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

NCT ID: NCT00003954

Last Updated: 2020-02-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-03-31

Brief Summary

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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

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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.

Conditions

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Refractory Multiple Myeloma Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

melphalan

Intervention Type DRUG

Given IV

autologous hematopoietic stem cell transplantation

Intervention Type PROCEDURE

Undergo autologous bone marrow or PBSCT

autologous bone marrow transplantation

Intervention Type PROCEDURE

Undergo autologous bone marrow or PBSCT

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Undergo autologous bone marrow or PBSCT

total-body irradiation

Intervention Type RADIATION

Undergo TBI

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Undergo donor PBSCT

cyclosporine

Intervention Type DRUG

Given IV and PO

mycophenolate mofetil

Intervention Type DRUG

Given PO

therapeutic allogeneic lymphocytes

Intervention Type BIOLOGICAL

Undergo DLI

Interventions

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melphalan

Given IV

Intervention Type DRUG

autologous hematopoietic stem cell transplantation

Undergo autologous bone marrow or PBSCT

Intervention Type PROCEDURE

autologous bone marrow transplantation

Undergo autologous bone marrow or PBSCT

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Undergo autologous bone marrow or PBSCT

Intervention Type PROCEDURE

total-body irradiation

Undergo TBI

Intervention Type RADIATION

peripheral blood stem cell transplantation

Undergo donor PBSCT

Intervention Type PROCEDURE

cyclosporine

Given IV and PO

Intervention Type DRUG

mycophenolate mofetil

Given PO

Intervention Type DRUG

therapeutic allogeneic lymphocytes

Undergo DLI

Intervention Type BIOLOGICAL

Other Intervention Names

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Alkeran CB-3025 L-PAM L-phenylalanine mustard L-Sarcolysin ABMT bone marrow transplantation, autologous transplantation, autologous bone marrow PBPC transplantation PBSC transplantation peripheral blood progenitor cell transplantation transplantation, peripheral blood stem cell TBI PBPC transplantation PBSC transplantation peripheral blood progenitor cell transplantation transplantation, peripheral blood stem cell ciclosporin cyclosporin cyclosporin A CYSP Sandimmune Cellcept MMF ALLOLYMPH

Eligibility Criteria

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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
Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Maloney

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

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City of Hope

Duarte, California, United States

Site Status

University of Colorado

Denver, Colorado, United States

Site Status

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

University of Torino

Torino, , Italy

Site Status

Countries

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United States Italy

References

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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.

Reference Type DERIVED
PMID: 32499241 (View on PubMed)

Other Identifiers

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NCI-2012-00670

Identifier Type: REGISTRY

Identifier Source: secondary_id

P01CA078902

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1383.00

Identifier Type: -

Identifier Source: org_study_id

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