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

NCT ID: NCT01598025

Last Updated: 2018-08-09

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-02

Study Completion Date

2017-10-16

Brief Summary

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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

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Conditions

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Acute Leukemia Chronic Leukemia Myelodysplastic Syndrome Non-Hodgkins Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

total-body irradiation (TBI)

Intervention Type RADIATION

thiotepa

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

anti-thymocyte globulin

Intervention Type BIOLOGICAL

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type BIOLOGICAL

laboratory biomarker analysis

Intervention Type OTHER

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.

Group Type EXPERIMENTAL

thiotepa

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

melphalan

Intervention Type DRUG

anti-thymocyte globulin

Intervention Type BIOLOGICAL

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type BIOLOGICAL

laboratory biomarker analysis

Intervention Type OTHER

Interventions

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total-body irradiation (TBI)

Intervention Type RADIATION

thiotepa

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

melphalan

Intervention Type DRUG

anti-thymocyte globulin

Intervention Type BIOLOGICAL

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type BIOLOGICAL

laboratory biomarker analysis

Intervention Type OTHER

Eligibility Criteria

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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.


* 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.

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.


* 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

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Richard O'Reilly, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://www.mskcc.org/

Memorial Sloan Kettering Cancer Center

Other Identifiers

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12-053

Identifier Type: -

Identifier Source: org_study_id

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