Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma
Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy. Sometimes the transplanted cells are rejected by the body's tissues. Peripheral stem cell transplantation with the person's own stem cells followed by donor peripheral stem cell transplantation may prevent this from happening.
PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy with autologous peripheral stem cell transplantation and donor peripheral stem cell transplantation in treating patients who have multiple myeloma.
Description
OBJECTIVES:
- Determine the incidence of early mortality in patients with multiple myeloma treated with melphalan and autologous peripheral blood stem cell (PBSC) transplantation followed by fludarabine, cyclophosphamide, and allogeneic PBSC transplantation.
- Determine the incidence of early allogeneic graft failure (before day 100 after allogeneic PBSC transplantation) and the incidence of severe acute graft-versus-host disease (GVHD) in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
- Determine the overall and disease-free survival of patients treated with this regimen.
- Correlate changes in the T-cell population with clinical outcome, such as survival, in patients treated with this regimen.
- Correlate changes in the T-cell population with the incidence of GVHD, use of immunosuppressive agents, and effects of fludarabine in patients treated with this regimen.
- Determine the degree of chimerism after allogeneic PBSC transplantation and the time course over which it is established in patients treated with this regimen.
OUTLINE: This is a multicenter study.
Patients receive melphalan IV over 15 minutes on day -1. Autologous peripheral blood stem cells (PBSCs) are reinfused on day 0. Patients also receive sargramostim (GM-CSF) subcutaneously (SC) or IV over at least 30 minutes daily beginning on day 1 and continuing until blood counts recover. Beginning 100-182 days after autologous PBSC transplantation, patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -3 and -2. Allogeneic PBSCs are infused on day 0. Patients may receive a second allogeneic PBSC infusion on day 1. Patients also receive GM-CSF SC or IV over at least 30 minutes daily beginning on day 1 and continuing until blood counts recover. Cyclosporine is administered IV or orally twice daily as graft-versus-host disease (GVHD) prophylaxis, beginning on day -1 and continuing until day 60, followed by a taper in the absence of GVHD.
Patients are followed for 5 years.
PROJECTED ACCRUAL: A total 19-46 patients will be accrued for this study within 3 years.
Study Design
Masking: Open Label, Primary Purpose: Treatment
Conditions
Multiple Myeloma and Plasma Cell Neoplasm
Intervention
sargramostim, cyclophosphamide, cyclosporine, fludarabine phosphate, melphalan, peripheral blood stem cell transplantation
Location
Baptist Cancer Institute - Jacksonville
Jacksonville
Florida
United States
32207-8554
Status
Completed
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00014508
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Melphalan
An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.
Cyclophosphamide
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.
Peripheral Blood Stem Cell Transplantation
Transplantation of stem cells collected from the peripheral blood. It is a less invasive alternative to direct marrow harvesting of hematopoietic stem cells. Enrichment of stem cells in peripheral blood can be achieved by inducing mobilization of stem cells from the BONE MARROW.
Transketolase
An enzyme of the transferase class that catalyzes the conversion of sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to D-ribose 5-phosphate and D-xylulose 5-phosphate in the PENTOSE PHOSPHATE PATHWAY. (Dorland, 27th ed) EC 2.2.1.1.
Transaldolase
An enzyme of the transferase class that catalyzes the reaction sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to yield D-erythrose 4-phosphate and D-fructose phosphate in the PENTOSE PHOSPHATE PATHWAY. (Dorland, 27th ed) EC 2.2.1.2.
Clinical Trials
RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It als...
RATIONALE: Giving low doses of chemotherapy, such as melphalan and fludarabine, and a monoclonal antibody, such as alemtuzumab, before a donor bone marrow or peripheral blood stem cell tra...
RATIONALE: Giving chemotherapy, such as fludarabine and melphalan, before a donor peripheral blood stem cell transplant helps stop the growth of tumor cells. It also stops the patient's im...
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy drugs, such as fludarabine phosphate and melphalan, an...
RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps st...
PubMed Articles
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We have recently shown that lymphocyte and monocyte recovery by day +100 are associated with survival post myeloablative allogeneic hematopoietic transplant for acute leukemia. We hypothesized that ly...
Abstract The increase of fludarabine-resistant chronic lymphocytic leukemia (CLL) presents a new treatment challenge. The aim of this review is to evaluate the efficacy and safety of rituximab for p...
Renal impairment (RI) is a frequent complication with higher incidence of infections and an important prognostic factor for survival. Melphalan clearance is renal function dependent whereas cyclophosp...
The adverse effects of melphalan and cyclophosphamide on hematopoietic stem cells are well-known; however, the effects on the mesenchymal stem cells (MSCs) residing in the bone marrow are less well ch...
