Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma

Sponsor

Eastern Cooperative Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00014508

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

121.8

Actual Duration (Months)

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	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 2

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 1, 2001

Actual Primary Completion Date :

Feb 1, 2007

Actual Study Completion Date :

May 27, 2011

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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