Melphalan and Stem Cell Transplant Before Total-Body Irradiation and Donor Stem Cell Transplant in Treating Patients With Stage I-III Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00003954
First received: November 1, 1999
Last updated: May 22, 2014
Last verified: May 2014
  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

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
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:
  • ABMT
  • bone marrow transplantation, autologous
  • transplantation, autologous bone marrow
Procedure: peripheral blood stem cell transplantation
Undergo autologous bone marrow or PBSCT
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Procedure: peripheral blood stem cell transplantation
Undergo donor PBSCT
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Drug: cyclosporine
Given IV and PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: mycophenolate mofetil
Given PO
Other Names:
  • Cellcept
  • MMF
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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003954

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
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: David Maloney Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
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: May 22, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Cyclosporine
Cyclosporins
Melphalan
Mycophenolate mofetil
Mycophenolic Acid
Alkylating Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 21, 2014