Stem Cell Transplantation in Treating Patients With Previously-Treated Multiple Myeloma - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00054353

Purpose

RATIONALE: Stem cell transplantation may be able to replace immune cells that were destroyed by previous cancer treatment. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Cyclosporine and mycophenolate mofetil may prevent this from happening.

PURPOSE: This phase I/II trial is studying donor stem cell transplantation to see how well it works in treating patients with multiple myeloma that has been previously treated.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: therapeutic allogeneic lymphocytes Drug: cyclosporine Drug: fludarabine phosphate Drug: melphalan Drug: mycophenolate mofetil Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Reduced-Intensity Allogeneic HSC Transplantation From HLA-Matched Related and Unrelated Donors for Patients With Multiple Myeloma

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Mycophenolate mofetil hydrochloride Mycophenolate Mofetil Melphalan Sarcolysin Melphalan hydrochloride

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Progression-free survival at 1 year [ Designated as safety issue: No ]
Treatment-related mortality at 100 days [ Designated as safety issue: No ]
Acute graft-versus-host disease grades III-IV [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	October 2002
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the efficacy of allogeneic hematopoietic stem cell transplantation, in terms of 1-year progression-free survival and overall survival, in patients with previously treated multiple myeloma.
Determine non-relapse mortality at day 100 in patients treated with this regimen.
Determine the incidence of grade II-IV acute graft-versus-host disease (GVHD) and chronic extensive GVHD in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive fludarabine IV over 30 minutes on days -5 to -3 and melphalan IV over 15-20 minutes on day -2. Patients undergo total body irradiation and allogeneic hematopoietic stem cell transplantation on day 0.

Patients also receive graft-versus-host disease prophylaxis according to the type of donor.

Related donor: Patients receive oral cyclosporine every 12 hours on days -3 to 80 followed by a taper until day 180 and oral mycophenolate mofetil every 12 hours on days 0-27.
Unrelated donor: Patients receive oral cyclosporine every 12 hours on days -3 to 100 followed by a taper until day 177 and oral mycophenolate mofetil every 8 hours on days 0-40 followed by a taper until day 96.

Patients are followed at days 28, 56, and 84; at months 6, 12, 18, and 24; and then annually for 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of multiple myeloma, meeting 1 of the following criteria:
- Progressive disease after at least 1 prior syngeneic or autologous hematopoietic stem cell transplantation (indicated by greater than 25% increase in serum or urine paraprotein levels or appearance of new lytic bone lesions or plasmacytomas)
- Unable to collect autologous peripheral blood stem cells due to poor marrow reserve OR contraindications to undergoing stem cell mobilization and has progressive disease after at least 4 prior courses of standard chemotherapy (e.g., dexamethasone/doxorubicin/vincristine)
Availability of 1 of the following donors:
- HLA genotypically matched identical sibling
- HLA phenotypically matched relative
- HLA phenotypically matched unrelated donor
  - Matched for serologically recognized HLA-A or B or C antigens and at least 5/6 HLA-A or B or C alleles
  - Matched for HLA-DRB1 and DQB1 alleles
- No identical twins

PATIENT CHARACTERISTICS:

Age

18 to 70

Performance status

Karnofsky 60-100%

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

No chronic viral hepatitis with bilirubin > 3 mg/dL
No biliary obstruction
No symptomatic biliary disease
No ascites related to portal hypertension
No bridging fibrosis
No bacterial or fungal liver abcess
No fulminant liver failure
No cirrhosis of liver with evidence of portal hypertension
Bilirubin no greater than 2 times upper limit of normal (ULN)
No uncorrectable hepatic synthetic dysfunction evidenced by prolonged PT
SGPT and SGOT no greater than 4 times ULN
No alcoholic hepatitis
No hepatic encephalopathy

Renal

Creatinine clearance at least 40 mL/min

Cardiovascular

LVEF at least 40%
No symptomatic heart failure
No poorly controlled hypertension

Pulmonary

DLCO at least 50%
No requirement for continuous supplemental oxygen

Other

Not pregnant or nursing
Fertile patients must use effective contraception during and for 12 months after study participation
HIV negative
Cytomegalovirus (CMV)-antigenemia negative
No impaired capacity that would preclude informed consent
No persistent mucositis or gastrointestinal symptoms requiring hyperalimentation and/or IV hydration
No prior or concurrent esophageal varices
No nonhematologic malignancy within the past 5 years except nonmelanoma skin cancer currently in complete remission wtih ≤ 20% risk of recurrence
No active nonhematologic malignancy except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics

Chemotherapy

See Disease Characteristics

Endocrine therapy

No concurrent steroids for autologous or syngeneic graft-versus-host disease

Radiotherapy

No other concurrent radiotherapy

Surgery

Not specified

Other

Recovered from prior therapy
At least 2 weeks since prior ganciclovir or foscarnet for previous CMV reactivation/infection
No concurrent ganciclovir or foscarnet for previous CMV reactivation/infection
No concurrent IV antibiotics for active infections
No concurrent bisphosphonates during and for 30 days after transplantation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00054353

Locations

United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
Italy
Universita di Torino
Turin, Italy, 10126

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Marco B. Mielcarek, MD

Fred Hutchinson Cancer Research Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Fred Hutchinson Cancer Research Center ( Marco B. Mielcarek )
Study ID Numbers:	CDR0000270417, FHCRC-1743.00
Study First Received:	February 5, 2003
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00054353 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Melphalan
Vidarabine
Antimetabolites, Antineoplastic
Cyclosporine
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Mycophenolic Acid
Paraproteinemias
Antibiotics, Antineoplastic
Hemostatic Disorders

Cyclosporins
Hemorrhagic Disorders
Therapeutic Uses
Antifungal Agents
Mycophenolate mofetil
Cardiovascular Diseases
Alkylating Agents
Dermatologic Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Hematologic Diseases
Vascular Diseases
Enzyme Inhibitors
Fludarabine monophosphate

ClinicalTrials.gov processed this record on November 09, 2009