Chemotherapy Plus Vaccination to Treat Mantle Cell Lymphoma

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00005780

Collaborator

(none)

Enrollment

Location

Arm

252.5

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Mantle Cell Lymphoma Lymphoma, Mantle Cell	Drug: EPOCH-R Biological: GM-CSF Biological: Idiotype vaccine	Phase 2

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 1000/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.

Study Design

Study Type:

Interventional

Actual Enrollment :

26 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pilot Study of Idiotype Vaccine and EPOCH-Rituximab Chemotherapy in Untreated Mantle Cell Lymphoma

Actual Study Start Date :

Jun 1, 2000

Actual Primary Completion Date :

Jun 1, 2016

Actual Study Completion Date :

Jun 16, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 EPOCH-R followed by idiotype vaccine and GM-CSF	Drug: EPOCH-R EPOCH-R for 6 cycles Biological: GM-CSF GM-CSF monthly with the vaccine for 5 doses Biological: Idiotype vaccine 1 injection of vaccine monthly for 5 doses

Arm

Intervention/Treatment

Experimental: 1

EPOCH-R followed by idiotype vaccine and GM-CSF

Drug: EPOCH-R

EPOCH-R for 6 cycles

Biological: GM-CSF

GM-CSF monthly with the vaccine for 5 doses

Biological: Idiotype vaccine

1 injection of vaccine monthly for 5 doses

Outcome Measures

Primary Outcome Measures

Progression-free survival [Time of Progressive Disease]
The time from start of treatment until disease progression will be calculated.

Secondary Outcome Measures

response rate of EPOCH-R [36 months]
percentage of patients whose cancer shrinks or disappears after treatment with EPOCH-R

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.