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- Klinische proef NCT00301951
Low-Dose Fludarabine, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer
Pilot Study of Reduced-Intensity Umbilical Cord Blood Transplantation in Adult Patients With Advanced Hematopoietic Malignancies
RATIONALE: Giving chemotherapy before a donor umbilical cord blood transplant helps stop both the growth of cancer cells and the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving chemotherapy, such as fludarabine and busulfan, and antithymocyte globulin before transplant and tacrolimus and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This clinical trial is studying how well giving low-dose fludarabine and busulfan together with anti-thymocyte globulin, followed by donor umbilical cord blood transplant works in treating patients with advanced hematologic cancer.
Studie Overzicht
Toestand
Gedetailleerde beschrijving
OBJECTIVES:
Primary
- Assess the feasibility of performing umbilical cord blood transplants in older patients or younger infirm patients with advanced hematologic malignancies using a reduced-intensity preparative regimen, as determined by > 80% engraftment rate at day 180 and a < 50% transplant-related mortality rate at day 100.
Secondary
- Describe the time to neutrophil and platelet recovery in patients treated with this regimen.
- Determine disease-specific, event-free, and overall survival rate at days 180 and 360.
- Determine the incidence, severity, and timing of acute and chronic graft-versus-host disease in patients treated with this regimen.
- Evaluate T-cell, B-cell, and natural killer cell recovery in patients treated with this regimen.
- Assess lineage-specific chimerism after transplantation and describe the contribution of each individual cord blood unit to post-transplantation hematopoiesis.
OUTLINE: This is a pilot study.
- Reduced-intensity preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4, busulfan IV over 2 hours 4 times daily on days -4 and -3, and anti-thymocyte globulin IV over 6 hours on days -3 to -1.
- Allogeneic umbilical cord blood transplantation: Patients undergo allogeneic umbilical cord blood transplant on day 0. Patients receive sargramostim (GM-CSF) subcutaneously or IV beginning on day 7 and continuing until blood counts recover.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously over 24 hours or orally (as tolerated) beginning on day -2 and continuing for approximately 9 months. Patients also receive oral mycophenolate mofetil twice daily on days 1-50.
After completion of study treatment, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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California
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San Francisco, California, Verenigde Staten, 94143-0324
- UCSF Comprehensive Cancer Center
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
DISEASE CHARACTERISTICS:
Diagnosis of 1 of the following advanced hematologic malignancies:
Acute myeloid leukemia (AML) meeting the following criteria:
- Considered incurable with chemotherapy
- Marrow blasts ≤ 10% (may be achieved using standard chemotherapy regimen)
Meets any of the following criteria:
- High-risk cytogenetics (-7, -7q, -5, -5q, t(6,9), t(9,11), complex [≥ 3 abnormalities], Philadelphia chromosome positive [Ph+])
- AML evolved from prior myelodysplasia
- AML secondary to prior chemotherapy
- Failed to achieve remission
- In second or subsequent remission
- Refractory relapse
Myelodysplastic syndromes (MDS) meeting the following criteria:
Must have high-risk features, including any of the following:
- Intermediate-2 or high risk International Prognostic Scoring System (IPSS) score
- Chronic myelomonocytic leukemia
- Marrow blasts ≤ 20% (chemotherapy may be given to achieve target blast levels)
- No rapidly progressive disease
Acute lymphoblastic leukemia meeting the following criteria:
- Considered incurable with chemotherapy
Meets any of the following criteria:
- High-risk cytogenetics (Ph+, t(4,11), 11q23 abnormalities, or monosomy 7)
- Required > 1 induction course to achieve remission
- Failed to enter remission
- In second or subsequent remission
- Marrow blasts ≤ 10% (chemotherapy may be given to achieve target blast levels)
Chronic myelogenous leukemia (CML) meeting 1 of the following criteria:
- Chronic phase CML that failed imatinib mesylate therapy, as defined by progressive disease or failed to achieve a major cytogenetic response at 1 year after initiation of therapy
Accelerated phase CML meeting 1 of the following criteria:
- Failed to achieve a complete cytogenetic remission at 1 year after initiation of therapy
- Failed to achieve any cytogenetic response after 6 months of therapy
- Progressive disease, as demonstrated by worsening cytogenetic response in 2 consecutive analyses separated by 4 weeks
- In blast crisis with < 10% blasts in bone marrow
Multiple myeloma meeting the following criteria:
- Stage I-III disease
Meets any of the following criteria:
- In relapse after autologous transplantation
- Refractory to ≥ 2 prior conventional myeloma therapies
- Chromosome 13 abnormalities (may be enrolled at diagnosis or after initial progression)
Lymphoma
The following subtypes are eligible:
- Diffuse large cell
- Follicular large cell
- Mantle cell
- Peripheral T-cell
- T-natural killer (T-NK) cell
- Hodgkin's lymphoma
- Must have progressed, recurred after prior therapy, or failed to respond to primary therapy
- Relapsed disease after autologous stem cell transplantation (SCT) allowed
Low-grade non-Hodgkin's lymphoma meeting 1 of the following criteria:
- Relapsed or refractory disease after ≥ 2 chemotherapy-based treatment regimens
- Relapsed after autologous SCT
Chronic lymphocytic leukemia
- Relapsed or refractory disease after ≥ 2 chemotherapy-based treatment regimens
- Relapsed after autologous SCT
Meets 1 of the following criteria:
- Age 55-70 years
Under age 55 and deemed ineligible for conventional high-dose chemotherapy, as indicated by any of the following:
- Poor cardiac function (i.e., LVEF < 40%)
- Poor pulmonary function (i.e., DLCO < 50%)
- Hepatic dysfunction
- Prior myeloablative therapy
- Not eligible for autologous SCT or conventional therapy
Umbilical cord blood donor available
- Matched at ≥ 4 of 6 HLA antigens (A, B, and DR)
- Has 1-3 units of umbilical cord blood available
- Must not have an HLA-identical or 1 antigen mismatched related donor or potential HLA-matched unrelated donor readily available 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:
- ECOG performance status 0-2
- Creatinine clearance > 40 mL/min
- Creatinine < 2.0 mg/dL
- AST and alkaline phosphatase < 3 times upper limit of normal (ULN)
- Bilirubin < 2.0 mg/dL
Hepatitis C or active hepatitis B virus (HBV) allowed if ≤ grade 2 fibrosis and/or inflammation by liver biopsy
- Patients with history of HBV infection should be tested for hepatitis B epsilon (HBe) antigen, anti-HBe, and HBV DNA (quantitative)
- Patients with active HBV viral replication should receive antiviral therapy
- Ejection fraction > 30%
- DLCO ≥ 40%
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active infection requiring ongoing antibiotic treatment
- HIV negative
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: navelstrengbloed transplantatie
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Safety and Feasibility of donor cord blood transplant
Tijdsspanne: up to 36 months post transplant
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as determined by > 80% engraftment rate at day 180 and a < 50% transplant-related mortality rate at day 100
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up to 36 months post transplant
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Medewerkers en onderzoekers
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Thomas G. Martin, MD, University of California, San Francisco
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
- stadium III volwassen diffuus grootcellig lymfoom
- stadium IV graad 3 folliculair lymfoom
- stadium IV volwassen diffuus grootcellig lymfoom
- recidiverend graad 3 folliculair lymfoom
- recidiverend diffuus grootcellig lymfoom bij volwassenen
- chronische myelomonocytaire leukemie
- de novo myelodysplastische syndromen
- eerder behandelde myelodysplastische syndromen
- secundaire myelodysplastische syndromen
- volwassen acute myeloïde leukemie met 11q23 (MLL) afwijkingen
- volwassen acute myeloïde leukemie met inv(16)(p13;q22)
- volwassen acute myeloïde leukemie met t(15;17)(q22;q12)
- volwassen acute myeloïde leukemie met t(16;16)(p13;q22)
- volwassen acute myeloïde leukemie met t(8;21)(q22;q22)
- secundaire acute myeloïde leukemie
- chronische fase chronische myeloïde leukemie
- recidiverende volwassen acute myeloïde leukemie
- volwassen acute myeloïde leukemie in remissie
- recidiverend volwassen Hodgkin-lymfoom
- blastische fase chronische myeloïde leukemie
- recidiverende chronische myeloïde leukemie
- stadium III graad 1 folliculair lymfoom
- stadium III graad 2 folliculair lymfoom
- stadium III graad 3 folliculair lymfoom
- stadium IV graad 1 folliculair lymfoom
- stadium IV graad 2 folliculair lymfoom
- stadium III mantelcellymfoom
- stadium IV mantelcellymfoom
- stadium II multipel myeloom
- stadium III multipel myeloom
- recidiverend graad 1 folliculair lymfoom
- recidiverend graad 2 folliculair lymfoom
- recidiverend marginale zone-lymfoom
- terugkerend klein lymfocytisch lymfoom
- stadium III klein lymfocytisch lymfoom
- stadium III marginale zone lymfoom
- stadium IV klein lymfocytisch lymfoom
- stadium IV marginale zone lymfoom
- extranodale marginale zone B-cellymfoom van mucosa-geassocieerd lymfoïde weefsel
- nodale marginale zone B-cellymfoom
- milt marginale zone lymfoom
- stadium I multipel myeloom
- terugkerend mantelcellymfoom
- refractaire chronische lymfatische leukemie
- stadium III chronische lymfatische leukemie
- stadium IV chronische lymfatische leukemie
- stadium III volwassen Hodgkin-lymfoom
- stadium IV volwassen Hodgkin-lymfoom
- recidiverend cutaan T-cel non-Hodgkin-lymfoom
- stadium III volwassen T-cel leukemie/lymfoom
- stadium IV volwassen T-cel leukemie/lymfoom
- recidiverende volwassen T-cel leukemie/lymfoom
- angioimmunoblastisch T-cellymfoom
- anaplastisch grootcellig lymfoom
- recidiverende mycosis fungoides/Sezary-syndroom
- refractair multipel myeloom
- recidiverende volwassen acute lymfatische leukemie
- versnelde fase chronische myeloïde leukemie
- volwassen acute lymfatische leukemie in remissie
Aanvullende relevante MeSH-voorwaarden
- Pathologische processen
- Hart-en vaatziekten
- Vaatziekten
- Ziekten van het immuunsysteem
- Neoplasmata per histologisch type
- Neoplasmata
- Lymfoproliferatieve aandoeningen
- Lymfatische ziekten
- Immunoproliferatieve aandoeningen
- Ziekte
- Beenmergziekten
- Hematologische ziekten
- Hemorragische aandoeningen
- Hemostatische aandoeningen
- Paraproteïnemieën
- Bloed eiwit stoornissen
- Voorstadia van kanker
- Lymfoom
- Syndroom
- Myelodysplastische syndromen
- Multipel myeloom
- Neoplasmata, plasmacel
- Leukemie
- Preleukemie
- Plasmacytoom
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Anti-infectieuze middelen
- Enzymremmers
- Antimetabolieten, antineoplastische
- Antimetabolieten
- Antineoplastische middelen
- Immunosuppressieve middelen
- Immunologische factoren
- Antineoplastische middelen, alkylering
- Alkyleringsmiddelen
- Myeloablatieve agonisten
- Antibacteriële middelen
- Antibiotica, antineoplastiek
- Antituberculeuze middelen
- Antibiotica, antituberculair
- Calcineurineremmers
- Fludarabine
- Fludarabine-fosfaat
- Tacrolimus
- Mycofenolzuur
- Busulfan
- Sargramostim
- Antilymfocyten Serum
Andere studie-ID-nummers
- CDR0000465362
- UCSF-04253
- UCSF-2407
- UCSF-H24045-25271-02
Informatie over medicijnen en apparaten, studiedocumenten
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