Clinical Trials /

Biparental HLA Haplotype Disparate T-cell Depleted Transplants for Patients Lacking an HLACompatible Donor

NCT01598025

Description:

Approximately 30% of patients who are candidates for bone marrow transplants do not have an HLA-matched, or close to matched, donor available. For this reason, doctors have been testing ways to make transplants from HLA-partially matched donors as safe and effective as transplants from HLA-matched donors. This study is being done to test the safety and the treatment results of a specific kind of transplant. In this transplant, blood from two donors will be used. Each donor will share one half of your HLA type. Blood from both donors will be transplanted at the same time.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Terminated

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Biparental HLA Haplotype Disparate T-cell Depleted Transplants for Patients Lacking an HLACompatible Donor
  • Official Title: Biparental HLA Haplotype Disparate T-cell Depleted Transplants for Patients Lacking an HLACompatible Donor

Clinical Trial IDs

  • ORG STUDY ID: 12-053
  • NCT ID: NCT01598025

Conditions

  • Acute Leukemia
  • Chronic Leukemia
  • Myelodysplastic Syndrome
  • Non-Hodgkins Lymphoma

Interventions

DrugSynonymsArms
thiotepaREGIMEN 1
fludarabine phosphateREGIMEN 1
melphalanRegimen 2
anti-thymocyte globulinREGIMEN 1
peripheral blood stem cell transplantationREGIMEN 1

Purpose

Approximately 30% of patients who are candidates for bone marrow transplants do not have an HLA-matched, or close to matched, donor available. For this reason, doctors have been testing ways to make transplants from HLA-partially matched donors as safe and effective as transplants from HLA-matched donors. This study is being done to test the safety and the treatment results of a specific kind of transplant. In this transplant, blood from two donors will be used. Each donor will share one half of your HLA type. Blood from both donors will be transplanted at the same time.

Trial Arms

NameTypeDescriptionInterventions
REGIMEN 1ExperimentalREGIMEN 1: Patients undergo hyperfractionated TBI TID for a total of 11-12 doses on days -10 to -7 and receive thiotepa IV over 4 hours QD on days -6 and -5, fludarabine phosphate IV over 30 minutes QD on days -6 to -2, and anti-thymocyte globulin IV on days -4 to -2. TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0.
  • thiotepa
  • fludarabine phosphate
  • anti-thymocyte globulin
  • peripheral blood stem cell transplantation
Regimen 2ExperimentalTo be given to patients non-malignant, life-threatening diseases and patients with hematologic malignancies, with extensive prior therapy and comorbidities who are unable to receive TBI, consists of Melphalan 70mg/m2 IV x 2 days, thiotepa 5mg/kg IV x 2 days (or 10mg/kg x 1 day), and fludarabine 25 mg/m2 IV x 5 days. TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0.
  • thiotepa
  • fludarabine phosphate
  • melphalan
  • anti-thymocyte globulin
  • peripheral blood stem cell transplantation

Eligibility Criteria

        Inclusion Criteria:

          -  Malignant conditions for which CD34+ selected, T-cell depleted allogeneic
             hematopoietic stem cell transplantation is indicated such as:

        AML in 1st remission - for patients whose AML does not have 'good risk' cytogenetic
        features (i.e. t 8;21, t15;17, inv 16).

          -  Secondary AML in 1st remission

          -  AML in 1st relapse or > 2nd remission

          -  ALL/LL in 1st remission clinical or molecular features indicating a high risk for
             relapse; or ALL > 2nd remission

          -  CML failing to respond to or not tolerating Imatinib, dasatinib, or nilotinib in first
             chronic phase of disease; or CML in accelerated phase or second chronic phase.

          -  Non-Hodgkins lymphoma with chemoresponsive disease in any of the following categories:
             a) intermediate or high grade lymphomas who have failed to achieve a first CR or have
             relapsed following a 1st remission who are not candidates for autologous transplants.

          -  any NHL in remission which is considered not curable with chemotherapy alone and not
             eligible/appropriate for autologous transplant. Myelodysplastic syndrome (MDS):
             RA/RCMD with high risk cytogenetic features or transfusion dependence, RAEB-1 and
             RAEB-2 and Acute myelogenous leukemia (AML) evolved from MDS, who are not eligible for
             transplantation under protocol IRB 08-008.

          -  Chronic myelomonocytic leukemia: CMML-1 and CMML-2.

          -  Other rare lethal disorders of Hematopoiesis and Lymphopoiesis for which a T-cell
             depleted transplant is indicated (e.g. hemophagocytic lymphohistiocytosis; refractory
             aplastic anemia or conjugated cytopenias; non-SCID lethal genetic immunodeficiencies
             such as Wiskott Aldrich Syndrome, CD40 ligand deficiency, ALPS).

          -  Patients may be of either gender and of any racial or ethnic background.

          -  Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status > 70%.

          -  Patients must have adequate organ function measured by:

        Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50% and must improve
        with exercise.

          -  Hepatic: < 3x ULN ALT and < 2.0x ULN total serum bilirubin, unless there is congenital
             benign hyperbilirubinemia.

          -  Renal: serum creatinine <1.2 mg/dl or if serum creatinine is outside the normal range,
             then CrCl > 40 ml/min (measured or calculated/estimated)

          -  Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for
             hemoglobin)

          -  Each patient must be willing to participate as a research subject and must sign an
             informed consent form.

        Exclusion Criteria:

          -  Female patients who are pregnant or breast-feeding

          -  Uncontrolled viral, bacterial or fungal infection

          -  Patient seropositive for HIV-I/II; HTLV -I/II

          -  Presence of leukemia in the CNS.

        Donor Inclusion Criteria:

          -  Each donor must meet criteria outlined by institutional policies

          -  Donor must have adequate peripheral venous catheter access for leukapheresis or must
             agree to placement of a central catheter.

        Donor Exclusion Criteria:

          -  Evidence of active infection (including urinary tract infection, or upper respiratory
             tract infection), viral hepatitis exposure (on screening), unless only HBS Ab+ and HBV
             DNA negative, or serologic evidence of exposure or infection with HIV-I/II or
             HTLV-I/II

          -  If donors do not meet institutional guidelines, exclusion will be considered.
      
Maximum Eligible Age:19 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Efficacy of HLA-haploidentical Biparental T-cell Depleted CD34+ Peripheral Blood Stem Cell Transplants
Time Frame:1 year
Safety Issue:
Description:Efficacy is measured by: incidence of transplant-related mortality, overall survival and disease-free survival at 1 year post transplant. incidence, tempo and complications of engraftment and hematopoietic reconstitutions and conversely, the risk of graft failure incidence and severity of acute and/or chronic GVHD incidence and severity of opportunistic infections developing following engraftment

Secondary Outcome Measures

Measure:Evaluation of Recipients Post Transplant
Time Frame:1 year
Safety Issue:
Description:The levels of engraftment and persistence of hematopoietic cells and their myeloid and lymphoid progressing from each donor post transplant. The tolerance or reactivity of engrafted T cells from each donor detected in the blood at 3, 6, and thereafter every 3-6 months until normal, post transplant against host cells and cells derived from the other parent as measured by standard mixed lymphocyte culture and cell mediated cytolysis assays.

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • ANTITHYMOCYTE GLOBULIN:ATG
  • FLUDARABINE
  • THI0TEPA
  • CliniMACS-CD34 Reagent System
  • 12-053

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