Rituximab and Cyclophosphamide Followed by Vaccine Therapy in Treating Patients With Relapsed Hodgkin Lymphoma

NCT ID: NCT00134082

Last Updated: 2019-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2013-01-31

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing. Vaccines made from another person's cancer cells may help the body build an effective immune response to kill cancer cells. Giving rituximab together with chemotherapy and vaccine therapy may kill more cancer cells

PURPOSE: This phase I/II trial is studying how well giving rituximab together with cyclophosphamide and vaccine therapy works in treating patients with relapsed Hodgkin lymphoma.

Detailed Description

OBJECTIVES:

Primary

• Determine the safety and tolerability of rituximab and high-dose cyclophosphamide followed by vaccine therapy comprising an allogeneic vaccine that expresses Hodgkin's tumor antigens and sargramostim (GM-CSF) (KGEL vaccine) as salvage therapy in patients with relapsed Hodgkin lymphoma.
• Determine the immunologic response to this vaccine in these patients.

Secondary

• Determine the 3-year relapse-free and overall survival of patients treated with this regimen.
• Determine the patterns of cellular immune reconstitution in patients treated with this regimen.

OUTLINE: This is an open-label study.

Patients receive rituximab IV on days -10 and -7 and then on days 29, 36, 43, and 50 (weeks 4-7) and high-dose (transplant-dose) cyclophosphamide IV on days -3 to 0 without stem cell rescue. Patients receive filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover. Patients also receive vaccine therapy comprising an allogeneic vaccine that expresses Hodgkin's tumor antigens and sargramostim (GM-CSF) (KGEL vaccine) intradermally on day 1, and weeks 4, 8, 12, 16, and 24.

After completion of high-dose cyclophosphamide, patients are followed every 3 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 25 patients will be accrued for this study.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Immunotherapy

All participants received two days of rituximab, then four days of high-dose cyclophosphamide followed by filgrastim. Participants then received six doses of KGEL vaccine over 24 weeks interspersed with four additional doses of rituximab.

Group Type: EXPERIMENTAL

KGEL vaccine

Intervention Type: BIOLOGICAL

Vaccine was administered at weeks 0, 4, 8, 12, 16, and 24 at a dose of 1 x 10\^8 cells per dose. The first dose was given on Day +1.

Filgrastim

Intervention Type: BIOLOGICAL

5 mcg/kg/day starting on Day +6 until ANC is \>= 1000/mcL.

Rituximab

Intervention Type: BIOLOGICAL

375 mg/m\^2/day on Days -10, -7, and at weeks 4, 5, 6, and 7.

Cyclophosphamide

Intervention Type: DRUG

50 mg/kg/day on Day -3, -2, -1, and 0.

Interventions

KGEL vaccine

Vaccine was administered at weeks 0, 4, 8, 12, 16, and 24 at a dose of 1 x 10\^8 cells per dose. The first dose was given on Day +1.

Intervention Type: BIOLOGICAL

Filgrastim

5 mcg/kg/day starting on Day +6 until ANC is \>= 1000/mcL.

Intervention Type: BIOLOGICAL

Rituximab

375 mg/m\^2/day on Days -10, -7, and at weeks 4, 5, 6, and 7.

Intervention Type: BIOLOGICAL

Cyclophosphamide

50 mg/kg/day on Day -3, -2, -1, and 0.

Intervention Type: DRUG

Other Intervention Names

G-CSF; Rituxan; Cytoxan

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed classical Hodgkin's lymphoma
• Relapsed disease with achievement of at least a partial response or a metabolic response to most recent salvage therapy

• No primary induction failure, defined as disease progression during or within 2 months after completion of first-line therapy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 75,000/mm^3

Hepatic

• Bilirubin ≤ 2.0 mg/dL* NOTE: *Unless due to lymphoma or Gilbert's syndrome

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• Ejection fraction ≥ 45% by echocardiogram or MUGA

Pulmonary

• DLCO ≥ 50% of predicted (corrected for alveolar volume)

Immunologic

• No known HIV positivity
• No active infection requiring oral or IV antibiotics
• No autoimmune or other disease requiring long-term systemic steroids or other long-term immunosuppressants

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to tolerate high-dose therapy
• No other malignancy within the past 3 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior bone marrow transplantation

Endocrine therapy

• Not specified

Radiotherapy

• Concurrent radiotherapy for disease progression after high-dose cyclophosphamide allowed at the discretion of the principal investigator

Surgery

• Not specified

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Ambinder, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

P50CA096888

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NA_00035358

Identifier Type: OTHER

Identifier Source: secondary_id

J0528

Identifier Type: -

Identifier Source: org_study_id