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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Pilot Study of Rituximab, High Dose Cyclophosphamide, and GM-CSF Based Immunotherapy for Relapsed Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: KGEL vaccine
* Biological: Filgrastim
* Biological: Rituximab
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunotherapy<br>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. | Biological: KGEL vaccine<br>* 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.<br>Biological: Filgrastim<br>* 5 mcg/kg/day starting on Day +6 until ANC is >= 1000/mcL.<br>* Other names: G-CSF;Biological: Rituximab<br>* 375 mg/m^2/day on Days -10, -7, and at weeks 4, 5, 6, and 7.<br>* Other names: Rituxan;Drug: Cyclophosphamide<br>* 50 mg/kg/day on Day -3, -2, -1, and 0.<br>* Other names: Cytoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Grade 3-5 Adverse Events | Number of participants who experienced at least one grade 3-5 adverse event by CTCAE 3.0 that was attributed to protocol intervention. | Up to 36 months | 
| Percentage of Participants With an Increase in Frequency of LMP2-specific CD8+ T Cells | Percentage of participants with an increase in frequency of LMP2-specific CD8+ T cells. Increase in frequency is defined as at least one order of magnitude higher than baseline measurement. | Change from 3 months to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Median number of months that participants were alive (overall survival) and alive without disease relapse or new diagnosis of myelodysplasia or acute leukemia (event-free survival). | Up to 6 years | 
| Days to Neutrophil and Platelet Engraftment | Median number of days to absolute neutrophil count (ANC) >= 500/mcL and platelet count >=20000/mcL. | Up to 46 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult Hodgkin lymphoma