Universal Granulocyte Macrophage-colony Stimulating Factor (GM-CSF)-Producing and GM.CD40L for Autologous Tumor Vaccine in Mantle Cell Lymphoma
- Conditions
- Lymphoma
- Interventions
- Biological: Autologous Tumor Cell-Based Vaccine
- Registration Number
- NCT00101101
- Brief Summary
RATIONALE: Vaccines made from gene-modified cells and a person's cancer cells may make the body build an effective immune response to kill cancer cells. Interleukin-2 (IL-2) may stimulate the white blood cells to kill cancer cells. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of cancer. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Giving vaccine therapy together with IL-2 after combination chemotherapy may be a more effective treatment for mantle cell lymphoma.
PURPOSE: This phase II trial is studying how well giving vaccine therapy together with IL-2 after combination chemotherapy works in treating patients with relapsed or de novo stage II, stage III, or stage IV mantle cell lymphoma.
- Detailed Description
Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Evaluation for response was performed 1 month after completing chemotherapy, and included computed tomography (CT) scan, bone marrow biopsy, endoscopy, and colonoscopy. Minimal residual disease (MRD) was assessed qualitatively on bone marrow specimens using polymerase chain reaction (PCR) with standardized primers for evaluation for B-cell receptor gene rearrangement. Responses were defined according to revised Cheson criteria. Patients with successful lymph node harvest who had obtained complete or partial response could proceed to bystander vaccination.
The GM.CD40L bystander vaccine administered intradermally into the bilateral axillary and inguinal nodal basins via eight separate injections (0.125 ml / injection). Low dose IL-2 (0.5 x 10\^6 units) was given subcutaneously twice daily for 14 days following vaccination. Patients were restaged with CT and/or CT/PET and bone marrow biopsy every 6 months, beginning from the last date of chemotherapy. Follow-up bone marrow biopsy evaluation included an assessment for MRD as described above. Patients without disease progression or toxicity attributable to the vaccine were eligible for 4 monthly booster vaccines at 12 months and 24 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 43
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Vaccine and Conventional Therapy IL-2 Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity. Vaccine and Conventional Therapy Autologous Tumor Cell-Based Vaccine Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity. Vaccine and Conventional Therapy Doxorubicin Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity. Vaccine and Conventional Therapy Cyclophosphamide Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity. Vaccine and Conventional Therapy Vincristine Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity. Vaccine and Conventional Therapy Prednisone Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity. Vaccine and Conventional Therapy Dexamethasone Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Rate of Immunological Response to Vaccination 4 months per participant Immunological response to vaccination, as measured by in vitro testing of peripheral blood mononuclear cells (PBMCs) for interferon gamma secretion, delayed type hypersensitivity reaction (DTH) in response to irradiated autologous tumor cells, and lymphocyte accumulation at DTH and vaccine injection sites.
DTH Skin Testing was performed within 2 weeks prior to first vaccine, and again after fourth vaccine was administered. Aliquots containing 10\^6 irradiated autologous tumor cells were re-suspended in 0.2 mL of Plasma-Lyte A and injected intradermally in the forearm and marked. 48 hours later, injection site was inspected for induration and erythema.
3mm punch biopsy of DTH injection site and vaccine site was obtained 48 hours after administration of irradiated tumor cells before and after the vaccine series. Vaccine site biopsy was obtained 2-5 days after the second vaccine had been given. Granulocytic and lymphocytic accumulation at these sites was graded by a pathologist.
- Secondary Outcome Measures
Name Time Method Occurrence of Related Serious Adverse Events (SAEs) 4 months per participant Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase. This included clinical and laboratory evaluation (CBC, blood urea nitrogen (BUN), creatinine, electrolytes, liver function test (LFT), and serum LDH). Toxicity was defined according to the NCI Common Terminology Criteria for Adverse Events (CTCAE-3) Version 3.0 (www.ctep.cancer.gov). Grade 3 or higher SAEs attributed to vaccination: Toxicity was assessed in the 23 patients who received at least one vaccine injection.
Median Event Free Survival (EFS) 18 months Vaccine Response - EFS among participants who received vaccination. Event free survival (EFS) was calculated from date of enrollment until progression or death from any cause. Progressive disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Trial Locations
- Locations (1)
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States