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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Lymphoma Research Foundation
Novartis
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00101101
First received: January 7, 2005
Last updated: September 9, 2014
Last verified: September 2014
  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 Intervention Phase
Lymphoma
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone
Drug: Dexamethasone
Biological: Autologous Tumor Cell-Based Vaccine
Drug: IL-2
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

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.



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.


Enrollment: 43
Study Start Date: July 2004
Estimated Study Completion Date: March 2015
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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 Name: Cytoxan
Drug: 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00101101

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612-9497
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Lymphoma Research Foundation
Novartis
Investigators
Principal Investigator: Sophie Dessureault, M.D., Ph.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00101101     History of Changes
Other Study ID Numbers: MCC-13840, 0406-654
Study First Received: January 7, 2005
Results First Received: June 20, 2013
Last Updated: September 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
recurrent mantle cell lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma

Additional relevant MeSH terms:
Lymphoma, Mantle-Cell
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Liposomal doxorubicin
Dexamethasone
Doxorubicin
Prednisone
Interleukin-2
Vincristine
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 22, 2014