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

Primary Purpose

Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
melphalan
autologous hematopoietic stem cell transplantation
autologous bone marrow transplantation
peripheral blood stem cell transplantation
total-body irradiation
peripheral blood stem cell transplantation
cyclosporine
mycophenolate mofetil
therapeutic allogeneic lymphocytes
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Multiple Myeloma

Eligibility Criteria

undefined - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope
  • University of Colorado
  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  • University of Torino

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)

Arm Description

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.

Outcomes

Primary Outcome Measures

PFS
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
Establish stable allogeneic engraftment (mixed or full donor chimerism)

Secondary Outcome Measures

Overall survival
Estimated by the method of Kaplan and Meier. Confidence intervals will be estimated.
Relapse rate
Summarized using cumulative incidence estimates. Confidence intervals will be estimated.
Response rate
Confidence intervals will be estimated.
Ability to convert mixed to full donor chimerism with DLI
Confidence intervals will be estimated.

Full Information

First Posted
November 1, 1999
Last Updated
February 4, 2020
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003954
Brief Title
Melphalan and Stem Cell Transplant Before Total-Body Irradiation and Donor Stem Cell Transplant in Treating Patients With Stage I-III Multiple Myeloma
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
March 1999 (undefined)
Primary Completion Date
December 2002 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (Melphalan and PBSCT before TBI and Donor PBSCT)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
melphalan
Other Intervention Name(s)
Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
autologous hematopoietic stem cell transplantation
Intervention Description
Undergo autologous bone marrow or PBSCT
Intervention Type
Procedure
Intervention Name(s)
autologous bone marrow transplantation
Other Intervention Name(s)
ABMT, bone marrow transplantation, autologous, transplantation, autologous bone marrow
Intervention Description
Undergo autologous bone marrow or PBSCT
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Other Intervention Name(s)
PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Intervention Description
Undergo autologous bone marrow or PBSCT
Intervention Type
Radiation
Intervention Name(s)
total-body irradiation
Other Intervention Name(s)
TBI
Intervention Description
Undergo TBI
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Other Intervention Name(s)
PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Intervention Description
Undergo donor PBSCT
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Other Intervention Name(s)
ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune
Intervention Description
Given IV and PO
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Other Intervention Name(s)
Cellcept, MMF
Intervention Description
Given PO
Intervention Type
Biological
Intervention Name(s)
therapeutic allogeneic lymphocytes
Other Intervention Name(s)
ALLOLYMPH
Intervention Description
Undergo DLI
Primary Outcome Measure Information:
Title
PFS
Description
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.
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
Title
Decrease in the short-term transplant-related mortality
Time Frame
Day 100 after allograft
Title
Establish stable allogeneic engraftment (mixed or full donor chimerism)
Time Frame
At day 56 after allografting
Secondary Outcome Measure Information:
Title
Overall survival
Description
Estimated by the method of Kaplan and Meier. Confidence intervals will be estimated.
Time Frame
Up to 3 years
Title
Relapse rate
Description
Summarized using cumulative incidence estimates. Confidence intervals will be estimated.
Time Frame
Up to 3 years
Title
Response rate
Description
Confidence intervals will be estimated.
Time Frame
Up to 3 years
Title
Ability to convert mixed to full donor chimerism with DLI
Description
Confidence intervals will be estimated.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Maloney
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of Colorado
City
Denver
State/Province
Colorado
ZIP/Postal Code
80217
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
University of Torino
City
Torino
ZIP/Postal Code
10126
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
32499241
Citation
Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.
Results Reference
derived

Learn more about this trial

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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