Universal Granulocyte Macrophage-colony Stimulating Factor (GM-CSF)-Producing and GM.CD40L for Autologous Tumor Vaccine in Mantle Cell Lymphoma | RxWiki

Universal Granulocyte Macrophage-colony Stimulating Factor (GM-CSF)-Producing and GM.CD40L for Autologous Tumor Vaccine in Mantle Cell Lymphoma

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Lymphoma
Intervention	Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Drug: Dexamethasone Biological: Autologous Tumor Cell-Based Vaccine Drug: IL-2
Phase	Phase 2
Sponsor	H. Lee Moffitt Cancer Center and Research Institute
Responsible Party	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier	NCT00101101
First Received	January 7, 2005
Last Updated	September 9, 2013
Last verified	June 2013

Tracking Information[ + expand ][ + ]

First Received Date	January 7, 2005
Last Updated Date	September 9, 2013
Start Date	July 2004
Estimated Primary Completion Date	December 2014
Current Primary Outcome Measures	Rate of Immunological Response to Vaccination [Time Frame: 4 months per participant] [Designated as safety issue: No]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.
Current Secondary Outcome Measures	Occurrence of Related Serious Adverse Events (SAEs) [Time Frame: 4 months per participant] [Designated as safety issue: Yes]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) [Time Frame: 18 months] [Designated as safety issue: No]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.

Descriptive Information[ + expand ][ + ]

Brief Title	Universal Granulocyte Macrophage-colony Stimulating Factor (GM-CSF)-Producing and GM.CD40L for Autologous Tumor Vaccine in Mantle Cell Lymphoma
Official Title	A Phase II Trial Using a Universal GM-CSF-Producing and CD40L-Expressing Bystander Cell Line (GM.CD40L) in the Formulation of Autologous Tumor Cell-Based Vaccines for Patients With Mantle Cell Lymphoma
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.
Study Type	Interventional
Study Phase	Phase 2
Study Design	Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Lymphoma
Intervention	Drug: Cyclophosphamide Participants receive conventional chemotherapy comprising 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. Other Names: CytoxanDrug: Doxorubicin Participants receive conventional chemotherapy comprising 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. Other Names: adriamycin Rubex Drug: Vincristine Participants receive conventional chemotherapy comprising 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. Other Names: Oncovin leurocristine VCR Drug: Prednisone Participants receive conventional chemotherapy comprising 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. Other Names: Deltasone Liquid Pred Meticorten Orasone Drug: Dexamethasone Participants receive conventional chemotherapy comprising 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. Other Names: Decadron Dexasone Diodex Hexadrol Biological: Autologous Tumor Cell-Based Vaccine Participants receive vaccine comprising autologous tumor cells and GM.CD40L intradermally on day 1 and low-dose interleukin-2 (IL-2) subcutaneously twice daily on days 1-14. Treatment repeats every 28 days for 4 courses. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2 as above. Drug: IL-2 Participants receive vaccine comprising autologous tumor cells and GM.CD40L intradermally on day 1 and low-dose interleukin-2 (IL-2) subcutaneously twice daily on days 1-14. Treatment repeats every 28 days for 4 courses. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2 as above. Other Names: interleukin-2 cytokine aldesleukin
Study Arm (s)	Experimental: Vaccine and Conventional Therapy 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.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Active, not recruiting
Estimated Enrollment	43
Estimated Completion Date	December 2014
Estimated Primary Completion Date	October 2012
Eligibility Criteria	DISEASE CHARACTERISTICS: - Histologically confirmed mantle cell lymphoma - Stage II, III, or IV disease - Relapsed or de novo disease - No symptomatic brain metastasis PATIENT CHARACTERISTICS: Age - 18 and over Performance status - Eastern Cooperative Oncology Group (ECOG) 0-2 Life expectancy - Not specified Hematopoietic - White blood count (WBC) > 3,000/mm^3 - Absolute neutrophil count > 1,500/mm^3 - Platelet count > 100,000/mm^3 - Hematocrit > 25% - Hemoglobin > 8 g/dL Hepatic - Bilirubin < 2.0 mg/dL Renal - Creatinine < 2.0 mg/dL OR - Creatinine clearance > 60 mL/min Immunologic - No serious ongoing infection - No known HIV infection - No other pre-existing immunodeficiency condition Other - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception for 1 month before, during, and for 3 months after study treatment PRIOR CONCURRENT THERAPY: Biologic therapy - No other concurrent immunotherapy Chemotherapy - More than 4 weeks since prior chemotherapy - No other concurrent chemotherapy Endocrine therapy - More than 4 weeks since prior steroids - No concurrent corticosteroids except as replacement doses in patients who are hypoadrenal Radiotherapy - More than 2 weeks since prior radiotherapy - No concurrent radiotherapy Surgery - Not specified Other - No other concurrent immunosuppressive therapy
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT00101101
Other Study ID Numbers	MCC-13840
Has Data Monitoring Committee	No
Information Provided By	H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor	H. Lee Moffitt Cancer Center and Research Institute
Collaborators	National Cancer Institute (NCI) Lymphoma Research Foundation Novartis
Investigators	Principal Investigator: Sophie Dessureault, M.D., Ph.D. H. Lee Moffitt Cancer Center and Research Institute
Verification Date	June 2013

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