N/A
    Drug: cyclophosphamide
    N/A
    Drug: etoposide
    N/A
    Drug: filgrastim
    N/A
    Drug: keyhole limpet hemocyanin
    N/A
    Drug: prednisone
    N/A
    Drug: sargramostim
    N/A
    Drug: vincristine
    N/A
Detailed Description:

Background:

  • Mantle cell lymphoma presents a particular clinical challenge because it is aggressive and incurable with chemotherapy. Thus, novel treatment approaches are needed.
  • In follicular center cell lymphomas, another incurable disease, recent evidence suggests that molecular complete remissions may be achieved following idiotype vaccination in patients who have achieved minimal residual disease with combination chemotherapy.
  • These results suggest that idiotype vaccines may be able to induce a clinically significant immune response against lymphoma.

Objectives:

  • To assess if EPOCH-R/idiotype vaccination is associated with a median progression-free survival consistent with 36 months;
  • To assess if rituximab affects generation of T-cell immunity against the idiotype.
  • To compare T-cell immunity using two different methods of isolating the idiotype protein.

Eligibility:

  • Tissue diagnosis of mantle cell lymphoma.
  • Age greater than or equal to 18 years.
  • Previously untreated with cytotoxic chemotherapy. All stages of disease.
  • Lymph node of greater than or equal to 2 cm accessible for biopsy/harvest or greater than 000/microl of circulating tumor cells in the blood. ECOG performance status less than or equal to 3.

Design:

  • In the present study, we propose to investigate the efficacy of idiotype vaccine treatment in previously untreated patients with mantle cell lymphomas. In order to achieve minimal residual disease, patients will receive 6 cycles EPOCH chemotherapy and rituximab (EPOCH-R) followed by 5 idiotype vaccine injections.
  • This study has completed accrual of 26 patients and is only open for follow-up.
  Eligibility

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

Tissue diagnosis of mantle cell lymphoma (confirmed in Laboratory of Pathology). Blastic cell variant will be eligible.

Age greater than or equal to 18.

Previously untreated with cytotoxic chemotherapy. Patients may have received local radiation or a short course of steroids for control of symptoms.

All stages of disease.

Lymph node of greater than or equal to 2 cm accessible for biopsy/harvest or greater than 1000/microliters of circulating tumor cells in the blood.

ECOG performance status of less than or equal to 3.

Adequate major organ function (serum creatinine 1.5 mg/dl or creatinine clearance greater than 60 ml/min; bilirubin less than 2 mg/dl (total) except less than 5 mg/dl in patients with Gilbert's syndrome as defined by greater than 80% unconjugated; ANC greater than 1000 and platelets greater than 100,000) unless impairment due to organ involvement by lymphoma.

No active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year. If MUGA is obtained, the LVEF should exceed 40%.

Ability to give informed consent.

EXCLUSION CRITERIA:

Antibodies to HIV or presence of hepatitis B surface antigen.

Pregnant or lactating.

Prior malignancy in past 5 years except squamous or basal cell carcinoma or curatively treated in situ of the cervix.

Involvement of central nervous system by lymphoma.

  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: NCT00005780

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Wyndham H Wilson, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT00005780     History of Changes
Obsolete Identifiers: NCT00020215
Other Study ID Numbers: 000133, 00-C-0133
Study First Received: June 3, 2000
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Monoclonal Antibody
Non-Hodgkin's Lymphoma
Mantle Cell Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Doxorubicin
Etoposide
Prednisone
Vincristine
Keyhole-limpet hemocyanin
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 24, 2014