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Low-Dose Fludarabine, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer

10 ottobre 2017 aggiornato da: University of California, San Francisco

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.

Panoramica dello studio

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

7

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

    • California
      • San Francisco, California, Stati Uniti, 94143-0324
        • UCSF Comprehensive Cancer Center

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 70 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Safety and Feasibility of donor cord blood transplant
Lasso di tempo: up to 36 months post transplant
as determined by > 80% engraftment rate at day 180 and a < 50% transplant-related mortality rate at day 100
up to 36 months post transplant

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Investigatori

  • Investigatore principale: Thomas G. Martin, MD, University of California, San Francisco

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 settembre 2004

Completamento primario (Effettivo)

1 luglio 2009

Completamento dello studio (Effettivo)

1 luglio 2009

Date di iscrizione allo studio

Primo inviato

9 marzo 2006

Primo inviato che soddisfa i criteri di controllo qualità

9 marzo 2006

Primo Inserito (Stima)

13 marzo 2006

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

12 ottobre 2017

Ultimo aggiornamento inviato che soddisfa i criteri QC

10 ottobre 2017

Ultimo verificato

1 ottobre 2017

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Altri numeri di identificazione dello studio

  • CDR0000465362
  • UCSF-04253
  • UCSF-2407
  • UCSF-H24045-25271-02

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

prodotto fabbricato ed esportato dagli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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