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Cyclophosphamide and/or Mycophenolate Mofetil With or Without Tacrolimus in Treating Patients Who Are Undergoing a Donor Bone Marrow or Peripheral Stem Cell Transplant for Hematologic Cancer

Nonmyeloablative Bone Marrow Transplants in Hematologic Malignancies: Dose Finding Study for Post-Transplant Immunosuppression

RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor bone marrow or stem cell transplant 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). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclophosphamide, mycophenolate mofetil, and tacrolimus after transplant may stop this from happening.

PURPOSE: This phase I trial is studying cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus to see which is the best regimen in treating patients who are undergoing a donor bone marrow or stem cell transplant for hematologic cancer.

Descripción general del estudio

Descripción detallada

OBJECTIVES:

  • Determine a minimal (short-duration) post-transplant immunosuppression regimen comprising cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus that results in ≤ 20% incidence of grade II or higher acute graft-versus-host disease (GVHD) in patients with hematologic malignancies undergoing nonmyeloablative allogeneic bone marrow or peripheral blood stem cell transplantation from an HLA-identical related donor.
  • Determine the post-transplant immunosuppression regimen that results in < 10% incidence of nonengraftment, defined as < 5% donor chimerism in peripheral blood at day 60, in these patients.
  • Determine the incidence and severity of acute GVHD in patients treated with these regimens.
  • Determine the frequency of mixed chimerism in patients treated with these regimens.

OUTLINE:

  • Nonmyeloablative allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT): Patients receive fludarabine IV on days -4 to -2 and undergo total-body irradiation on day -1. Patients undergo allogeneic BMT on day 0 or PBSCT on day 0 (and days 1 and 2, if needed). Patients receive filgrastim (G-CSF) beginning on day 5 and continuing until at least day 15 or until blood counts recover.
  • Sequentially increasing levels of post-transplant immunosuppression: Cohorts of patients are enrolled into 1 of the following regimens:

    • Regimen 1 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on day 3 only.
    • Regimen 2 (post-BMT immunosuppression): Patients receive mycophenolate mofetil (MMF) once on day 3 and then twice daily on days 4-32.
    • Regimen 3 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on days 3 and 4 and MMF twice daily on days 4-33.
    • Regimen 4 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF as in regimen 3.
    • Regimen 5 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF as in regimen 3 and tacrolimus twice daily on days 4-33.

Cohorts of approximately 10-20 patients receive sequentially increasing levels of post-transplant immunosuppression until a minimal (short-duration) post-transplant immunosuppression regimen is identified. The minimal post-transplant immunosuppression regimen is defined as the regimen in which ≤ 3 of 10 or ≤ 6 of 20 patients develop grade II or higher acute graft-versus-host disease AND ≤ 2 of 10 or ≤ 4 of 20 patients fail to engraft 60 days post-transplantation. Once the minimal post-transplant immunosuppression regimen is identified, an additional 10 patients are treated with that regimen.

Patients are followed for 60 days after transplantation.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Tipo de estudio

Intervencionista

Inscripción (Anticipado)

60

Fase

  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

    • Maryland
      • Baltimore, Maryland, Estados Unidos, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 75 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following hematologic malignancies:

    • Stage II or III multiple myeloma
    • Amyloidosis
    • Myelofibrosis with ≥ 2 of the following high-risk features:

      • Over 55 years of age
      • Hemoglobin < 10 g/dL
      • WBC < 3,000/mm^3 OR > 10,000/mm^3
      • Platelet count < 100,000/mm^3
      • Cytogenetic abnormalities
    • Mycosis fungoides, meeting 1 of the following criteria:

      • Stage IIB or III disease with evidence of histologic conversion to an aggressive lymphoma

        • Must demonstrate chemosensitivity
      • Stage IV disease
    • Paroxysmal nocturnal hemoglobinuria

      • Not meeting criteria for other bone marrow transplantation (BMT) or treatment studies
    • Diagnosis of 1 of the following hematologic malignancies, for which patient is not eligible for potentially curative allogeneic BMT due to end-organ dysfunction, age 65 to 75, or the amount of prior chemotherapy:

      • Acute myeloid or acute lymphoblastic leukemia

        • High-risk disease in first or second (or further) complete remission
      • Relapsed aggressive non-Hodgkin's lymphoma

        • Not eligible for autologous or standard allogeneic BMT
      • Hodgkin's lymphoma in second or further complete or partial remission

        • Not eligible for autologous or standard allogeneic BMT
      • Myelodysplastic syndromes or myelodysplastic/myeloproliferative diseases

        • Any of the following subtypes:

          • Refractory anemia with excess blasts (RAEB)
          • RAEB in transformation
          • Chronic myelomonocytic leukemia
          • Any morphologic subtype with multiple chromosomal abnormalities
          • Any subset with life-threatening cytopenias in all 3 cell lines, defined as platelet count ≤ 20,000/mm^3, absolute neutrophil count ≤ 500/mm^3, and reticulocyte count ≤ 50,000/mm^3
        • Meets both of the following criteria:

          • Less than 20% blasts by bone marrow biopsy
          • Not eligible for standard allogeneic BMT
        • No refractory anemia with ringed sideroblasts
        • No 5q syndrome
      • Stage III or IV chronic lymphocytic leukemia

        • Not meeting criteria for other BMT studies
      • Chronic myelogenous leukemia in first or second chronic phase

        • Not meeting criteria for other BMT studies or treatment
      • Stage III or IV indolent small lymphocytic or follicular lymphoma

        • Not eligible for autologous or standard allogeneic BMT or other active protocols at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Must have an HLA-identical related donor available

PATIENT CHARACTERISTICS:

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin ≤ 3.0 mg/dL
  • AST ≤ 175 U/L
  • ALT ≤ 200 U/L

Renal

  • Creatinine ≤ 3.0 mg/dL

Cardiovascular

  • LVEF ≥ 30%

Pulmonary

  • FEV_1 ≥ 40% predicted
  • Forced vital capacity ≥ 40% predicted

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative

PRIOR CONCURRENT THERAPY:

Chemotherapy

  • See Disease Characteristics

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Cuidados de apoyo
  • Enmascaramiento: Ninguno (etiqueta abierta)

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Post-transplant immunosuppression regimen with ≤ 20% incidence of a grade II-IV graft-versus-host-disease (GVHD) and < 10% incidence of nonengraftment (< 5% donor chimerism) at day 60 following transplant
Incidence and severity of acute GVHD at day 60 following transplant
Frequency of mixed chimerism defined as any detectable donor cells at day 60 following transplant

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Investigadores

  • Silla de estudio: Carol A. Huff, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de julio de 2002

Fechas de registro del estudio

Enviado por primera vez

18 de noviembre de 2005

Primero enviado que cumplió con los criterios de control de calidad

18 de noviembre de 2005

Publicado por primera vez (Estimar)

21 de noviembre de 2005

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

17 de marzo de 2010

Última actualización enviada que cumplió con los criterios de control de calidad

16 de marzo de 2010

Última verificación

1 de marzo de 2010

Más información

Términos relacionados con este estudio

Palabras clave

Otros números de identificación del estudio

  • CDR0000449652
  • P30CA006973 (Subvención/contrato del NIH de EE. UU.)
  • P01CA015396 (Subvención/contrato del NIH de EE. UU.)
  • JHOC-J0169
  • WIRB-20020304

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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