Refractory Multiple Myeloma, Stage III Multiple Myeloma, Stage II Multiple Myeloma, Stage I Multiple Myeloma
Conditions
Brief 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
Detailed 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.
Interventions
DRUGmelphalan
Given IV
PROCEDUREautologous hematopoietic stem cell transplantation
Undergo autologous bone marrow or PBSCT
PROCEDUREautologous bone marrow transplantation
Undergo autologous bone marrow or PBSCT
PROCEDUREperipheral blood stem cell transplantation
Undergo autologous bone marrow or PBSCT
RADIATIONtotal-body irradiation
Undergo TBI
DRUGcyclosporine
Given IV and PO
DRUGmycophenolate mofetil
Given PO
BIOLOGICALtherapeutic allogeneic lymphocytes
Undergo DLI
Sponsors
National Cancer Institute (NCI)
Fred Hutchinson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS | 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 | The current study will be regarded as potentially efficacious if the observed 3-year PFS rate among all patients treated exceeds 30%. The Kaplan-Meier (KM) estimate of PFS will be used. |
| Decrease in the short-term transplant-related mortality | Day 100 after allograft | — |
| Establish stable allogeneic engraftment (mixed or full donor chimerism) | At day 56 after allografting | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Up to 3 years | Estimated by the method of Kaplan and Meier. Confidence intervals will be estimated. |
| Ability to convert mixed to full donor chimerism with DLI | Up to 3 years | Confidence intervals will be estimated. |
| Relapse rate | Up to 3 years | Summarized using cumulative incidence estimates. Confidence intervals will be estimated. |
| Response rate | Up to 3 years | Confidence intervals will be estimated. |
Countries
Italy, United States
Outcome results
None listed