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Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Pilot Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source

NCT02167958

Description:

The purpose of this study is to determine whether stem cells collected from a donor's blood stream will be as safe and effective as using bone marrow collected from a donor's pelvic bone.

Related Conditions:
  • Acute Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Anaplastic Large Cell Lymphoma
  • Burkitt Lymphoma
  • Follicular Lymphoma
  • Hodgkin Lymphoma
  • Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Myelodysplastic Syndromes
  • Myelofibrosis
  • T-Cell Lymphoblastic Leukemia/Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Pilot Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source
  • Official Title: Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Pilot Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source

Clinical Trial IDs

  • ORG STUDY ID: 13-131
  • NCT ID: NCT02167958

Conditions

  • Leukemia
  • MDS
  • Myelofibrosis
  • Lymphoma

Interventions

DrugSynonymsArms
FludarabineFludaraTreatment
CyclophosphamideTreatment
MesnaMesnexTreatment
TacrolimusAstagraf XL, Hecoria, PrografTreatment
MycophenolateCellCept, MyforticTreatment
G-CSFGranulocyte - Colony Stimulating Factor, Filgrastim, Neupogen®Treatment

Purpose

The purpose of this study is to determine whether stem cells collected from a donor's blood stream will be as safe and effective as using bone marrow collected from a donor's pelvic bone.

Detailed Description

      This is a pilot study to assess the safety and potential efficacy of haploidentical
      peripheral blood stem cell transplantation using a nonmyeloablative preparative regimen and
      post-transplant cyclophosphamide. The overall objective of this study is to collect the
      efficacy and safety data to provide the basis to decide whether a larger study of clinical
      efficacy is warranted in this setting.
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalDay -6, -5 Fludarabine 30 mg/M2 IV over 30-60 minutes Cyclophosphamide 14.5 mg/kg IV over 1-2 hours*, Mesna 14.5 mg/kg IV in 4 divided doses Day -4 through -2 Fludarabine 30 mg/M2 IV over 30-60 minutes Day -1 Total Body Irradiation 200 cGy, donor apheresis Day 0 T cell replete PBSC Days 3, 4 Cyclophosphamide 50 mg/kg IV Mesna 50 mg/kg IV in 4 divided doses Day 5 Begin tacrolimus ,mycophenolate, and G-CSF
  • Fludarabine
  • Cyclophosphamide
  • Mesna
  • Tacrolimus
  • Mycophenolate
  • G-CSF

Eligibility Criteria

        Inclusion Criteria:

        Subject

          1. Age< 70.

          2. Molecular based HLA typing will be performed for the HLA-A, -B, -Cw, DRB1 and -DQB1
             loci to the resolution adequate to establish haplo identity. A minimum match of 5/10
             is required. An unrelated donor search is not required for a patient to be eligible
             for this protocol if the clinical situation dictates an urgent transplant. Clinical
             urgency is defined as 6-8 weeks from referral or low-likelihood of finding a matched,
             unrelated donor.

          3. Subjects must meet one of the disease classifications listed below:

             Acute leukemias (includes T lymphoblastic lymphoma). Remission is defined as < 5%
             blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a
             bone marrow with > 20% cellularity, peripheral blood counts showing ANC >1000/ul,
             including patients in CRp.

             Acute Lymphoblastic Leukemia in high risk CR1 as defined by at least one of the
             following:

             Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), MLL rearrangements White blood
             cell counts >30,000/mcL Patients over 30 years of age Time to complete remission >4
             weeks Presence of extramedullary disease

             Acute Myelogeneous Leukemia in high risk CR1 as defined by at least one of the
             following:

             Greater than 1 cycle of induction therapy required to achieve remission Preceding
             myelodysplastic syndrome (MDS) Presence of Flt3 abnormalities FAB M6 or M7 leukemia or

             Adverse cytogenetics for overall survival such as:

             those associated with MDS Complex karyotype (≥ 3 abnormalities) Any of the following:
             inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with other abnormalities except for
             t(8;21), t(9;11), inv(16) or t(16;16)], t(11;19)(q23;p13.1)

             Acute Leukemias in 2nd or subsequent remission

             Biphenotypic/Undifferentiated Leukemias in 1st or subsequent CR.

             High-risk MDS status-post cytotoxic chemotherapy

             Myelofibrosis

             Burkitt's lymphoma: second or subsequent CR.

             Lymphoma.

             Chemotherapy-sensitive (complete or partial response; see response criteria Appendix
             C) large cell, Mantle Cell or Hodgkin's lymphomas that have failed at least 1 prior
             regimen of multi-agent chemotherapy and are ineligible for an autologous transplant or
             relapsed/progressed after autologous stem cell transplant.

             Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at
             least two prior therapies (excluding single agent Rituxan) and are ineligible for an
             autologous transplant or relapsed/progressed after autologous stem cell transplant..

          4. Patients with adequate physical function as measured by:

             Cardiac: left ventricular ejection fraction at rest must be ≥ 35%.

             Hepatic: bilirubin ≤ 2.5 mg/dL; and ALT, AST, and Alkaline Phosphatase < 5 x ULN.

             Renal: serum creatinine within normal range for age, or if serum creatinine outside
             normal range for age, then renal function(creatinine clearance or GFR) > 40
             mL/min/1.73m2.

             Pulmonary: FEV1, FVC, DLCO (diffusion capacity) ≥ 40% predicted (corrected for
             hemoglobin); if unable to perform pulmonary function tests, then O2 saturation > 92%
             on room air.

             Performance status: Karnofsky/Lansky score ≥ 60%.

          5. Patients who have received a prior allogeneic HSCT and who have either rejected their
             grafts or who have become tolerant of their grafts with no active GVHD requiring
             immunosuppressive therapy.

        Donor

          1. Donors must be HLA-haploidentical first-degree or second degree relatives of the
             patient.

          2. Age ≥ 18 years

          3. Weight ≥ 40 kg

        Exclusion Criteria:

        Subject

          1. HLA-matched donor able to donate.

          2. Pregnancy or breast-feeding.

          3. Current uncontrolled bacterial, viral or fungal infection (currently taking medication
             with evidence of progression of clinical symptoms or radiologic findings).

        Donor

        1) Positive anti-donor HLA antibody.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Acute GvHD
Time Frame:Day +84
Safety Issue:
Description:The cumulative incidence of grades III/IV acute GvHD at day +84 will be assessed. The first day of acute GvHD onset will be used to calculate a cumulative incidence curve by certain grade. An overall cumulative incidence curve will be computed along with a 90% CI with graft failure, relapse/progression, and death as competing risks.

Secondary Outcome Measures

Measure:Neutrophil Recovery
Time Frame:Up to day +84
Safety Issue:
Description:Achievement of an ANC ≥ 500/mm3 for three consecutive measurements on different days. The first of the three days will be designated the day of neutrophil recovery.
Measure:Primary graft failure
Time Frame:Day +84
Safety Issue:
Description:Primary graft failure < 5% donor CD3 chimerism
Measure:Secondary graft failure
Time Frame:Up to 1 year
Safety Issue:
Description:Initial recovery followed by neutropenia with < 5% donor chimerism.
Measure:Platelet recovery
Time Frame:Up to day +84
Safety Issue:
Description:The first day of a sustained platelet count >20,000/mm3 with no platelet transfusions in the preceding seven days.
Measure:Donor Cell Engraftment
Time Frame:Day +28, Day >= +84
Safety Issue:
Description:Donor chimerism >= 50% on day >= 84 after transplantation. Donor engraftment also should be tested on day +28.
Measure:Progression-free Survival
Time Frame:Up to 1 year
Safety Issue:
Description:Progression-free survival is the minimum time interval to relapse/recurrence, to death or to last follow-up.
Measure:Infections
Time Frame:Date of onset
Safety Issue:
Description:Infections will be reported by anatomic site, date of onset, organism and resolution, if any.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Rafic Farah, MD

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