Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer, Metastatic Kidney Cancer, or Aplastic Anemia

Sponsor

University of California, San Francisco (Other)

Overall Status

Unknown status

CT.gov ID

NCT00295997

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

17.5

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant using stem cells that closely match the patient's stem cells, 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 antithymocyte globulin before transplant and cyclosporine and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well a donor stem cell transplant works in treating patients with hematologic cancer, metastatic kidney cancer, or aplastic anemia.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Kidney Cancer Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms	Biological: anti-thymocyte globulin Biological: filgrastim Biological: graft-versus-tumor induction therapy Biological: therapeutic allogeneic lymphocytes Drug: busulfan Drug: cyclophosphamide Drug: fludarabine phosphate Drug: methotrexate Drug: mycophenolate mofetil Drug: tacrolimus Procedure: allogeneic bone marrow transplantation Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation	N/A

Detailed Description

OBJECTIVES:

Primary

Determine the treatment-related mortality (TRM) rate at 100 days in patients with hematologic malignancy, metastatic renal cell carcinoma, or aplastic anemia undergoing nonmyeloablative allogeneic stem cell transplantation using matched unrelated donors.

Secondary

Determine the TRM at 12 months in patients treated with this regimen.
Determine the 6-month engraftment rate in patients treated with this regimen.
Determine 1-year overall survival of patients treated with this regimen.

OUTLINE:

Nonmyeloablative preparative regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3, busulfan* IV over 6 hours on days -4 and -3, and anti-thymocyte globulin IV over 6-10 hours on days -4 to -1.

NOTE: *Patients with aplastic anemia receive cyclophosphamide IV over 2 hours on days -6 to -3 instead of busulfan.

Allogeneic stem cell reinfusion: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.
Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus orally twice daily or IV continuously beginning on day -2 and continuing for approximately for 6-12 months after transplantation. Patients also receive mycophenolate mofetil orally or IV twice daily on days 0 to 60 and methotrexate IV on days 1, 3, 6, and 11**.

NOTE: **Patients with aplastic anemia receive methotrexate IV on days 1, 3, and 6 (not day 11).

Donor lymphocyte infusion (DLI): After day 180, patients with no evidence of active GVHD may receive DLI. A second DLI may be infused > 8 weeks after the first in the absence of disease response or GVHD.

After completion of study treatment, patients are followed periodically for at least 2 years.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Non-myeloablative Allogeneic Stem Cell Transplantation With Match Unrelated Donors for Treatment of Hematologic Malignancies and Renal Cell Carcinoma and Aplastic Anemia

Study Start Date :

May 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
Aplastic anemia not responsive to immunosuppressive therapy
Metastatic renal cell carcinoma
Hematologic malignancy, including any of the following:
Acute myeloid leukemia (AML)* not curable with chemotherapy and meeting any of the following criteria:
AML with high-risk cytogenetic abnormalities (e.g., -7, -7q, -5, -5q, complex, Philadelphia chromosome-positive [Ph+])
AML evolved from prior myelodysplasia
AML secondary to prior chemotherapy
Failed to achieve remission
In second or subsequent remission NOTE: *Marrow blasts < 10%- can be achieved by chemotherapy
Myelodysplasia* with any of the following high-risk features:
Adverse cytogenetics (-7, 7q, -5, -5q, complex)
Excess blasts
Prior conversion to AML
Severe cytopenias with absolute neutrophil count < 500/mm^{3 or platelet
count < 20,000/mm}3 NOTE: *Marrow blasts < 10%- can be achieved by chemotherapy
Acute lymphoblastic leukemia (ALL)* not curable with chemotherapy and meeting any of the following criteria:
High-risk cytogenetics (Ph+, 11q23 abnormalities, monosomy 7)
More than 1 induction course required to achieve remission
Failed to enter remission
In second or subsequent remission NOTE: *Marrow blasts < 10 %
Chronic lymphocytic leukemia (CLL) with high-risk features, including any of the following:
Refractory to initial or subsequent therapy
Progression after initial response to therapy
Prolymphocytic morphology
Follicular lymphoma with any of the following high-risk features:
Refractory to initial or subsequent therapy
Progression after response to initial therapy
Has ≥ 3 International Prognostic Index (IPI) risk factors
Multiple myeloma
Stage II-III disease confirmed at diagnosis or after initial progression
Other lymphoma that has failed to respond to primary therapy, progressed, or recurred after prior therapy, including any of the following:
Diffuse large cell lymphoma
Mantle cell lymphoma
Hodgkin's lymphoma
Myeloproliferative disease with evidence of disease acceleration, including any of the following:
Myelofibrosis
Polycythemia vera
Essential thrombocythemia
Chronic myeloid leukemia (CML) that failed to be controlled by imatinib mesylate
Disease must be stable or responding to therapy
No rapid progression of malignant disease
Expected time to disease progression > 12 weeks
Not eligible for autologous stem cell transplantation
Matched unrelated donor available
9/10 HLA matched, including HLA-A, -B, -C, -DR, and -DQ

PATIENT CHARACTERISTICS:

Creatinine < 2.0 mg/dL
Creatinine clearance > 40 mL/min
Bilirubin < 3 mg/dL
Elevated total bilirubin due to Gilbert's disease allowed if direct bilirubin is normal
AST < 4 times upper limit of normal
Hepatitis C or B allowed provided bilirubin and AST are normal
Cardiac ejection fraction > 30%
DLCO > 40% of predicted
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No uncontrolled active infection requiring ongoing antibiotic treatment
No poor performance status
No poor organ function

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Prior stem cell or bone marrow transplantation allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
2	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096