Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00014508

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy. Sometimes the transplanted cells are rejected by the body's tissues. Peripheral stem cell transplantation with the person's own stem cells followed by donor peripheral stem cell transplantation may prevent this from happening.

PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy with autologous peripheral stem cell transplantation and donor peripheral stem cell transplantation in treating patients who have multiple myeloma.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: sargramostim Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: melphalan Procedure: peripheral blood stem cell transplantation	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Trial Of Autologous Stem Cell Transplant Followed By Mini-Allogeneic Stem Cell Transplant In Lieu Of Standard Allogeneic Bone Marrow Transplantation For Treatment Of Multiple Myeloma

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Cyclophosphamide Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Sargramostim Melphalan Sarcolysin Melphalan hydrochloride

U.S. FDA Resources

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

Study Start Date:	April 2001
Primary Completion Date:	February 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the incidence of early mortality in patients with multiple myeloma treated with melphalan and autologous peripheral blood stem cell (PBSC) transplantation followed by fludarabine, cyclophosphamide, and allogeneic PBSC transplantation.
Determine the incidence of early allogeneic graft failure (before day 100 after allogeneic PBSC transplantation) and the incidence of severe acute graft-versus-host disease (GVHD) in patients treated with this regimen.
Determine the toxicity of this regimen in these patients.
Determine the overall and disease-free survival of patients treated with this regimen.
Correlate changes in the T-cell population with clinical outcome, such as survival, in patients treated with this regimen.
Correlate changes in the T-cell population with the incidence of GVHD, use of immunosuppressive agents, and effects of fludarabine in patients treated with this regimen.
Determine the degree of chimerism after allogeneic PBSC transplantation and the time course over which it is established in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive melphalan IV over 15 minutes on day -1. Autologous peripheral blood stem cells (PBSCs) are reinfused on day 0. Patients also receive sargramostim (GM-CSF) subcutaneously (SC) or IV over at least 30 minutes daily beginning on day 1 and continuing until blood counts recover. Beginning 100-182 days after autologous PBSC transplantation, patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -3 and -2. Allogeneic PBSCs are infused on day 0. Patients may receive a second allogeneic PBSC infusion on day 1. Patients also receive GM-CSF SC or IV over at least 30 minutes daily beginning on day 1 and continuing until blood counts recover. Cyclosporine is administered IV or orally twice daily as graft-versus-host disease (GVHD) prophylaxis, beginning on day -1 and continuing until day 60, followed by a taper in the absence of GVHD.

Patients are followed for 5 years.

PROJECTED ACCRUAL: A total 19-46 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:
- Bone marrow plasmacytosis with at least 10% plasma cells
- Sheets of plasma cells
- Biopsy-proven plasmacytoma
Meets at least 1 of the following criteria:
- Presence of myeloma (M)-protein in the serum
- Presence of M-protein in the urine
- Radiographic evidence of osteolytic lesions
  - Generalized osteoporosis allowed if at least 20% plasma cells in bone marrow
No non-secretory myeloma
- Prior M-protein in serum or urine allowed provided patient is now in complete remission
Must be receiving conventional-dose chemotherapy as initial therapy or as salvage therapy
Must have HLA-A, -B, and -DR genotypically identical sibling donor

PATIENT CHARACTERISTICS:

Age:

18 to 70

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics

Hepatic:

AST no greater than 3 times upper limit of normal
Bilirubin less than 2.0 mg/dL

Renal:

Not specified

Cardiovascular:

LVEF greater than 40% at rest if symptomatic cardiac disease is present

Pulmonary:

DLCO greater than 50% of predicted (corrected for hemoglobin) if symptomatic pulmonary disease is present

Other:

Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior autologous or allogeneic peripheral blood stem cell or bone marrow transplantation

Chemotherapy:

See Disease Characteristics
More than 28 days since prior chemotherapy (including primary chemotherapy for hematopoietic stem cell collection)
No other concurrent cytotoxic chemotherapy between autologous and allogeneic transplantation

Endocrine therapy:

Prior dexamethasone or other corticosteroids allowed
Concurrent corticosteroids between autologous and allogeneic transplantation allowed

Radiotherapy:

Concurrent radiotherapy between autologous and allogeneic transplantation allowed

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00014508

Locations

United States, Florida
Baptist Cancer Institute - Jacksonville
Jacksonville, Florida, United States, 32207-8554
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Cancer Center at Tufts - New England Medical Center
Boston, Massachusetts, United States, 02111
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, New Jersey
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
CCOP - Northern New Jersey
Hackensack, New Jersey, United States, 07601
United States, New York
MBCCOP-Our Lady of Mercy Cancer Center
Bronx, New York, United States, 10466
United States, Ohio
Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
Cleveland, Ohio, United States, 44106-5065
MetroHealth's Cancer Care Center at MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
United States, Pennsylvania
Abramson Cancer Center at the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Neal Flomenberg, MD

Kimmel Cancer Center (KCC)

More Information

Additional Information:

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

Publications:

Vesole DH, Zhang L, Flomenberg N, et al.: A phase II trial of autologous stem cell transplant (AHSCT) followed by mini-allogeneic stem cell transplant (AlloTx) for the treatment of multiple myeloma: analysis of ECOG E4A98. [Abstract] Blood 110 (11): A-3027, 2007.

Vesole DH, Zhang L, Flomenberg N, Greipp PR, Lazarus HM; ECOG Myeloma and BMT Committees. A Phase II trial of autologous stem cell transplantation followed by mini-allogeneic stem cell transplantation for the treatment of multiple myeloma: an analysis of Eastern Cooperative Oncology Group ECOG E4A98 and E1A97. Biol Blood Marrow Transplant. 2009 Jan;15(1):83-91.

Study ID Numbers:	CDR0000068551, ECOG-E4A98
Study First Received:	April 10, 2001
Last Updated:	February 25, 2009
ClinicalTrials.gov Identifier:	NCT00014508 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

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

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

ClinicalTrials.gov processed this record on November 27, 2009