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

H. Lee Moffitt Cancer Center and Research Institute

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Biological: Autologous Tumor Cell-Based Vaccine; Drug: Cyclophosphamide; Drug: Prednisone; Drug: Dexamethasone; Drug: Doxorubicin; Drug: IL-2; Drug: Vincristine

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00101101

MCC-13840

0406-654 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 43 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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43 participants in 1 patient group

Vaccine and Conventional Therapy

Experimental group

Description:

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.

Treatment:

Biological: Autologous Tumor Cell-Based Vaccine

Drug: Vincristine

Drug: IL-2

Drug: Doxorubicin

Drug: Dexamethasone

Drug: Prednisone

Drug: Cyclophosphamide