Reduced-Intensity Conditioning Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Multiple Myeloma

NCT ID: NCT00054353

Last Updated: 2017-10-16

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-10-31

Study Completion Date

2012-10-14

Brief Summary

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This phase I/II trial studies the side effects of giving reduced-intensity conditioning followed by donor peripheral blood stem cell transplant (PBSCT) and how well it works in treating patients with multiple myeloma (MM). Giving low doses of chemotherapy, such as fludarabine phosphate and melphalan, and total-body irradiation (TBI) before a donor PBSCT helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine after transplant may stop this from happening.

Detailed Description

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PRIMARY OBJECTIVES:

I. To evaluate the efficacy of this approach by determining the 1-year progression-free survival (PFS) and overall survival (OS).

II. To evaluate day 100 non-relapse mortality.

III. To determine the incidences of grades II-IV acute graft-versus-host disease (GVHD) and chronic extensive GVHD.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -5 to -3 and intermediate-dose melphalan IV over 15-20 minutes on day -2. Patients also undergo low-dose TBI on day 0.

TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 80 with taper to day 180 (related donors) or on days -3 to 100 with taper to day 180 (unrelated donors). Patients also receive mycophenolate mofetil PO BID on days 0-27 (related donors) or thrice daily (TID) on days 0-40 with taper to day 96 (unrelated donors).

After completion of study treatment, patients are followed up at 3, 6, 12, 18, and 24 months, and then annually thereafter for 5 years.

Conditions

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Refractory Multiple Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Related Donor

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -3 and intermediate-dose melphalan IV over 15-20 minutes on day -2. Patients also undergo low-dose TBI on day 0.

TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 80 with taper to day 180 (related donors) or on days -3 to 100 with taper to day 180 (unrelated donors). Patients also receive mycophenolate mofetil PO BID on days 0-27 (related donors) or TID on days 0-40 with taper to day 96 (unrelated donors).

Group Type EXPERIMENTAL

fludarabine phosphate

Intervention Type DRUG

Given IV

melphalan

Intervention Type DRUG

Given IV

total-body irradiation

Intervention Type RADIATION

Undergo TBI

mycophenolate mofetil

Intervention Type DRUG

Given PO

cyclosporine

Intervention Type DRUG

Given PO

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

Undergo reduced-intensity allogeneic PBSCT

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Undergo reduced-intensity allogeneic PBSCT

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Unrelated Donor

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -3 and intermediate-dose melphalan IV over 15-20 minutes on day -2. Patients also undergo low-dose TBI on day 0.

TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 80 with taper to day 180 (related donors) or on days -3 to 100 with taper to day 180 (unrelated donors). Patients also receive mycophenolate mofetil PO BID on days 0-27 (related donors) or TID on days 0-40 with taper to day 96 (unrelated donors).

Group Type EXPERIMENTAL

fludarabine phosphate

Intervention Type DRUG

Given IV

melphalan

Intervention Type DRUG

Given IV

total-body irradiation

Intervention Type RADIATION

Undergo TBI

mycophenolate mofetil

Intervention Type DRUG

Given PO

cyclosporine

Intervention Type DRUG

Given PO

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

Undergo reduced-intensity allogeneic PBSCT

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Undergo reduced-intensity allogeneic PBSCT

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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fludarabine phosphate

Given IV

Intervention Type DRUG

melphalan

Given IV

Intervention Type DRUG

total-body irradiation

Undergo TBI

Intervention Type RADIATION

mycophenolate mofetil

Given PO

Intervention Type DRUG

cyclosporine

Given PO

Intervention Type DRUG

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Undergo reduced-intensity allogeneic PBSCT

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Undergo reduced-intensity allogeneic PBSCT

Intervention Type PROCEDURE

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

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2-F-ara-AMP Beneflur Fludara Alkeran CB-3025 L-PAM L-phenylalanine mustard L-Sarcolysin TBI Cellcept MMF ciclosporin cyclosporin cyclosporin A CYSP Sandimmune PBPC transplantation PBSC transplantation peripheral blood progenitor cell transplantation transplantation, peripheral blood stem cell

Eligibility Criteria

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Inclusion Criteria

* Meet Salmon and Durie criteria for initial diagnosis of MM; transplant will be offered to patients with previously treated MM who meet one of the following criteria:

* Patient received at least one prior autologous or syngeneic hematopoietic SCT (HSCT) and now has progressive disease (PD) (greater than 25% increase in serum or urine paraprotein levels compared to best response status after autograft or appearance of new lytic bone lesions or plasmocytomas)
* Patient is not able to collect autologous PBSC due to poor marrow reserve (insufficient HSC-mobilization: \< 2.5 x 10\^6 cluster of differentiation \[CD\]34+ cells/kg); or contraindications to undergoing HSC-mobilization; patient now has PD and has received at least 4 cycles of standard chemotherapy (e.g. vincristine sulfate, doxorubicin hydrochloride, and dexamethasone \[VAD\]) in the past
* Patients must have the capacity to give informed consent
* DONOR: Human leukocyte antigen (HLA) genotypically identical sibling or phenotypically matched relative
* DONOR: HLA phenotypically matched unrelated donor (according to Standard Practice HLA matching criteria)

* Matched for serologically recognized HLA-A or B or C antigens and at least five of six HLA-A or B or C alleles
* Matched for HLA DRB1 and DQB1 alleles (defined by high-resolution typing) at the allele level
* DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis for PBSC collection
* DONOR: Donor must have adequate veins for leukapheresis or agree to placement of a temporary central venous catheter

Exclusion Criteria

* Karnofsky score \< 60%
* Left ventricular ejection fraction \< 40% or symptomatic heart failure; ejection fraction is required if age \> 50 years or there is a history of anthracycline exposure or history of cardiac disease
* Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3 mg/dL,or symptomatic biliary disease
* Diffusion capacity of carbon monoxide (DLCO) \< 50% (corrected) or receiving continuous supplemental oxygen
* Creatinine clearance \< 40 mL/min
* Patients with poorly controlled hypertension
* Seropositive for the human immunodeficiency virus (HIV)
* Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a \> 20% risk of disease recurrence
* Pregnancy or breastfeeding
* Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
* Not fully recovered from previous high-dose therapy:

* Persistent mucositis and gastrointestinal symptoms requiring hyperalimentation and/or intravenous hydration
* On steroids for autologous/syngeneic GVHD
* On IV antibiotics for documented infections
* Cytomegalovirus (CMV)-antigenemia positive
* On ganciclovir or foscarnet for previous CMV reactivation/infection; off of this therapy for less than two weeks despite documented CMV-antigenemia- negativity (identification \[ID\] should be consulted if there is persistent CMV antigenemia post autograft)
* Ongoing radiotherapy
* Patients who meet any of these criteria may be discussed with the principal investigator for recommendations as to the timing of the allograft
* Patients with active bacterial or fungal infections unresponsive to medical therapy
* DONOR: Identical twin
* DONOR: Donors unwilling to donate PBSC
* DONOR: Pregnancy
* DONOR: Infection with 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
* DONOR: Age \< 12 years
* DONOR: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 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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Marco Mielcarek

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Marco Mielcarek

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

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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

Other Identifiers

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NCI-2011-00386

Identifier Type: REGISTRY

Identifier Source: secondary_id

1743.00

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1743.00

Identifier Type: -

Identifier Source: org_study_id