Universal GM-CSF-Producing and GM.CD40L for Autologous Tumor Vaccine in Mantle Cell Lymphoma
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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, Hyperfractionated Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Drug: Dexamethasone Drug: High-Dose Methotrexate 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 |
- Number of Participants With Anti-Tumor Response [ Time Frame: 6 years ] [ Designated as safety issue: No ]To evaluate patients for the development of specific anti-tumor immune responses after immunization with the autologous tumor cell / GM.CD40L bystander cell vaccine. Immunogenicity will be measured by in vitro testing of peripheral blood lymphocytes (PBLs) for cytokine-secreting T cells in enzyme-linked immunospot (ELISPOT) assays, delayed-type hypersensitivity (DTH) skin testing with irradiated autologous tumor cells, and biopsy of the DTH site for immunohistochemical analysis of infiltrating lymphocytes 48 hours after intradermal injection of autologous tumor cells. Vaccine injection sites will be biopsied to evaluate local response to vaccination.
- Frequency of Toxicity Related to Study Treatment [ Time Frame: 6 years ] [ Designated as safety issue: Yes ]To evaluate the toxicity of the autologous tumor cell / GM.CD40L bystander cell vaccine. Review of adverse events utilizing Common Toxicity Criteria (CTC) V3.
| Enrollment: | 43 |
| Study Start Date: | July 2004 |
| Estimated Study Completion Date: | August 2013 |
| Estimated Primary Completion Date: | August 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Conventional Chemotherapy and Vaccine Therapy
Conventional chemotherapy: Patients 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. Patients who achieve a partial or complete response after completion of chemotherapy proceed to vaccine therapy. Vaccine therapy: Patients 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. Treatment continues in the absence of disease progression or unacceptable toxicity. |
Drug: Cyclophosphamide, Hyperfractionated Cyclophosphamide
Other Name: Cytoxan
Drug: Doxorubicin
Other Names:
Drug: Vincristine
Other Names:
Drug: Prednisone
Other Names:
Drug: Dexamethasone
Other Names:
Drug: High-Dose Methotrexate
Other Names:
Biological: Autologous Tumor Cell-Based Vaccine
A therapeutic agent produced by isolating tumor cells from an individual and processing these tumor cells into a vaccine formulation in vitro; the vaccine is then administered to the individual from whom the tumor cells were isolated.
Drug: IL-2
Other Names:
|
Detailed Description:
OBJECTIVES:
Primary
- Determine the specific anti-tumor immune response in patients with relapsed or de novo stage II, III, or IV mantle cell lymphoma treated with vaccine therapy comprising autologous tumor cells and a sargramostim (GM-CSF)-producing and CD40L-expressing cell line (GM.CD40L) combined with low-dose interleukin-2 after conventional chemotherapy.
- Determine the toxicity of this regimen in these patients.
Secondary
- Determine the tumor response rate, time to progression, disease-free survival, and overall survival of patients treated with this regimen.
OUTLINE: Patients undergo surgical resection of a malignant lymph node to collect autologous tumor cells for vaccine production. Vaccine is formulated by combining equal volumes of irradiated autologous tumor cells and irradiated cells from a cell line that produces sargramostim (GM-CSF) and expresses CD40L (GM.CD40L).
- Conventional chemotherapy: Patients 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. Patients who achieve a partial or complete response after completion of chemotherapy proceed to vaccine therapy.
- Vaccine therapy: Patients 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. Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months until disease progression and then annually thereafter.
PROJECTED ACCRUAL: A total of 40-60 patients will be accrued for this study within 15 months.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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| United States, Florida | |
| H. Lee Moffitt Cancer Center and Research Institute | |
| Tampa, Florida, United States, 33612-9497 | |
| 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 |
| Last Updated: | February 12, 2013 |
| 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 Lymphoma, Mantle-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Cyclophosphamide Methotrexate Dexamethasone Doxorubicin Interleukin-2 Prednisone |
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 May 21, 2013