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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

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.


Condition or disease Intervention/treatment Phase
Acute Leukemia Chronic Leukemia Myelodysplastic Syndrome Non-Hodgkins Lymphoma 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 Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Biparental HLA Haplotype Disparate T-cell Depleted Transplants for Patients Lacking an HLACompatible Donor
Actual Study Start Date : May 2, 2012
Actual Primary Completion Date : October 16, 2017
Actual Study Completion Date : October 16, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

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.

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



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   up to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01598025


Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065-0009
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
Principal Investigator: Richard O'Reilly, MD Memorial Sloan Kettering Cancer Center
  Study Documents (Full-Text)

Documents provided by Memorial Sloan Kettering Cancer Center:

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01598025     History of Changes
Other Study ID Numbers: 12-053
First Posted: May 15, 2012    Key Record Dates
Results First Posted: April 17, 2018
Last Update Posted: August 9, 2018
Last Verified: July 2018

Keywords provided by Memorial Sloan Kettering Cancer Center:
ANTITHYMOCYTE GLOBULIN:ATG
FLUDARABINE
THI0TEPA
CliniMACS-CD34 Reagent System
12-053

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoma
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine
Fludarabine phosphate
Melphalan
Thiotepa
Antilymphocyte Serum
Vidarabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Antineoplastic Agents, Alkylating