Chemotherapy Plus Vaccination to Treat Mantle Cell Lymphoma

January 4, 2023 updated by: Christopher Melani, MD, National Cancer Institute (NCI)

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

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....

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab
Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) followed by idiotype vaccine and granulocyte-macrophage colony-stimulating factor (GM-CSF).
Drug: EPOCH-R
EPOCH-R for 6 cycles
Other Names:
  • Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab
Biological: GM-CSF
Granulocyte-macrophage colony-stimulating factor (GM-CSF) monthly with the vaccine for 5 doses
Other Names:
  • Sargramostim
Biological: Idiotype vaccine
1 injection of vaccine monthly for 5 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Progression-free Survival (PFS) in Participants Treated With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (EPOCH-R)
Time Frame: 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
PFS is time from on study date until disease relapse or progression, death, or date of last follow-up. Progression was measured by the International Workshop to Standardize Response Criteria for non-Hodgkin's Lymphoma and is defined as ≥50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously involved node or the appearance of any new lesion.
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
Percentage of Participants With an Antibody Response to Idiotype Vaccine
Time Frame: Weeks 12 to 32
Participants with an immune response to idiotype vaccine measured by enzyme-linked immunosorbent assay (ELISA) to detect antibody binding to tumor cells. Positive response was defined as at least a fourfold increase in antibody titer.
Weeks 12 to 32

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Whose Cancer Shrinks or Disappears After Treatment With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (EPOCH-R)
Time Frame: After 6 cycles of EPOCH-R therapy, an average of 18 weeks
Response was measured by the International Workshop to Standardize Response Criteria for non-Hodgkin's Lymphoma. Complete Response (CR) is a complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., Lactate dehydrogenase (LDH) definitely assignable to the lymphoma. Complete Response Unconfirmed (CRu) is as per CR criteria except that if a residual node is > 1.5cm, it must have regressed by > 75% in the sum of the products of the greatest diameters (SPD). Partial Response (PR) is ≥50% decreased in the SPD of 6 largest dominant nodes or nodal masses. Stable Disease (SD) is defined as less than a PR but not progressive disease. Progression is ≥50% increase from nadir in the SPD of any previously involved node or the appearance of any new lesion.
After 6 cycles of EPOCH-R therapy, an average of 18 weeks
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
Time Frame: Up to 30 days after last intervention, up to 12.5 months or 1.04 years
Serious and/or non-serious adverse events were assessed by the Common Toxicity Criteria (CTC v2.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.
Up to 30 days after last intervention, up to 12.5 months or 1.04 years
Overall Survival (OS)
Time Frame: Time from treatment start date until date of death or date last follow-up, up to 250 months
OS was determined by the Kaplan-Meier method and is defined as the time from treatment start date until date of death or last follow-up.
Time from treatment start date until date of death or date last follow-up, up to 250 months
Progression Free Survival (PFS) in Participants Who Received Idiotype Vaccine
Time Frame: Time from treatment start date until date of disease relapse or progression, death, or date last follow-up, an average of 25 months
PFS is defined as the time from start of treatment until disease relapse or progression, death, or last follow-up. Progression was measured by the International Workshop to Standardize Response Criteria for non-Hodgkin's Lymphoma and is defined as ≥50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously involved node or the appearance of any new lesion
Time from treatment start date until date of disease relapse or progression, death, or date last follow-up, an average of 25 months
Percentage of Participants With Antibodies to Keyhole Limpet Haemocyanin (KLH)
Time Frame: After vaccinations administered at 0, 1, 2, 3 and 5 months
Participants with an immune response against carrier molecule KLH measured by enzyme-linked immunosorbent assay (ELISA) to detect antibody binding to tumor cells. Positive response was defined as at least a fourfold increase in antibody titer.
After vaccinations administered at 0, 1, 2, 3 and 5 months
Percentage of Participants With Induction of Type 1 Cytokine T-cell Response
Time Frame: After vaccinations administered at 0, 1, 2, 3 and 5 months
Participants with tumor specific T-cell responses during B-cell recovery was assessed in a Clinical Laboratory Improvement Amendments (CLIA) certified lab and were measured by flow cytometry and/or enzyme-linked immunosorbent spot (ELISPOT). A positive response required the response to be at least twice the negative controls.
After vaccinations administered at 0, 1, 2, 3 and 5 months
Time to Recovery of CD4 T Lymphocytes (CD4+)
Time Frame: After chemotherapy before vaccination, up to 6 months
Recovery of CD4+ was measured by flow cytometry. Blood samples were collected via apheresis and analyzed by multicolor flow cytometry in peripheral blood mononuclear cells (PBMCs) for cluster of differentiation 4 (CD4). Time to recovery of CD4 T lymphocytes was defined as the time required for CD4 T lymphocytes to increase above the lower limit of normal of the normal laboratory value range of 359 cells/mcL
After chemotherapy before vaccination, up to 6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Here is the Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0).
Time Frame: Up to 30 days after last intervention, up to 12.5 months or 1.04 years
Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Toxicity Criteria (CTC v2.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Up to 30 days after last intervention, up to 12.5 months or 1.04 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 1, 2000

Primary Completion (ACTUAL)

June 9, 2021

Study Completion (ACTUAL)

June 16, 2021

Study Registration Dates

First Submitted

June 3, 2000

First Submitted That Met QC Criteria

June 3, 2000

First Posted (ESTIMATE)

June 5, 2000

Study Record Updates

Last Update Posted (ACTUAL)

January 31, 2023

Last Update Submitted That Met QC Criteria

January 4, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 000133
  • 00-C-0133

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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