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

NCT00101101 | Completed Phase 2 Results

• 2 other identifiers: MCC-138400406-654
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Rate of Immunological Response to Vaccination

  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.

  4 months per participant

Secondary Outcomes (2)

• Occurrence of Related Serious Adverse Events (SAEs)

  4 months per participant

• Median Event Free Survival (EFS)

  18 months

Study Arms (1)

Vaccine and Conventional Therapy

EXPERIMENTAL

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

Interventions

Cyclophosphamide DRUG

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.

Also known as: Cytoxan

Vaccine and Conventional Therapy

Doxorubicin DRUG

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.

Also known as: adriamycin, Rubex

Vaccine and Conventional Therapy

Vincristine DRUG

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.

Also known as: Oncovin, leurocristine, VCR

Vaccine and Conventional Therapy

Prednisone DRUG

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.

Also known as: Deltasone, Liquid Pred, Meticorten, Orasone

Vaccine and Conventional Therapy

Dexamethasone DRUG

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.

Also known as: Decadron, Dexasone, Diodex, Hexadrol

Vaccine and Conventional Therapy

Autologous Tumor Cell-Based Vaccine BIOLOGICAL

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.

Vaccine and Conventional Therapy

IL-2 DRUG

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.

Also known as: interleukin-2, cytokine, aldesleukin

Vaccine and Conventional Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• National Cancer Institute (NCI): collaborator
• Lymphoma Research Foundation: collaborator
• Novartis: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612-9497, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Lymphoma; Lymphoma, Mantle-Cell

Interventions

Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; Dexamethasone; Calcium Dobesilate; Interleukin-2; Cytokines; aldesleukin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Interleukins; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Limitations and Caveats

With a median follow-up of 67 months, the median overall survival (OS) has not yet been reached.

Results Point of Contact

• Title: Sophie Dessureault, M.D., Ph.D.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

sophie.dessureault@moffitt.org

813-745-1965

Study Officials

• Sophie Dessureault, M.D., Ph.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2005
• First Posted: January 10, 2005
• Study Start: July 1, 2004
• Primary Completion: October 1, 2012
• Study Completion: June 14, 2021
• Last Updated: August 22, 2023
• Results First Posted: September 4, 2013

Record last verified: 2023-08

Locations

US (1)