Melphalan and Stem Cell Transplant Before Total-Body Irradiation and Donor Stem Cell Transplant in Treating Patients With Stage I-III Multiple Myeloma
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Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
|
Refractory Multiple Myeloma Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma |
Drug: melphalan Procedure: autologous hematopoietic stem cell transplantation Procedure: autologous bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: total-body irradiation Drug: cyclosporine Drug: mycophenolate mofetil Biological: therapeutic allogeneic lymphocytes |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
- 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 ] [ Designated as safety issue: No ]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 [ Time Frame: Day 100 after allograft ] [ Designated as safety issue: No ]
- Establish stable allogeneic engraftment (mixed or full donor chimerism) [ Time Frame: At day 56 after allografting ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Estimated by the method of Kaplan and Meier. Confidence intervals will be estimated.
- Relapse rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Summarized using cumulative incidence estimates. Confidence intervals will be estimated.
- Response rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Confidence intervals will be estimated.
- Ability to convert mixed to full donor chimerism with DLI [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Confidence intervals will be estimated.
| Estimated Enrollment: | 40 |
| Study Start Date: | March 1999 |
| Primary Completion Date: | December 2002 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
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. |
Drug: melphalan
Given IV
Other Names:
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous bone marrow or PBSCT
Procedure: autologous bone marrow transplantation
Undergo autologous bone marrow or PBSCT
Other Names:
Procedure: peripheral blood stem cell transplantation
Undergo autologous bone marrow or PBSCT
Other Names:
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Procedure: peripheral blood stem cell transplantation
Undergo donor PBSCT
Other Names:
Drug: cyclosporine
Given IV and PO
Other Names:
Drug: mycophenolate mofetil
Given PO
Other Names:
Biological: therapeutic allogeneic lymphocytes
Undergo DLI
Other Name: ALLOLYMPH
|
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.
Eligibility| Ages Eligible for Study: | up to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts 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
Contacts and Locations| United States, California | |
| City of Hope | |
| Duarte, California, United States, 91010 | |
| United States, Colorado | |
| University of Colorado | |
| Denver, Colorado, United States, 80217 | |
| United States, Washington | |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
| Italy | |
| University of Torino | |
| Torino, Italy, 10126 | |
| Principal Investigator: | David Maloney | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
More Information
No publications provided
| Responsible Party: | Maloney, David, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
| ClinicalTrials.gov Identifier: | NCT00003954 History of Changes |
| Other Study ID Numbers: | 1383.00, NCI-2012-00670, P01CA078902 |
| Study First Received: | November 1, 1999 |
| Last Updated: | June 7, 2012 |
| Health Authority: | United States: Federal Government |
Additional relevant MeSH terms:
|
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Cyclosporins |
Cyclosporine Mycophenolic Acid Melphalan Mycophenolate mofetil Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antifungal Agents Anti-Infective Agents Therapeutic Uses Dermatologic Agents Antirheumatic Agents |
ClinicalTrials.gov processed this record on May 23, 2013