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Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation From HLA-Matched Related and Unrelated Donors for Patients With Multiple Myeloma - A Multi-Center Trial

Phase 1/Phase 2
18 Years
70 Years
Open (Enrolling)
Refractory Multiple Myeloma

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Trial Information

Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation From HLA-Matched Related and Unrelated Donors for Patients With Multiple Myeloma - A Multi-Center Trial


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.


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 177
(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.

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Description:

PFS will be calculated for all patients from the date of transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission.

Outcome Time Frame:

At 1 year post-transplant

Safety Issue:


Principal Investigator

Marco Mielcarek

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

October 2002

Completion Date:

Related Keywords:

  • Refractory Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109