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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01598025
First received: May 9, 2012
Last updated: May 14, 2014
Last verified: May 2014
  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.


Condition Intervention 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
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Biparental HLA Haplotype Disparate T-cell Depleted Transplants for Patients Lacking an HLACompatible Donor

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • efficacy [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    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:
  • evaluate recipients post transplant [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 50
Study Start Date: May 2012
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 30 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

  Eligibility

Ages Eligible for Study:   up to 19 Years
Genders Eligible for Study:   Both
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01598025

Contacts
Contact: Richard O'Reilly, MD 212-639-5956
Contact: Nancy Kernan, MD 212-639-7250

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065-0009
Contact: Richard O'Reilly, MD    212-639-5956      
Contact: Nancy Kernan, MD    212-639-7250      
Principal Investigator: Richard O'Reilly, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Richard O'Reilly, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01598025     History of Changes
Other Study ID Numbers: 12-053
Study First Received: May 9, 2012
Last Updated: May 14, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on August 26, 2014