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

• Register: ClinicalTrials.gov
• Last refreshed on: 28 January 2013
• Main ID: NCT00054353
• Date of registration: 05/02/2003
• Primary sponsor: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
• Public title: Reduced-Intensity Conditioning Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Multiple Myeloma
• Scientific title: Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation From HLA-Matched Related and Unrelated Donors for Patients With Multiple Myeloma - A Multi-Center Trial
• Date of first enrolment: October 2002
• Target sample size: 30
• Recruitment status: Active, not recruiting
• URL: http://clinicaltrials.gov/show/NCT00054353
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

Italy, United States

Contacts

• Name: Marco Mielcarek
• Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: 70 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Refractory Multiple Myeloma

Intervention(s)

Drug: cyclosporine

Drug: fludarabine phosphate

Drug: melphalan

Drug: mycophenolate mofetil

Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation

Procedure: peripheral blood stem cell transplantation

Radiation: total-body irradiation

Primary Outcome(s)

Incidences of acute GVHD (grades III-IV) and chronic (extensive) GVHD [Time Frame: Up to 5 years]

Non-relapse mortality [Time Frame: At day 100]

PFS [Time Frame: At 1 year post-transplant]

Secondary Outcome(s)

Engraftment [Time Frame: Up to 5 years]

OS [Time Frame: At 1 year post-transplant]

Relapse rate [Time Frame: Up to 5 years]

Response rate [Time Frame: Up to 5 years]

Secondary ID(s)

1743.00

NCI-2011-00386

P01CA078902

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)