Chemotherapy Plus Vaccination to Treat Mantle Cell Lymphoma | RxWiki

Chemotherapy Plus Vaccination to Treat Mantle Cell Lymphoma

Overview[ - collapse ][ - ]

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	Mantle Cell Lymphoma
Intervention	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	Phase 2
Sponsor	National Cancer Institute (NCI)
Responsible Party	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier	NCT00005780
First Received	June 3, 2000
Last Updated	March 14, 2014
Last verified	December 2013

Tracking Information[ + expand ][ + ]

First Received Date	June 3, 2000
Last Updated Date	March 14, 2014
Start Date	June 2000
Estimated Primary Completion Date	January 2014
Current Primary Outcome Measures	Not Provided
Current Secondary Outcome Measures	Not Provided

Descriptive Information[ + expand ][ + ]

Brief Title	Chemotherapy Plus Vaccination to Treat Mantle Cell Lymphoma
Official Title	Pilot Study of Idiotype Vaccine and EPOCH-Rituximab Chemotherapy in Untreated Mantle Cell Lymphoma
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.
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.
Study Type	Interventional
Study Phase	Phase 2
Study Design	Primary Purpose: Treatment
Condition	Mantle Cell Lymphoma
Intervention	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
Study Arm (s)	Not Provided

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	26
Estimated Completion Date	January 2014
Estimated Primary Completion Date	August 2005
Eligibility 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.
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT00005780
Other Study ID Numbers	000133
Has Data Monitoring Committee	Not Provided
Information Provided By	National Institutes of Health Clinical Center (CC)
Study Sponsor	National Cancer Institute (NCI)
Collaborators	Not Provided
Investigators	Principal Investigator: Wyndham H Wilson, M.D. National Cancer Institute (NCI)
Verification Date	December 2013

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