Clinical Trials /

URMC Related Haplo-identical Donor BMT

NCT02660281

Description:

This study will be a single-center treatment protocol, designed to validate the process of related donor haploidentical-SCT at the Wilmot Cancer Institute Blood and Marrow Transplant Unit.

Related Conditions:
  • Acute Biphenotypic Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Anaplastic Large Cell Lymphoma
  • Burkitt Leukemia
  • Burkitt Lymphoma
  • Chronic Myeloid Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Hodgkin Lymphoma
  • Malignant Solid Tumor
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Myelofibrosis
  • T-Cell Lymphoblastic Leukemia/Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: URMC Related Haplo-identical Donor BMT
  • Official Title: Haploidentical Donor Hematopoietic Stem Cell Transplantation

Clinical Trial IDs

  • ORG STUDY ID: UBMT 15056
  • NCT ID: NCT02660281

Conditions

  • Hematological Disease
  • Immune Deficiencies
  • Solid Tumors
  • Myelofibrosis
  • Multiple Myeloma
  • Lymphoma

Interventions

DrugSynonymsArms
FludarabineFull Intensity TBI-based Conditioning
Pre-Stem Cell Infusion CyclophosphamideFull Intensity Chemo-Only Conditioning
Pre-Stem Cell Infusion MesnaFull Intensity Chemo-Only Conditioning
BusulfanFull Intensity Chemo-Only Conditioning
MelphalanReduced Intensity Conditioning
Post-Stem Cell Infusion CyclophosphamideFull Intensity TBI-based Conditioning
Post-Stem Cell Infusion MesnaFull Intensity TBI-based Conditioning
ThiotepaReduced Intensity Conditioning with Addition of Thiotepa

Purpose

This study will be a single-center treatment protocol, designed to validate the process of related donor haploidentical-SCT at the Wilmot Cancer Institute Blood and Marrow Transplant Unit.

Detailed Description

      This study will be a single-center treatment protocol with five possible preparative
      regimens, designed to validate the process of related donor haploidentical-SCT at the Wilmot
      Cancer Institute Blood and Marrow Transplant Unit. Enrolled patients will receive
      chemotherapy +/- radiation as a pre-transplant conditioning regimen. Patients will then
      receive haploidentical stem cells, either bone marrow or mobilized peripheral blood, followed
      by GvHD prophylaxis that will include cyclophosphamide. Multiple data points will be
      collected prior to, during, and following transplantation to ensure safety of the process and
      to evaluate the stated objectives.
    

Trial Arms

NameTypeDescriptionInterventions
Full Intensity TBI-based ConditioningOtherTotal Body Irradiation 1200 cGy of 150 cGy over 4 or 5 days, days -5 or -4 to -1 Fludarabine 30 mg/m2/day x 3 days, days -6, -5, -4 Stem Cell Infusion, day 0 Post- Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Mesna 50 mg/kg/day x 2 days, days +3 and +4
  • Fludarabine
  • Post-Stem Cell Infusion Cyclophosphamide
  • Post-Stem Cell Infusion Mesna
Full Intensity Chemo-Only ConditioningOtherFludarabine 25 mg/m2/day x 5 days, days -6, -5, -4, -3, -2 Busulfan 130 mg/m2/day x 4 days, days -6, -5, -4, -3 Pre-Stem Cell Infusion Cyclophosphamide 14.5 mg/kg/day x 2 days, days -3 and -2 Pre-Stem Cell Infusion Mesna 14.5 mg/kg/day x 2 days, days -3 and -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell Infusion Mesna 50 mg/kg/day x 2 days, days +3 and +4
  • Fludarabine
  • Pre-Stem Cell Infusion Cyclophosphamide
  • Pre-Stem Cell Infusion Mesna
  • Busulfan
  • Post-Stem Cell Infusion Cyclophosphamide
  • Post-Stem Cell Infusion Mesna
Reduced Intensity ConditioningOtherFludarabine 30 mg/m2/day x 5 days, days -6 to -2 Melphalan 140 mg/m2/day x 1 day, day -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell InfusionMesna 50 mg/kg/day x 2 days, days +3 and +4
  • Fludarabine
  • Melphalan
  • Post-Stem Cell Infusion Cyclophosphamide
  • Post-Stem Cell Infusion Mesna
Non-Myeloablative ConditioningOtherFludarabine 30 mg/m2/day x 5 days, days -6 to -2 Pre-Stem Cell Infusion Cyclophosphamide 14.5 mg/kg/day x 2 days, days -3 and -2 Pre-Stem Cell InfusionMesna 14.5 mg/kg/day x 2 days, days -3 and -2 Total Body Irradiation 200 cGy, day -1 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, day +3 and +4 Post-Stem Cell Infusion Mesna 50 mg/kg/day x 2 days, day +3 and +4
  • Fludarabine
  • Pre-Stem Cell Infusion Cyclophosphamide
  • Pre-Stem Cell Infusion Mesna
  • Post-Stem Cell Infusion Cyclophosphamide
  • Post-Stem Cell Infusion Mesna
Reduced Intensity Conditioning with Addition of ThiotepaOtherFludarabine 30 mg/m2/day x 5 days, days -6 to -2 Thiotepa 8 mg/kg, day -3 Melphalan 140 mg/m2/day x 1 day, day -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell InfusionMesna 50 mg/kg/day x 2 days, days +3 and +4
  • Fludarabine
  • Melphalan
  • Post-Stem Cell Infusion Cyclophosphamide
  • Post-Stem Cell Infusion Mesna
  • Thiotepa

Eligibility Criteria

        Inclusion Criteria:

        Patient Age:

          -  Pediatric (ages 6 months to 18 years)

          -  Adult (ages 18-75 years)

        Disease:

        Congenital and Other Non-malignant Disorders

          -  Immunodeficiency disorders (e.g. Severe Combined Immunodeficiency, Wiskott-Aldrich
             Syndrome)

          -  Congenital hematopoietic stem cell defects (e.g. Chediak-Higashi Syndrome, Congenital
             Osteopetrosis, Osteogenesis Imperfecta)

          -  Metabolic disorders (e.g. Hurler's Syndrome)

          -  Hemoglobinopathies (e.g. Sickle Cell Disease, Thalassemia)

          -  Severe aplastic anemia

        High-Risk Leukemias

        Acute Myelogenous Leukemia

          -  Refractory to standard induction therapy (more than 1 cycle required to achieve
             remission)

          -  Recurrent (in CR≥2)

          -  Treatment-related AML or MDS

          -  Evolved from myelodysplastic syndrome

          -  Presence of Flt3 abnormalities

          -  FAB M6 or M7

          -  Adverse cytogenetics

        Myelodysplastic Syndrome

        Acute Lymphoblastic Leukemia including T lymphoblastic leukemia

          -  Refractory to standard induction therapy (time to CR >4 weeks)

          -  Recurrent (in CR ≥2)

          -  WBC count >30,000/mcL at diagnosis

          -  Age >30 at diagnosis

          -  Adverse cytogenetics, such as (t(9:22), t(1:19), t(4:11), other MLL rearrangements.

        Chronic Myelogenous Leukemia in accelerated phase or blast crisis

        Biphenotypic or undifferentiated leukemia

        Burkitt's leukemia or lymphoma

        Lymphoma:

          -  Large cell, Mantle cell, Hodgkin lymphoma refractory or recurrent, chemosensitive, and
             ineligible for an autologous stem cell transplant or previously treated with
             autologous SCT

          -  Marginal zone or follicular lymphoma that is progressive after at least two prior
             therapies

        Multiple Myeloma, recurrent following high-dose therapy and autologous SCT or ineligible
        for an autologous HSCT

        Solid tumors, with efficacy of allogeneic HSCT demonstrated for the specific disease and
        disease status

        Graft failure following prior related donor, unrelated donor or UCB transplant

        Myelofibrosis

        Exclusion Criteria:

          1. Patient Age below 6 months or over 75 years

          2. Availability of a 10/10 HLA-matched related or unrelated donor within a reasonable
             time-frame dictated by the clinical urgency of the transplant

          3. Autologous HSCT < 6 months prior to proposed haplo-SCT

          4. Pregnant or breast-feeding

          5. Current uncontrolled infection

          6. Evidence of HIV infection or positive HIV serology

          7. Anti-donor HLA antibodies with positive crossmatch and unsuccessful -
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:6 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The number of days from the date of the stem cell infusion to engraftment of absolute neutrophils (ANC) and platelets (PLT) will be determined based on daily CBC and differential counts.
Time Frame:42 days following the infusion of stem cells for ANC. [If engraftment of ANC does not occur within 42 days, a subsequent transplant will be performed if a donor is available.
Safety Issue:
Description:The date of engraftment of ANC is the first of 3 consecutive days of ANC of 500 or higher. The date of engraftment of platelets is the first of 3 consecutive days of platelet counts of 20,000 or higher in the absence of platelet transfusions for at least 7 days prior.

Secondary Outcome Measures

Measure:Percentage of subjects who develop acute graft-versus-host disease.
Time Frame:100 days following the infusion of stem cells
Safety Issue:
Description:Assess the presence and date of onset of acute GvHD based on the criteria published by Przepiorka et al., Bone Marrow Transplant 1995; 15(6):825-8 as used by the Center for International Blood & Marrow Transplant Research.
Measure:Assess the Maximum Overall Grades 0- IV of acute GvHD and Maximum Severity (0-4) by involved organ system in patients who develop acute graft-versus-host disease.
Time Frame:100 days following the infusion of stem cells
Safety Issue:
Description:Assess the severity of acute GvHD based on the criteria published by Przepiorka et al., Bone Marrow Transplant 1995; 15(6):825-8 as used by the Center for International Blood & Marrow Transplant Research.
Measure:Percentage of subjects who develop chronic graft-versus-host disease.
Time Frame:Minimally at intervals of 100 days, 6 months and then yearly following the infusion of stem cells until the subject's date of death.or up to 120 months.
Safety Issue:
Description:Calculate the percentage of patients who develop chronic graft-versus-host disease based on Sullivan KM, Blood 1981; 57:267 as used by the Center for International Blood & Marrow Transplant Research.
Measure:Assess the Maximum Grade: Limited versus Extensive; Maximum Severity: Mild, Moderate or Severe) of chronic GvHD in patients who develop chronic graft-versus-
Time Frame:Minimally at intervals of 100 days, 6 months and then yearly following the infusion of stem cells until the subject's date of death or up to 120 months.
Safety Issue:
Description:Assess the severity of chronic GvHD in patients who develop chronic graft-versus-host disease based on Sullivan KM, Blood 1981; 57:267 as used by the Center for International Blood & Marrow Transplant Research.
Measure:Disease-free survival
Time Frame:Disease assessments are performed and reported at time points that include 100 days, 6 months, and yearly until documented progression of disease or the date of death or up to 120 months.
Safety Issue:
Description:Document and update the length of time a subject survives without recurrence of the disease for which they were transplanted minimally at 100 days. 6 months, and yearly following the infusion of stem cells for as long as the patient survives and remains disease-free.
Measure:Time to relapsed disease
Time Frame:Disease assessments are performed and reported at time points that include 100 days, 6 months, and yearly until the date of documented progression or the subject's date of death or up to 120 months.
Safety Issue:
Description:Document the time to relapse of the disease for which the patient was Minimally assessments will be performed at 100 days. 6 months, and yearly following the infusion of stem cells for as long as the patient survives and remains disease-free.
Measure:Immune reconstitution
Time Frame:At 100 day, 6 month and one year intervals following the infusion of stem cells until the subject's date of death or up to 120 months.
Safety Issue:
Description:Evaluate immune reconstitution by measurement of immunoglobulins (IgG, IgA, and IgM), assessment of infections, and lymphocyte analysis

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Rochester

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