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

Johns Hopkins Medicine

Status and phase: Completed; Phase 2; Phase 1

Conditions: Lymphoma

Treatments: Biological: KGEL vaccine; Drug: Cyclophosphamide; Biological: Rituximab; Biological: Filgrastim

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00134082

P50CA096888 (U.S. NIH Grant/Contract)

NA_00035358 (Other Identifier)

P30CA006973 (U.S. NIH Grant/Contract)

J0528

Details and patient eligibility

About

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.

Full 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.

Enrollment: 31 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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31 participants in 1 patient group

Immunotherapy

Experimental group

Description:

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.

Treatment:

Biological: Rituximab

Biological: Filgrastim

Drug: Cyclophosphamide

Biological: KGEL vaccine