Overview

This trial is active, not recruiting.

Conditions refractory multiple myeloma, stage i multiple myeloma, stage ii multiple myeloma, stage iii multiple myeloma
Treatments melphalan, autologous hematopoietic stem cell transplantation, autologous bone marrow transplantation, peripheral blood stem cell transplantation, total-body irradiation, cyclosporine, mycophenolate mofetil, therapeutic allogeneic lymphocytes
Phase phase 1/phase 2
Sponsor Fred Hutchinson Cancer Research Center
Collaborator National Cancer Institute (NCI)
Start date March 1999
End date December 2002
Trial size 40 participants
Trial identifier NCT00003954, 1383.00, NCI-2012-00670, P01CA078902

Summary

In this study donor bone marrow transplantation is divided into a two step process to try to significantly reduce the side effects of the procedure yet still provide patients with multiple myeloma the benefits of this procedure

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 15-20 minutes on day -2. TRANSPLANTATION: Patients undergo autologous bone marrow or PBSCT on day 0. NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0. TRANSPLANTATION: Patients undergo donor PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV BID on days -1 and 0 and PO BID on days 1-80 with taper based on evaluation of disease response and GVHD. Patients also receive mycophenolate mofetil PO BID on days 0-27. POST TRANSPLANT DLI: Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments.
melphalan Alkeran
Given IV
autologous hematopoietic stem cell transplantation
Undergo autologous bone marrow or PBSCT
autologous bone marrow transplantation ABMT
Undergo autologous bone marrow or PBSCT
peripheral blood stem cell transplantation PBPC transplantation
Undergo autologous bone marrow or PBSCT
total-body irradiation TBI
Undergo TBI
peripheral blood stem cell transplantation PBPC transplantation
Undergo donor PBSCT
cyclosporine ciclosporin
Given IV and PO
mycophenolate mofetil Cellcept
Given PO
therapeutic allogeneic lymphocytes ALLOLYMPH
Undergo DLI

Primary Outcomes

Measure
PFS
time frame: From the date of transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission, up to 3 years
Decrease in the short-term transplant-related mortality
time frame: Day 100 after allograft
Establish stable allogeneic engraftment (mixed or full donor chimerism)
time frame: At day 56 after allografting

Secondary Outcomes

Measure
Overall survival
time frame: Up to 3 years
Relapse rate
time frame: Up to 3 years
Response rate
time frame: Up to 3 years
Ability to convert mixed to full donor chimerism with DLI
time frame: Up to 3 years

Eligibility Criteria

Male or female participants up to 65 years old.

Inclusion Criteria: - Meet Salmon and Durie criteria for initial diagnosis of multiple myeloma; transplant will be offered to patients with stage II or III multiple myeloma (MM) at diagnosis or have received chemotherapy and/or radiation therapy for progressive MM after initial diagnosis of stage I disease - The patient must have the capacity to give informed consent - Have received at least 4 cycles of conventional dose chemotherapy for MM - DONOR: HLA genotypically identical sibling - DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis for both peripheral blood stem cell (PBSC) allograft and subsequent DLI - DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian) - DONOR: Age < 75, older donors may be considered after consultation by Psychological Consultation Center (PCC) Exclusion Criteria: - Karnofsky score less than 60, unless due solely to myeloma - Left ventricular ejection fraction less than 40% - Bilirubin greater than 2 X the upper limit of normal - Serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) > 2 X the upper limit of normal - Diffusion lung capacity of carbon monoxide (DLCO) < 50% (corrected) or receiving continuous supplemental oxygen - Patients with poorly controlled hypertension - Pregnancy - Seropositive for the human immunodeficiency virus - Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment - Creatinine clearance < 40 cc/min at the time of initial autografting evaluation - Prior autograft (can be treated on alternative protocol) - DONOR: Identical twin - DONOR: Age less than 12 years - DONOR: Pregnancy - DONOR: Infection with human immunodeficiency virus (HIV) - DONOR: Inability to achieve adequate venous access - DONOR: Known allergy to G-CSF - DONOR: Current serious systemic illness - DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) criteria for stem cell donation as described in the standard practice guidelines of the institution

Additional Information

Official title Allogeneic Stem Cell Transplantation For Multiple Myeloma: A Two Step Approach To Reduce Toxicity Involving High Dose Melphalan and Autologous Stem Cell Transplant Followed By PBSC Allografting After Low Dose TBI
Principal investigator David Maloney
Description PRIMARY OBJECTIVES: I. To evaluate engraftment of human leukocyte antigen (HLA) identical peripheral blood stem cell (PBSC) allografts given after conditioning with total-body irradiation (TBI) (200 cGy) and post-grafting immunosuppression with cyclosporine (CSP)/mycophenolate mofetil (MMF) in myeloma patients initially cytoreduced with high-dose melphalan. II. To evaluate non-relapse mortality at day 100 post allografting. III. To evaluate the efficacy of this allografting strategy in terms of long-term progression free survival (PFS). OUTLINE: CONDITIONING REGIMEN: Patients receive high-dose melphalan intravenously (IV) over 15-20 minutes on day -2. TRANSPLANTATION: Patients undergo autologous bone marrow or PBSC transplantation (PBSCT) on day 0. NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0. TRANSPLANTATION: Patients undergo donor PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV twice daily (BID) on days -1 and 0 and orally (PO) BID on days 1-80 with taper based on evaluation of disease response and graft-versus-host disease (GVHD). Patients also receive mycophenolate mofetil PO BID on days 0-27. POST-TRANSPLANTATION DONOR LYMPHOCYTE INFUSION (DLI): Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments. After completion of study treatment, patients are followed up for 3 years.
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Fred Hutchinson Cancer Research Center.