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

NCT00054353 | Completed Phase 1 Results DMC

• 3 other identifiers: 1743.00NCI-2011-00386P30CA015704
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (4)

• PFS

  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. Progressive disease is defined as greater than 25% increase in serum or urine M proteins compared to best response status after autologous transplant and/or appearance of new lytic bone lesions or plasmocytomas.

  At 1 year post-transplant

• Non-relapse Mortality

  Early NRM will be monitored in a sequential fashion.

  At day 100

• Incidence of Acute GVHD (Grades III-IV)

  Number of patients with Grade III-IV acute GVHD post-transplant. Severe GVHD will be monitored in a sequential fashion.

  Up to 5 years

• Incidence of Chronic (Extensive) GVHD

  Number of subjects with chronic extensive GVHD post-transplant. Severe GVHD will be monitored in a sequential fashion.

  Up to 5 years

Secondary Outcomes (4)

• OS

  At 6 months and then every year thereafter, up to 5 years

• Engraftment

  Up to 5 years

• Relapse Rate

  Up to 5 years

• Response Rate

  Up to 5 years

Study Arms (2)

Related Donor

EXPERIMENTAL

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).

Drug: fludarabine phosphate; Drug: melphalan; Radiation: total-body irradiation; Drug: mycophenolate mofetil; Drug: cyclosporine; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Other: laboratory biomarker analysis

Unrelated Donor

EXPERIMENTAL

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).

Drug: fludarabine phosphate; Drug: melphalan; Radiation: total-body irradiation; Drug: mycophenolate mofetil; Drug: cyclosporine; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Other: laboratory biomarker analysis

Interventions

fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Related Donor; Unrelated Donor

melphalan DRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin

Related Donor; Unrelated Donor

total-body irradiation RADIATION

Undergo TBI

Also known as: TBI

Related Donor; Unrelated Donor

mycophenolate mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Related Donor; Unrelated Donor

cyclosporine DRUG

Given PO

Also known as: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune

Related Donor; Unrelated Donor

nonmyeloablative allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo reduced-intensity allogeneic PBSCT

Related Donor; Unrelated Donor

peripheral blood stem cell transplantation PROCEDURE

Undergo reduced-intensity allogeneic PBSCT

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Related Donor; Unrelated Donor

laboratory biomarker analysis OTHER

Correlative studies

Related Donor; Unrelated Donor

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

University of Torino

Torino, 10126, Italy

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

fludarabine phosphate; Melphalan; Whole-Body Irradiation; Mycophenolic Acid; Cyclosporine; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Radiotherapy; Therapeutics; Investigative Techniques; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Marco Mielcarek, MD
• Organization: Fred Hutch

mmielcar@fredhutch.org

Study Officials

• Marco Mielcarek

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 5, 2003
• First Posted: February 6, 2003
• Study Start: October 1, 2002
• Primary Completion: October 1, 2009
• Study Completion: October 14, 2012
• Last Updated: October 16, 2017
• Results First Posted: October 16, 2017

Record last verified: 2017-09

Locations

US (1); IT (1)