- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00295997
Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer, Metastatic Kidney Cancer, or Aplastic Anemia
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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
- Medicin: cyclophosphamid
- Medicin: methotrexat
- Biologisk: anti-thymocyt globulin
- Biologisk: terapeutiske allogene lymfocytter
- Medicin: fludarabin fosfat
- Procedure: allogen knoglemarvstransplantation
- Medicin: busulfan
- Procedure: perifer blodstamcelletransplantation
- Biologisk: filgrastim
- Biologisk: graft-versus-tumor-induktionsterapi
- Medicin: tacrolimus
- Medicin: mycophenolatmofetil
- Procedure: ikke-myeloablativ allogen hæmatopoietisk stamcelletransplantation
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Forventet)
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiesteder
-
-
California
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San Francisco, California, Forenede Stater, 94115
- UCSF Comprehensive Cancer Center
-
-
North Carolina
-
Winston-Salem, North Carolina, Forenede Stater, 27157-1096
- Wake Forest University Comprehensive Cancer Center
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-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Maskning: Ingen (Åben etiket)
Samarbejdspartnere og efterforskere
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Charles A. Linker, MD, University of California, San Francisco
Datoer for undersøgelser
Studer store datoer
Studiestart
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
- stadium IV nyrecellekræft
- tilbagevendende nyrecellekræft
- primær myelofibrose
- stadium IV grad 3 follikulært lymfom
- tilbagevendende grad 3 follikulært lymfom
- tilbagevendende voksent diffust storcellet lymfom
- tilbagevendende voksen immunoblastisk storcellet lymfom
- tilbagevendende storcellet lymfom i barndommen
- kronisk myelomonocytisk leukæmi
- de novo myelodysplastiske syndromer
- tidligere behandlede myelodysplastiske syndromer
- sekundære myelodysplastiske syndromer
- akut myeloid leukæmi hos voksne med 11q23 (MLL) abnormiteter
- akut myeloid leukæmi hos voksne med inv(16)(p13;q22)
- akut myeloid leukæmi hos voksne med t(15;17)(q22;q12)
- akut myeloid leukæmi hos voksne med t(16;16)(p13;q22)
- sekundær akut myeloid leukæmi
- akut lymfatisk leukæmi i barndommen i remission
- akut myeloid leukæmi i barndommen i remission
- juvenil myelomonocytisk leukæmi
- kronisk fase kronisk myelogen leukæmi
- kronisk myelogen leukæmi i barndommen
- barndoms myelodysplastiske syndromer
- tilbagevendende akut myeloid leukæmi hos voksne
- akut myeloid leukæmi hos voksne i remission
- recidiverende voksen Hodgkin lymfom
- tilbagevendende/refraktær Hodgkin-lymfom i barndommen
- blastisk fase kronisk myelogen leukæmi
- recidiverende kronisk myelogen leukæmi
- stadium III grad 1 follikulært lymfom
- stadium III grad 2 follikulært lymfom
- stadium III grad 3 follikulært lymfom
- stadium IV grad 1 follikulært lymfom
- stadium IV grad 2 follikulært lymfom
- stadium II myelomatose
- stadium III myelomatose
- tilbagevendende grad 1 follikulært lymfom
- tilbagevendende grad 2 follikulært lymfom
- ikke-sammenhængende stadium II grad 1 follikulært lymfom
- ikke-sammenhængende stadium II grad 2 follikulært lymfom
- tilbagevendende lymfoblastisk lymfom hos voksne
- tilbagevendende kappecellelymfom
- refraktær kronisk lymfatisk leukæmi
- stadium III kronisk lymfatisk leukæmi
- stadium IV kronisk lymfatisk leukæmi
- refraktær myelomatose
- tilbagevendende akut lymfatisk leukæmi hos voksne
- polycytæmi vera
- essentiel trombocytæmi
- prolymfocytisk leukæmi
- tilbagevendende akut lymfatisk leukæmi hos børn
- ikke-sammenhængende stadium II grad 3 follikulært lymfom
- accelereret fase kronisk myelogen leukæmi
- akut lymfatisk leukæmi hos voksne i remission
- tilbagevendende akut myeloid leukæmi i barndommen
- myelodysplastisk/myeloproliferativ neoplasma, uklassificerbar
- kronisk eosinofil leukæmi
- kronisk neutrofil leukæmi
- atypisk kronisk myeloid leukæmi, BCR-ABL1 negativ
Yderligere relevante MeSH-vilkår
- Patologiske processer
- Hjerte-kar-sygdomme
- Karsygdomme
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Lymfoproliferative lidelser
- Lymfesygdomme
- Immunproliferative lidelser
- Urologiske neoplasmer
- Urogenitale neoplasmer
- Neoplasmer efter sted
- Nyresygdomme
- Urologiske sygdomme
- Adenocarcinom
- Karcinom
- Neoplasmer, kirtel og epitel
- Sygdom
- Knoglemarvssygdomme
- Hæmatologiske sygdomme
- Hæmoragiske lidelser
- Hæmostatiske lidelser
- Paraproteinæmier
- Blodproteinforstyrrelser
- Anæmi
- Forstadier til kræft
- Knoglemarvssvigtsforstyrrelser
- Neoplasmer
- Lymfom
- Nyre-neoplasmer
- Karcinom, nyrecelle
- Syndrom
- Myelodysplastiske syndromer
- Myelomatose
- Neoplasmer, Plasmacelle
- Leukæmi
- Præleukæmi
- Plasmacytom
- Myeloproliferative lidelser
- Myelodysplastisk-myeloproliferative sygdomme
- Anæmi, aplastisk
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Anti-infektionsmidler
- Nukleinsyresyntesehæmmere
- Enzymhæmmere
- Antirheumatiske midler
- Antimetabolitter, Antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Antineoplastiske midler, Alkylering
- Alkyleringsmidler
- Myeloablative agonister
- Dermatologiske midler
- Antibakterielle midler
- Antibiotika, antineoplastisk
- Reproduktive kontrolmidler
- Antituberkulære midler
- Abortfremkaldende midler, ikke-steroide
- Aborterende midler
- Folinsyreantagonister
- Antibiotika, Antituberkulær
- Calcineurin-hæmmere
- Cyclofosfamid
- Fludarabin
- Fludarabin phosphat
- Methotrexat
- Tacrolimus
- Mycophenolsyre
- Busulfan
- Antimfocyt serum
Andre undersøgelses-id-numre
- CDR0000463522
- UCSF-01251
- UCSF-H5010-19585-05
- UCSF-2101
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