Non-Myeloablative Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Treatment of Hematologic Malignancies, Renal Cell Carcinoma, and Aplastic Anemia

Sponsor

University of California, San Francisco (Other)

Overall Status

Completed

CT.gov ID

NCT00513175

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to examine transplant related mortality (TRM) at 100 days <30%. A TRM of >50% is considered unacceptable. This study also seeks a TRM at 12 months that is <50%, engraftment >90% (defined as donor cells >80% at 6 months), and 1 year overall survival >50%.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Myelodysplasia Acute Lymphoblastic Leukemia Chronic Lymphocytic Leukemia Follicular Lymphoma Multiple Myeloma NHL Myeloproliferative Diseases Chronic Myeloid Leukemia Renal Cell Carcinoma Aplastic Anemia

Study Design

Study Type:

Observational

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Non-Myeloablative Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Treatment of Hematologic Malignancies, Renal Cell Carcinoma, and Aplastic Anemia

Study Start Date :

Oct 1, 2001

Actual Study Completion Date :

Nov 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

<75 years old
Availability of suitable matched unrelated donor. We will require HLA matching at 9 of 10 loci including HLA A, B, C, DR and DQ. For patients treated at UCSF, typing will be done in the UCSF Immunogenetics Department. Typing will be done by high-resolution techniques at the allele level. Donors will be recruited through the National Marrow Donor Program (NMDP). Donors must meet the standards of NMDP as well as Institutional standards for donors at the center for which they are being collected.
Disease must be stable or responding to therapy. The expected time to disease progression should be greater than 12 weeks.
Disease types include:
Acute myeloid leukemia not expected to be curable with chemotherapy. This will include patients with high-risk cytogenetics (-7, -7q, -5, -5q, complex, Ph+), evolution from prior myelodysplasia or AML secondary to prior chemotherapy, failure to achieve remission, or second or subsequent remission. To ensure adequate time until disease progression, marrow blasts must be <10%. This may be achieved using chemotherapy treatment.
Myelodysplasia with high-risk features. These will include adverse cytogenetics (-7, -7q, -5, -5q, complex), excess blasts, prior conversion to AML, or severe cytopenias, with ANC<500uL or platelets <20,000uL. Marrow blasts must be <10%. This may be achieved using chemotherapy.
Acute lymphoblastic leukemia not expected to be curable with chemotherapy. This will include patients with high-risk cytogenetics (Ph+, 11q23 abnormalities, and monosomy 7), patients requiring more than one induction course to achieve remission, as well as patients failing to enter remission or in second or subsequent remission. Marrow blasts must be <10%.
Chronic lymphocytic leukemia with high-risk features. This will include refractoriness to initial or subsequent therapy, progression after initial response to therapy, or prolymphocytic (PLL) morphology.
Follicular lymphoma with high-risk features. This will include refractoriness to initial or subsequent therapy, progression after response to initial therapy, or

or equal 3 IPI risk factors.

Multiple myeloma, stage II-III. Patients are eligible either at diagnosis or after initial progression.
Other lymphomas including diffuse large cell lymphoma, mantle cell lymphoma, or Hodgkin's disease which as failed to respond to primary therapy, progressed or recurred after prior therapy.
Myeloproliferative diseases (myelofibrosis, polycythemia vera essential thrombocytosis) with evidence of disease acceleration.
Chronic myeloid leukemia with failure disease control by Imatinib.
Renal cell carcinoma with metastatic disease
Aplastic anemia not responsive to immunosuppressive therapy
Laboratory requirements (within 2 weeks of entry, EF and DLCO within 4 weeks): --Creatinine ,2.0mg/dL and creatinine clearance >40 mL/min
Bilirubin <3mg/dL, AST <4x upper limit of normal. Patients with elevated total bilirubin who are suspected of having Gilbert's Disease will be eligible if the direct bilirubin is normal.
Patients with hepatitis C and hepatitis B are eligible if bilirubin and AST meet above criteria
Cardiac ejection fraction >30%
DLCO >40% predicted
Negative pregnancy test (for females of reproductive age)
Absence of uncontrolled active infection.
Prior stem cell (or bone marrow) transplantation is permitted
Signed informed consent

Exclusion Criteria:

Active infection requiring ongoing antibiotic treatment
Poor performance status
Rapid progression of malignant disease
Opinion of BMT Committee that autologous transplant would be a preferable form of treatment
Organ function below requirements
Pregnancy