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

3 januari 2014 uppdaterad av: University of California, San Francisco

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

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.

Studieöversikt

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Förväntat)

35

Fas

  • Inte tillämpbar

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

    • California
      • San Francisco, California, Förenta staterna, 94115
        • UCSF Comprehensive Cancer Center
    • North Carolina
      • Winston-Salem, North Carolina, Förenta staterna, 27157-1096
        • Wake Forest University Comprehensive Cancer Center

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

Inte äldre än 74 år (Barn, Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Maskning: Ingen (Open Label)

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Utredare

  • Huvudutredare: Charles A. Linker, MD, University of California, San Francisco

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 maj 2005

Studieregistreringsdatum

Först inskickad

23 februari 2006

Först inskickad som uppfyllde QC-kriterierna

23 februari 2006

Första postat (Uppskatta)

24 februari 2006

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

6 januari 2014

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

3 januari 2014

Senast verifierad

1 april 2007

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • CDR0000463522
  • UCSF-01251
  • UCSF-H5010-19585-05
  • UCSF-2101

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