Multiple Myeloma Clinical Trial
NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders
Summary
RATIONALE: Giving low doses of chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving immunosuppressive therapy before or after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well chemotherapy followed by donor peripheral stem cell transplant works in treating patients with hematologic cancer or aplastic anemia.
Full Description
OBJECTIVES:
Determine the safety and toxic effects of nonmyeloablative allogeneic peripheral blood stem cell transplantation in patients with a hematologic malignancy or aplastic anemia.
Determine clinical response and overall outcome of patients treated with this regimen.
Determine the incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism in patients treated with this regimen.
OUTLINE:
Preparative regimen:
Matched related and unrelated donor transplantation:
Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine IV over 30 minutes on days -5 to -1.
Cord blood transplantation:
Patients receive the same regimen as above plus anti-thymocyte globulin IV over 4 hours on days -3 to -1.
Graft-vs-host disease (GVHD) prophylaxis:
Matched related and unrelated donor transplantation:
Patients receive oral tacrolimus (or IV) once daily and oral mycophenolate mofetil (MMF) (or IV) twice daily on days -1 to 60 followed by tapering* of this regimen. Patients then receive methotrexate IV on days 1, 3, and 6.
Cord blood transplantation:
Patients receive tacrolimus and MMF in the same regimen as above plus methylprednisolone twice daily on days 1-19 or until blood counts recover.
Allogeneic stem cell reinfusion: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0. Patients then receive sargramostim (GM-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.
Donor lymphocyte infusion (DLI): Patients not converting to 100% donor T-cell chimerism by day 120 and showing signs of progresson of disease after tacrolimus and MMF withdrawal may receive DLI every 8 weeks for up to 3 infusions. Cord blood recipients do not receive DLI.
Patients are followed at day 100-120, every 3 months for 2 years, and then every 6 months for 5 years.
PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 6-7 years.
Eligibility Criteria
DISEASE CHARACTERISTICS:
Diagnosis of aplastic anemia
Severe disease
Failed at least 1 course of standard immunosuppressive regimen with cyclosporine and anti-thymocyte globulin OR
Histologically confirmed hematologic malignancy including the following:
Acute leukemia
Any of the following types:
Acute myeloid leukemia (AML) with antecedent myelodysplastic syndromes
Secondary AML
AML with high-risk cytogenetic abnormalities
Acute lymphoblastic leukemia with high-risk cytogenetic abnormalities
Resistant or recurrent disease after combination chemotherapy with at least 1 standard regimen OR
In first remission at high risk of relapse
Chronic myelogenous leukemia
Chronic phase meeting at least 1 of the following criteria:
Failed imatinib mesylate
Failed interferon after at least 6 months of treatment with minimum of 21 million units of interferon per week
Unable to tolerate interferon
Accelerated phase (blasts less than 20%)
Myeloproliferative and myelodysplastic syndromes
Myelofibrosis (after splenectomy)
Refractory anemia
Refractory anemia with excess blasts
Chronic myelomonocytic leukemia
Lymphoproliferative disease
Chronic lymphocytic leukemia
Symptomatic disease after first-line chemotherapy
Low-grade non-Hodgkin's lymphoma (recurrent or persistent)
Symptomatic disease after first-line chemotherapy
Multiple myeloma
Progressive disease after autologous stem cell transplantation
Waldenstrom's macroglobulinemia
Failed 1 standard regimen
Non-Hodgkin's lymphoma meeting the following criteria:
Intermediate or high grade
Controlled and chemosensitive disease
First remission lymphoblastic or small non-cleaved cell lymphoma at high risk of relapse
Hodgkin's lymphoma
Relapsed and chemosensitive disease
Not eligible for standard myeloablative allogeneic stem cell transplantation
Availability of any of the following donor types:
Related donor matched at 5 or 6 HLA antigens (A, B, DR)
Unrelated donor fully matched by molecular analysis at A, B, DRB1, and DQB1 loci
Single antigen mismatch at C allowed
Cord blood that is 4, 5, or 6 match with recipient HLA antigens (A, B, DR) NOTE: No syngeneic donors permitted
No uncontrolled CNS disease (for hematologic malignancies) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
Age
4 to 75 (if related or unrelated donor peripheral blood or marrow transplantation)
4 to 60 (if unrelated cord blood transplantation)
Performance status
Karnofsky > 50%
Life expectancy
Not specified
Hematopoietic
Not specified
Hepatic
Bilirubin less than 3 times normal
Alkaline phosphatase less than 3 times normal
AST/ALT less than 3 times normal
No Child's class B or C liver failure
Renal
Creatinine clearance greater than 40 mL/min
Cardiovascular
Cardiac ventricular ejection fraction at least 35% by MUGA
No cardiovascular disease
Pulmonary
DLCO at least 40% of predicted, corrected for hemoglobin and/or alveolar ventilation
Other
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV antibody negative
No uncontrolled diabetes mellitus
No active serious infection
No other disease that would preclude study therapy
No other concurrent malignancy except non-melanoma skin cancer
No concurrent serious psychiatric illness
PRIOR CONCURRENT THERAPY:
Biologic therapy
See Disease Characteristics
patients may have received a prior autologous blood or marrow transplantation (BMT)
At least 6 months since prior allogeneic BMT
Chemotherapy
See Disease Characteristics
At least 2 weeks since prior chemotherapy, radiation or surgery
Endocrine therapy
Not specified
Radiotherapy
At least 2 weeks since prior radiotherapy
Surgery
At least 2 weeks since prior surgery
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There is 1 Location for this study
Buffalo New York, 14263, United States
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