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

July 12, 2018 updated by: Memorial Sloan Kettering Cancer Center

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065-0009
        • Memorial Sloan Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 19 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / 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.
Other: laboratory biomarker analysis
Drug: thiotepa
Biological: anti-thymocyte globulin
Drug: fludarabine phosphate
Procedure: allogeneic hematopoietic stem cell transplantation
Radiation: total-body irradiation (TBI)
Biological: peripheral blood stem cell transplantation
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.
Other: laboratory biomarker analysis
Drug: thiotepa
Biological: anti-thymocyte globulin
Drug: fludarabine phosphate
Procedure: allogeneic hematopoietic stem cell transplantation
Drug: melphalan
Biological: peripheral blood stem cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 2, 2012

Primary Completion (ACTUAL)

October 16, 2017

Study Completion (ACTUAL)

October 16, 2017

Study Registration Dates

First Submitted

May 9, 2012

First Submitted That Met QC Criteria

May 10, 2012

First Posted (ESTIMATE)

May 15, 2012

Study Record Updates

Last Update Posted (ACTUAL)

August 9, 2018

Last Update Submitted That Met QC Criteria

July 12, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12-053

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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