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

NCT01598025 | Terminated Results

• 1 other identifier: 12-053
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Leukemia; Chronic Leukemia; Myelodysplastic Syndrome; Non-Hodgkins Lymphoma

Keywords

ANTITHYMOCYTE GLOBULIN:ATG; FLUDARABINE; THI0TEPA; CliniMACS-CD34 Reagent System; 12-053

Outcome Measures

Primary Outcomes (1)

• Efficacy of HLA-haploidentical Biparental T-cell Depleted CD34+ Peripheral Blood Stem Cell Transplants

  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 Outcomes (1)

• Evaluation of Recipients Post Transplant

  1 year

Study Arms (2)

REGIMEN 1

EXPERIMENTAL

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

Regimen 2

EXPERIMENTAL

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

Interventions

total-body irradiation (TBI) RADIATION

REGIMEN 1

thiotepa DRUG

REGIMEN 1; Regimen 2

fludarabine phosphate DRUG

REGIMEN 1; Regimen 2

melphalan DRUG

Regimen 2

anti-thymocyte globulin BIOLOGICAL

REGIMEN 1; Regimen 2

allogeneic hematopoietic stem cell transplantation PROCEDURE

REGIMEN 1; Regimen 2

peripheral blood stem cell transplantation BIOLOGICAL

REGIMEN 1; Regimen 2

laboratory biomarker analysis OTHER

REGIMEN 1; Regimen 2

Eligibility Criteria

• Age: Up to 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065-0009, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin

Interventions

Whole-Body Irradiation; Thiotepa; fludarabine phosphate; Melphalan; Antilymphocyte Serum; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Richard O'Reilly, MD
• Organization: Memorial Sloan Kettering Cancer Center

oreillyr@mskcc.org

646-888-2157

Study Officials

• Richard O'Reilly, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2012
• First Posted: May 15, 2012
• Study Start: May 2, 2012
• Primary Completion: October 16, 2017
• Study Completion: October 16, 2017
• Last Updated: August 9, 2018
• Results First Posted: April 17, 2018

Record last verified: 2018-07

Locations

US (1)