- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00046852
Chemotherapy and Peripheral Stem Cell Transplantation Followed By Immunotherapy in Treating Patients With Multiple Myeloma
High-Dose Therapy and Autologous Blood Stem Cell Transplantation (ASCT) Followed by Post-Transplant Immunotherapy With Costimulated Autologous T-Cells in Conjunction With Pneumococcal Conjugate Vaccine Immunization for Patients With Multiple Myeloma
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous peripheral stem cell transplantation and immunotherapy may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing.
PURPOSE: Randomized phase I/II trial to study the effectiveness of combining chemotherapy with peripheral stem cell transplantation followed by immunotherapy in treating patients who have multiple myeloma.
Study Overview
Status
Intervention / Treatment
- Drug: cyclophosphamide
- Procedure: peripheral blood stem cell transplantation
- Biological: filgrastim
- Drug: melphalan
- Drug: carmustine
- Procedure: bone marrow ablation with stem cell support
- Biological: therapeutic autologous lymphocytes
- Biological: therapeutic tumor infiltrating lymphocytes
- Biological: pneumococcal polyvalent vaccine
Detailed Description
OBJECTIVES:
- Determine the feasibility of expanding ex vivo autologous T cells and infusing these cells after high-dose chemotherapy and autologous peripheral blood stem cell rescue in patients with multiple myeloma.
- Determine the response rate and progression-free survival of patients who receive anti-CD3/anti-CD28 expanded autologous T cells on either day 14 or day 100 post-transplantation.
- Compare response and survival rates of these patients to historical controls.
- Determine the optimal schedule for pneumococcal conjugate vaccine (PCV) to induce an anti-pneumococcal immune response post-transplantation in these patients.
- Determine whether "vaccine education" of antigen-presenting cells (APCs) in the stem cell graft results in an earlier and/or enhanced immune response than with a graft containing "non-educated" APCs in these patients.
- Determine whether an infusion of T cells presensitized to the PCV and expanded ex vivo contributes to the anti-pneumococcal immune response in these patients.
OUTLINE: This is a randomized, multicenter study.
Patients receive cyclophosphamide IV over 12 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 2. Patients undergo leukapheresis to collect mononuclear cells for autologous T cells (ATCs) and peripheral blood stem cells (PBSCs). ATCs are generated by ex vivo expansion for 8-14 days and selection for CD3+/CD28+ cells.
Patients then receive high-dose therapy comprising carmustine IV over 2 hours on day -2 and melphalan IV over 20 minutes on day -1 or melphalan IV alone on days -2 and -1 (or day -1 only). Autologous PBSCs are reinfused on day 0. Patients also receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
Patients who choose to receive pneumococcal conjugate vaccine (PCV) are randomized to 1 of 4 treatment arms.
- Arm I: Patients receive PCV intramuscularly prior to transplantation (10-14 days before lymphocyte collection) and post-transplantation (1 and 3 months) plus costimulated ATCs IV over 20-60 minutes around day 12-14 post-transplantation.
- Arm II: Patients receive PCV as in arm I but receive ATCs around day 100 post-transplantation.
- Arm III: Patients receive PCV post-transplantation only (at 1 and 3 months) plus ATCs as in arm I.
- Arm IV: Patients receive PCV as in arm III and ATCs as in arm II. Patients who choose not to receive the PCV receive ATCs on about day 12-14 after PBSC transplantation.
All patients are offered standard pneumococcal polysaccharide vaccine at 12 months.
Patients are followed twice weekly until day 60, weekly for 4 months, monthly for 6 months, and then every 3 months thereafter.
PROJECTED ACCRUAL: A total of 16-46 patients will be accrued for this study within 14 months.
Study Type
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21201
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104-4283
- Abramson Cancer Center of the University of Pennsylvania
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
- Diagnosis of multiple myeloma requiring systemic treatment
- No obvious myelodysplastic changes in the marrow
PATIENT CHARACTERISTICS:
Age
- 18 to 80
Performance status
- ECOG 0-2 (ECOG 3-4 allowed if based solely on bone pain)
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- No chronic active hepatitis
- No liver cirrhosis
Renal
- Creatinine no greater than 3.0 mg/dL
- No dialysis
Cardiovascular
- LVEF at least 45% unless no evidence of untreated clinically significant functional impairment
Pulmonary
- FEV_1 and FVC at least 50% of predicted
- Total lung capacity at least 50% of predicted
- DLCO at least 50% of predicted
- Mild to moderate pulmonary impairment (lower DLCO) allowed but patients would not receive study carmustine
- Patients unable to complete pulmonary function test due to bone pain or fracture must have high-resolution CT scan of the chest and arterial partial pressure of oxygen greater than 70
Other
- No active infections requiring IV antibiotics
- HIV negative
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- Not specified
Endocrine therapy
- Prior pulse dexamethasone (1-2 courses) allowed
- Concurrent pulse dexamethasone allowed during mobilization therapy
Radiotherapy
- Not specified
Surgery
- Not specified
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Aaron P. Rapoport, MD, University of Maryland Greenebaum Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
- Heptavalent Pneumococcal Conjugate Vaccine
- Melphalan
- Carmustine
Other Study ID Numbers
- CDR0000256870
- MSGCC-0065
- UPCC-6401
- NCI-V02-1709
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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