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

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ClinicalTrials.gov Identifier: NCT01598025
Recruitment Status : Terminated (Closed due to poor accrual)
First Posted : May 15, 2012
Results First Posted : April 17, 2018
Last Update Posted : August 9, 2018
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE May 9, 2012
First Posted Date  ICMJE May 15, 2012
Results First Submitted Date  ICMJE March 19, 2018
Results First Posted Date  ICMJE April 17, 2018
Last Update Posted Date August 9, 2018
Actual Study Start Date  ICMJE May 2, 2012
Actual Primary Completion Date October 16, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 12, 2018)
Efficacy of HLA-haploidentical Biparental T-cell Depleted CD34+ Peripheral Blood Stem Cell Transplants [ Time Frame: 1 year ]
Efficacy is measured by:
  1. incidence of transplant-related mortality, overall survival and disease-free survival at 1 year post transplant.
  2. incidence, tempo and complications of engraftment and hematopoietic reconstitutions and conversely, the risk of graft failure
  3. incidence and severity of acute and/or chronic GVHD
  4. incidence and severity of opportunistic infections developing following engraftment
Original Primary Outcome Measures  ICMJE
 (submitted: May 10, 2012)
efficacy [ Time Frame: 1 year ]
measured by:
  1. incidence of transplant-related mortality, overall survival and disease-free survival at 1 year post transplant.
  2. incidence, tempo and complications of engraftment and hematopoietic reconstitutions and conversely, the risk of graft failure
  3. incidence and severity of acute and/or chronic GVHD
  4. incidence and severity of opportunistic infections developing following engraftment
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 12, 2018)
Evaluation of Recipients Post Transplant [ Time Frame: 1 year ]
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2012)
evaluate recipients post transplant [ Time Frame: 1 year ]
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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Biparental HLA Haplotype Disparate T-cell Depleted Transplants for Patients Lacking an HLACompatible Donor
Official Title  ICMJE Biparental HLA Haplotype Disparate T-cell Depleted Transplants for Patients Lacking an HLACompatible Donor
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Leukemia
  • Chronic Leukemia
  • Myelodysplastic Syndrome
  • Non-Hodgkins Lymphoma
Intervention  ICMJE
  • Radiation: total-body irradiation (TBI)
  • Drug: thiotepa
  • Drug: fludarabine phosphate
  • Drug: melphalan
  • Biological: anti-thymocyte globulin
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Biological: peripheral blood stem cell transplantation
  • Other: laboratory biomarker analysis
Study Arms  ICMJE
  • Experimental: REGIMEN 1

    REGIMEN 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.

    Interventions:
    • Radiation: total-body irradiation (TBI)
    • Drug: thiotepa
    • Drug: fludarabine phosphate
    • Biological: anti-thymocyte globulin
    • Procedure: allogeneic hematopoietic stem cell transplantation
    • Biological: peripheral blood stem cell transplantation
    • Other: laboratory biomarker analysis
  • Experimental: Regimen 2

    To 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.

    Interventions:
    • Drug: thiotepa
    • Drug: fludarabine phosphate
    • Drug: melphalan
    • Biological: anti-thymocyte globulin
    • Procedure: allogeneic hematopoietic stem cell transplantation
    • Biological: peripheral blood stem cell transplantation
    • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 31, 2016)
3
Original Estimated Enrollment  ICMJE
 (submitted: May 10, 2012)
40
Actual Study Completion Date  ICMJE October 16, 2017
Actual Primary Completion Date October 16, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 19 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01598025
Other Study ID Numbers  ICMJE 12-053
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Richard O'Reilly, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP