Clinical trial NCT00005780: Chemotherapy Plus Vaccination to Treat Mantle Cell Lymphoma
Official title: Pilot Study of Idiotype Vaccine and EPOCH-Rituximab Chemotherapy in Untreated Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mantle Cell Lymphoma
Lymphoma, Mantle Cell
Keywords: Lymphoma Vaccines
Immune Response Against Lymphoma
Molecular Complete Remissions
Novel Treatment Approach
Mantle Cell Lymphoma
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2000-06-05
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 granulocyte colony-stimulating factor (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 granulocyte-macrophage colony-stimulating factor (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 etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (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.
* Eastern Cooperative Oncology Group (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 study is closed as of 4/18/2022.

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.

Eastern Cooperative Oncology Group (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; absolute neutrophil count (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 multigated acquisition (MUGA) scan is obtained, the left ventricular ejection fraction (LVEF) should exceed 40%.

Ability to give informed consent.

EXCLUSION CRITERIA:

Antibodies to human immunodeficiency virus (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.

Primary outcomes:
measure: Median Progression-free Survival (PFS) in Participants Treated With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (EPOCH-R)
timeFrame: From participants on study date until date of disease relapse or progression, death, or date of last follow-up, assessed up to 245.8 months
measure: Percentage of Participants With an Antibody Response to Idiotype Vaccine
timeFrame: Weeks 12 to 32
Secondary outcomes:
measure: Percentage of Participants Whose Cancer Shrinks or Disappears After Treatment With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (EPOCH-R)
timeFrame: After 6 cycles of EPOCH-R therapy, an average of 18 weeks
measure: Percentage of Participants With Grade 3 or Higher Serious and/or Non-serious Toxicity That Occurred That is at Least Possibly Related to Drug or Vaccine
timeFrame: Up to 30 days after last intervention, up to 12.5 months or 1.04 years
measure: Overall Survival (OS)
timeFrame: Time from treatment start date until date of death or date last follow-up, up to 250 months
measure: Progression Free Survival (PFS) in Participants Who Received Idiotype Vaccine
timeFrame: Time from treatment start date until date of disease relapse or progression, death, or date last follow-up, an average of 25 months
measure: Percentage of Participants With Antibodies to Keyhole Limpet Haemocyanin (KLH)
timeFrame: After vaccinations administered at 0, 1, 2, 3 and 5 months
measure: Percentage of Participants With Induction of Type 1 Cytokine T-cell Response
timeFrame: After vaccinations administered at 0, 1, 2, 3 and 5 months
measure: Time to Recovery of CD4 T Lymphocytes (CD4+)
timeFrame: After chemotherapy before vaccination, up to 6 months
Other outcomes:
measure: Here is the Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0).
timeFrame: Up to 30 days after last intervention, up to 12.5 months or 1.04 years
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Christopher J Melani, M.D.
role: PRINCIPAL_INVESTIGATOR
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