Optimizing Cord Blood and Haploidentical Aplastic Anemia Transplantation (BMT CTN 1502)

Description

This study is a prospective, simultaneous, parallel phase II study with one arm receiving unrelated cord blood transplantation and the other arm receiving haploidentical transplantation for Severe Aplastic Anemia (SAA) patients. The primary objective is to assess overall survival (OS) separately in the 2 arms at 1 year post-hematopoietic stem cell transplantation (HSCT).

Study Start Date

May, 19 2017

Estimated Completion Date

February 2022

Interventions

  • Drug: Antithymocyte Globulin
  • Procedure: Haplo HSCT
  • Drug: Cyclophosphamide
  • Radiation: Total Body Irradiation (TBI)
  • Procedure: UCB HSCT
  • Drug: Tacrolimus
  • Drug: Mycophenolate mofetil (MMF)
  • Drug: G-CSF
  • Drug: Fludarabine

Study ID

Medical College of Wisconsin -- BMTCTN1502

Status

Recruiting

Trial ID

NCT02918292

Study Type

Interventional

Trial Phase

Phase 2

Enrollment Quota

60

Sponsor

Medical College of Wisconsin

Inclusion Criteria

    1. Patient is < 75 years of age at time of enrollment. 2. Confirmed diagnosis of SAA, either from initial diagnosis or follow-up assessments, defined as: 1. Bone marrow cellularity < 25% or marrow cellularity < 50% but with < 30% residual hematopoietic cells. 2. Two out of three of the following (in peripheral blood): Neutrophils < 0.5 x10^9/L, Platelets < 20 x10^9/L, or Reticulocyte count < 20 x10^9/L 3. No suitable fully matched related (6/6 match for human leukocyte antigen (HLA)-A and B at intermediate or high resolution and DRB1 at high resolution using DNA-based typing) or unrelated donor (8/8 match for HLA-A, B, C, and DRB1 at high resolution using DNA-based typing) available. Search for an unrelated donor and enrollment on this protocol may be abandoned if the clinical situation dictates an urgent transplant in the best medical judgment of the treating provider. The definition of clinical urgency may include a low likelihood of identifying a suitable matched unrelated donor within 6-8 weeks from referral and the medical need to choose a donor without further delay beyond that time. 4. Failed at least one trial of immunosuppressive therapy (IST) by being refractory or having relapsed. IST could have included ATG based regimens, calcineurin inhibitors and/or other higher dose therapy directed at the treatment of primary SAA. 5. Available alternative donor: 1. Cord blood unit(s) must be matched at a minimum of 4/6 to the recipient at HLA-A and B at low resolution using DNA-based typing and HLA-DRB1 at high resolution using DNA-based typing. Based on a published report from Eurocord, for single unit transplantation, the single unit pre-cryopreserved total nucleated cell (TNC) dose must be a minimum of 4.0 x10^7/kg recipient weight. For double cord transplants, each unit must have a minimum of 1.5 x10^7/kg pre-cryopreserved TNC and a minimum total of 4.0 x10^7/kg (sum of unit 1 and unit 2). For non-red blood cell depleted units, the minimum pre-cryopreserved TNC dose is 2.0 x10^7/kg recipient weight. or 2. HLA haplo first degree relatives of the patient including biological parents, siblings or half siblings, or children with 2, 3, or 4 mismatches using DNA-based typing. A unidirectional mismatch in either the graft versus host or host versus graft direction is considered a mismatch. The donor and recipient must be identical at a minimum of one allele (at high resolution DNA-based typing) at the following genetic loci: HLA-A, -B, -C, and DRB1. 6. Patient and/or legal guardian must sign informed consent for HSCT. 7. In the haplo cohort, the donor and/or legal guardian must be able to sign informed consent documents. 8. In the haplo cohort, the potential donor must be willing to donate bone marrow. 9. In the haplo cohort, the weight of the haplo donor must be ? 20 kg. 10. Adequate organ function defined as: 1. Cardiac: Left ventricular ejection fraction (LVEF) at rest ? 40%. For patients aged < 13 years, shortening fraction (SF) ? 26% by echocardiogram or Multi Gated Acquisition Scan (MUGA) may be substituted for LVEF. 2. Hepatic: Total bilirubin < 3.0 x the upper limit of normal (ULN) for age (patients who have been diagnosed with Gilbert's Disease are allowed to exceed this limit) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5.0 x ULN for age. 3. Renal: For patients > 13.0 years of age at the time of enrollment: estimated creatinine clearance > 50 mL/minute (using the Cockcroft-Gault formula and actual body weight). For patients < 13.0 years of age at enrollment: Glomerular Filtration Rate (GFR) estimated by the updated Schwartz formula ? 90 mL/min/1.73 m2. If the estimated GFR is < 90 mL/min/1.73 m^2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be > 50 mL/min/1.73 m^2. 4. Pulmonary: For patients > 13.0 years of age: Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected/adjusted for hemoglobin) > 40% and forced expiratory volume in one second (FEV1) > 50% predicted (without administration of bronchodilator) and forced vital capacity (FVC) > 50% predicted. For patients < 13.0 years of age unable to perform pulmonary function tests (PFT) due to age or developmental ability: (1) no evidence of dyspnea at rest and (2) no need for supplemental oxygen and (3) O2 saturation > 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care (e.g., Utah, 4,200 feet above sea level, does not give supplemental oxygen unless below 90%)). 11. Karnofsky or Lansky performance status ? 60%. 12. Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time or agree to abstinence.

Exclusion Criteria

    1. Inherited bone marrow failure syndromes. At minimum, the diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow. 2. Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (e.g. Monosomy 7). 3. Presence of anti-donor HLA antibodies (positive anti-donor HLA antibody is defined as a positive cross-match test of any titer by complement-dependent cytotoxicity or flow cytometric testing or the presence of anti-donor HLA antibody to the high expression loci HLA-A, B, C, DRB1, or DPB1 with mean fluorescence intensity (MFI) > 1000 by solid phase immunoassay). 4. Prior allogeneic stem cell transplant. 5. Prior solid organ transplant. 6. Known life-threatening reaction (i.e., anaphylaxis) to Thymoglobulin® that would prohibit use for the patient as this study requires use of the Thymoglobulin® preparation of ATG. 7. Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical treatment. 8. Seropositive for the human immunodeficiency virus (HIV). 9. Active Hepatitis B or C determined by a detectable viral load of HBV or HCV. 10. Female patients who are pregnant (per institutional practice) or breast-feeding. 11. Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent > 5 years previously will be allowed. Cancer treated with curative intent ? 5 years previously will not be allowed unless approved by the Protocol Chairs and/or Protocol Officer. 12. Alemtuzumab or ATG within 2 weeks of enrollment.

Gender

All

Ages

75 Years and younger

Accepts Healthy Volunteers

No

Study Locations and Contact Information (112)

Study Location Distance Name Phone Email
Dana Faber Cancer InstituteBrigham Womens - Boston, Massachusetts 2.6 miles Joseph Antin MD None jantin@partners.org
Dana Faber Cancer InstituteBrigham Womens - Boston, Massachusetts 2.6 miles Joseph Antin MD None jantin@partners.org
Dana Faber Cancer InstituteBrigham Womens - Boston, Massachusetts 2.6 miles Joseph Antin MD None jantin@partners.org
Dana Faber Cancer InstituteBrigham Womens - Boston, Massachusetts 2.6 miles Joseph Antin MD None jantin@partners.org
Cohen Childrens Medical Center of New York - New Hyde Park, New York 174.3 miles Indira Sahdev MD None isahdev@nshs.edu
Cohen Childrens Medical Center of New York - New Hyde Park, New York 174.3 miles Indira Sahdev MD None isahdev@nshs.edu
Cohen Childrens Medical Center of New York - New Hyde Park, New York 174.3 miles Indira Sahdev MD None isahdev@nshs.edu
Cohen Childrens Medical Center of New York - New Hyde Park, New York 174.3 miles Indira Sahdev MD None isahdev@nshs.edu
Hackensack University Medical Center - Hackensack, New Jersey 183.7 miles Alfred Gillio MD None agillio@Hackensack.umc.org
Hackensack University Medical Center - Hackensack, New Jersey 183.7 miles Alfred Gillio MD None agillio@Hackensack.umc.org
Hackensack University Medical Center - Hackensack, New Jersey 183.7 miles Alfred Gillio MD None agillio@Hackensack.umc.org
Hackensack University Medical Center - Hackensack, New Jersey 183.7 miles Alfred Gillio MD None agillio@Hackensack.umc.org
University of Pennsylvania Cancer Center - Philadelphia, Pennsylvania 270.8 miles Edward Stadtmauer MD None edward.stadtmauer@uphs.upenn.edu
University of Pennsylvania Cancer Center - Philadelphia, Pennsylvania 270.8 miles Edward Stadtmauer MD None edward.stadtmauer@uphs.upenn.edu
University of Pennsylvania Cancer Center - Philadelphia, Pennsylvania 270.8 miles Edward Stadtmauer MD None edward.stadtmauer@uphs.upenn.edu
University of Pennsylvania Cancer Center - Philadelphia, Pennsylvania 270.8 miles Edward Stadtmauer MD None edward.stadtmauer@uphs.upenn.edu
Penn State College of MedicineThe Milton S Hershey Medical Center - Hershey, Pennsylvania 321.7 miles Robert Greiner MD None rgreiner1@hmc.psu.edu
Penn State College of MedicineThe Milton S Hershey Medical Center - Hershey, Pennsylvania 321.7 miles Robert Greiner MD None rgreiner1@hmc.psu.edu
Penn State College of MedicineThe Milton S Hershey Medical Center - Hershey, Pennsylvania 321.7 miles Robert Greiner MD None rgreiner1@hmc.psu.edu
Penn State College of MedicineThe Milton S Hershey Medical Center - Hershey, Pennsylvania 321.7 miles Robert Greiner MD None rgreiner1@hmc.psu.edu
University of Rochester - Rochester, New York 335.8 miles Jeffery Andolina MD None jeffrey_andolina@urmc.rochester.edu
University of Rochester - Rochester, New York 335.8 miles Jeffery Andolina MD None jeffrey_andolina@urmc.rochester.edu
University of Rochester - Rochester, New York 335.8 miles Jeffery Andolina MD None jeffrey_andolina@urmc.rochester.edu
University of Rochester - Rochester, New York 335.8 miles Jeffery Andolina MD None jeffrey_andolina@urmc.rochester.edu
Johns Hopkins Unversity - Baltimore, Maryland 357.9 miles Aleksandra Petrovic MD None apetrov@jhmi.edu
Johns Hopkins Unversity - Baltimore, Maryland 357.9 miles Aleksandra Petrovic MD None apetrov@jhmi.edu
Johns Hopkins Unversity - Baltimore, Maryland 357.9 miles Aleksandra Petrovic MD None apetrov@jhmi.edu
Johns Hopkins Unversity - Baltimore, Maryland 357.9 miles Aleksandra Petrovic MD None apetrov@jhmi.edu
Childrens National Medical Center - Washington, D.C., District of Columbia 391.7 miles Davila Saldana MD None BJDAVILAS1@childrensnational.org
Childrens National Medical Center - Washington, D.C., District of Columbia 391.7 miles Davila Saldana MD None BJDAVILAS1@childrensnational.org
Childrens National Medical Center - Washington, D.C., District of Columbia 391.7 miles Davila Saldana MD None BJDAVILAS1@childrensnational.org
Childrens National Medical Center - Washington, D.C., District of Columbia 391.7 miles Davila Saldana MD None BJDAVILAS1@childrensnational.org
Roswell Park Cancer Institute - Buffalo, New York 397.2 miles Barbara Bambach MD None barb.bambach@roswellpark.org
Roswell Park Cancer Institute - Buffalo, New York 397.2 miles Barbara Bambach MD None barb.bambach@roswellpark.org
Roswell Park Cancer Institute - Buffalo, New York 397.2 miles Barbara Bambach MD None barb.bambach@roswellpark.org
Roswell Park Cancer Institute - Buffalo, New York 397.2 miles Barbara Bambach MD None barb.bambach@roswellpark.org
Virginia Commonwealth University - Richmond, Virginia 473.4 miles Christina Wiedl MD None Cwiedl@mcvh-Vcu.edu
Virginia Commonwealth University - Richmond, Virginia 473.4 miles Christina Wiedl MD None Cwiedl@mcvh-Vcu.edu
Virginia Commonwealth University - Richmond, Virginia 473.4 miles Christina Wiedl MD None Cwiedl@mcvh-Vcu.edu
Virginia Commonwealth University - Richmond, Virginia 473.4 miles Christina Wiedl MD None Cwiedl@mcvh-Vcu.edu
Duke University Medical Center - Durham, North Carolina 608.4 miles Joanne Kurtzberg MD None Kurtz001@mc.duke.edu
Duke University Medical Center - Durham, North Carolina 608.4 miles Joanne Kurtzberg MD None Kurtz001@mc.duke.edu
Duke University Medical Center - Durham, North Carolina 608.4 miles Joanne Kurtzberg MD None Kurtz001@mc.duke.edu
Duke University Medical Center - Durham, North Carolina 608.4 miles Joanne Kurtzberg MD None Kurtz001@mc.duke.edu
Karmanos Cancer InstituteChildrens Hospital of Michigan - Detroit, Michigan 611.5 miles Sureyya Savasan MD None ssavasan@med.wayne.edu
Karmanos Cancer InstituteChildrens Hospital of Michigan - Detroit, Michigan 611.5 miles Sureyya Savasan MD None ssavasan@med.wayne.edu
Karmanos Cancer InstituteChildrens Hospital of Michigan - Detroit, Michigan 611.5 miles Sureyya Savasan MD None ssavasan@med.wayne.edu
Karmanos Cancer InstituteChildrens Hospital of Michigan - Detroit, Michigan 611.5 miles Sureyya Savasan MD None ssavasan@med.wayne.edu
Indiana University Medical Center Riley Hospital for Children - Indianapolis, Indiana 805.0 miles David Delgado MD None dcdelgad@iu.edu
Indiana University Medical Center Riley Hospital for Children - Indianapolis, Indiana 805.0 miles David Delgado MD None dcdelgad@iu.edu
Indiana University Medical Center Riley Hospital for Children - Indianapolis, Indiana 805.0 miles David Delgado MD None dcdelgad@iu.edu
Indiana University Medical Center Riley Hospital for Children - Indianapolis, Indiana 805.0 miles David Delgado MD None dcdelgad@iu.edu
University of LouisvilleKosair Childrens Hospital - Louisville, Kentucky 823.2 miles Alexandra Cheerva MD None a.cheerva@louisville.edu
University of LouisvilleKosair Childrens Hospital - Louisville, Kentucky 823.2 miles Alexandra Cheerva MD None a.cheerva@louisville.edu
University of LouisvilleKosair Childrens Hospital - Louisville, Kentucky 823.2 miles Alexandra Cheerva MD None a.cheerva@louisville.edu
University of LouisvilleKosair Childrens Hospital - Louisville, Kentucky 823.2 miles Alexandra Cheerva MD None a.cheerva@louisville.edu
Childrens Hospital of WisconsinMidwest Childrens Cancer - Milwaukee, Wisconsin 854.1 miles Julie Talano MD None jtalano@mcw.edu
Childrens Hospital of WisconsinMidwest Childrens Cancer - Milwaukee, Wisconsin 854.1 miles Julie Talano MD None jtalano@mcw.edu
Childrens Hospital of WisconsinMidwest Childrens Cancer - Milwaukee, Wisconsin 854.1 miles Julie Talano MD None jtalano@mcw.edu
Childrens Hospital of WisconsinMidwest Childrens Cancer - Milwaukee, Wisconsin 854.1 miles Julie Talano MD None jtalano@mcw.edu
Northside Hospital - Atlanta, Georgia 929.9 miles Melhem Solh MD None None
Northside Hospital - Atlanta, Georgia 929.9 miles Melhem Solh MD None None
Northside Hospital - Atlanta, Georgia 929.9 miles Melhem Solh MD None None
Northside Hospital - Atlanta, Georgia 929.9 miles Melhem Solh MD None None
Cardinal Glennon Childrens Medical Center - Saint Louis, Missouri 1,039.5 miles William Ferguson MD None fergusws@slu.edu
Cardinal Glennon Childrens Medical Center - Saint Louis, Missouri 1,039.5 miles William Ferguson MD None fergusws@slu.edu
Cardinal Glennon Childrens Medical Center - Saint Louis, Missouri 1,039.5 miles William Ferguson MD None fergusws@slu.edu
Cardinal Glennon Childrens Medical Center - Saint Louis, Missouri 1,039.5 miles William Ferguson MD None fergusws@slu.edu
University of Florida College of Medicine - Gainesville, Florida 1,081.3 miles John Wingard MD None wingajr@medicine.ufl.edu
University of Florida College of Medicine - Gainesville, Florida 1,081.3 miles John Wingard MD None wingajr@medicine.ufl.edu
University of Florida College of Medicine - Gainesville, Florida 1,081.3 miles John Wingard MD None wingajr@medicine.ufl.edu
University of Florida College of Medicine - Gainesville, Florida 1,081.3 miles John Wingard MD None wingajr@medicine.ufl.edu
University of Minnesota - Minneapolis, Minnesota 1,120.0 miles Jakub Tolar MD None tolar003@umn.edu
University of Minnesota - Minneapolis, Minnesota 1,120.0 miles Jakub Tolar MD None tolar003@umn.edu
University of Minnesota - Minneapolis, Minnesota 1,120.0 miles Jakub Tolar MD None tolar003@umn.edu
University of Minnesota - Minneapolis, Minnesota 1,120.0 miles Jakub Tolar MD None tolar003@umn.edu
H Lee Moffitt Cancer Center - Tampa, Florida 1,179.8 miles Claudio Anasetti MD None claudio.anasetti@moffitt.org
H Lee Moffitt Cancer Center - Tampa, Florida 1,179.8 miles Claudio Anasetti MD None claudio.anasetti@moffitt.org
H Lee Moffitt Cancer Center - Tampa, Florida 1,179.8 miles Claudio Anasetti MD None claudio.anasetti@moffitt.org
H Lee Moffitt Cancer Center - Tampa, Florida 1,179.8 miles Claudio Anasetti MD None claudio.anasetti@moffitt.org
Childrens Mercy Hospital and Clinics - Kansas City, Missouri 1,249.3 miles Mohamed Radhi MD None maradhi@cmh.edu
Childrens Mercy Hospital and Clinics - Kansas City, Missouri 1,249.3 miles Mohamed Radhi MD None maradhi@cmh.edu
Childrens Mercy Hospital and Clinics - Kansas City, Missouri 1,249.3 miles Mohamed Radhi MD None maradhi@cmh.edu
Childrens Mercy Hospital and Clinics - Kansas City, Missouri 1,249.3 miles Mohamed Radhi MD None maradhi@cmh.edu
Miami Childrens Hospital - Miami, Florida 1,265.3 miles Kamar Godder MD None kamar.godder@mch.com
Miami Childrens Hospital - Miami, Florida 1,265.3 miles Kamar Godder MD None kamar.godder@mch.com
Miami Childrens Hospital - Miami, Florida 1,265.3 miles Kamar Godder MD None kamar.godder@mch.com
Miami Childrens Hospital - Miami, Florida 1,265.3 miles Kamar Godder MD None kamar.godder@mch.com
Baylor College of MedicineThe Methodist Hospital - Houston, Texas 1,609.9 miles Helen Heslop MD None HeHeslop@texaschildrenshospital.org
University of TexasMD Anderson Cancer Center - Houston, Texas 1,609.9 miles Amin Alousi MD None aalousi@mdanderson.org
Baylor College of MedicineThe Methodist Hospital - Houston, Texas 1,609.9 miles Helen Heslop MD None HeHeslop@texaschildrenshospital.org
University of TexasMD Anderson Cancer Center - Houston, Texas 1,609.9 miles Amin Alousi MD None aalousi@mdanderson.org
Baylor College of MedicineThe Methodist Hospital - Houston, Texas 1,609.9 miles Helen Heslop MD None HeHeslop@texaschildrenshospital.org
University of TexasMD Anderson Cancer Center - Houston, Texas 1,609.9 miles Amin Alousi MD None aalousi@mdanderson.org
Baylor College of MedicineThe Methodist Hospital - Houston, Texas 1,609.9 miles Helen Heslop MD None HeHeslop@texaschildrenshospital.org
University of TexasMD Anderson Cancer Center - Houston, Texas 1,609.9 miles Amin Alousi MD None aalousi@mdanderson.org
City of Hope National Medical Center - Duarte, California 2,578.2 miles Anna Pawlowska MD None apawlowska@coh.org
City of Hope National Medical Center - Duarte, California 2,578.2 miles Anna Pawlowska MD None apawlowska@coh.org
City of Hope National Medical Center - Duarte, California 2,578.2 miles Anna Pawlowska MD None apawlowska@coh.org
City of Hope National Medical Center - Duarte, California 2,578.2 miles Anna Pawlowska MD None apawlowska@coh.org
Childrens Hospital of Los Angeles - Los Angeles, California 2,595.3 miles Michael Pulsipher MD None mpulsipher@chla.usc.edu
Childrens Hospital of Los Angeles - Los Angeles, California 2,595.3 miles Michael Pulsipher MD None mpulsipher@chla.usc.edu
Childrens Hospital of Los Angeles - Los Angeles, California 2,595.3 miles Michael Pulsipher MD None mpulsipher@chla.usc.edu
Childrens Hospital of Los Angeles - Los Angeles, California 2,595.3 miles Michael Pulsipher MD None mpulsipher@chla.usc.edu
Childrens Hospital at Oakland - Oakland, California 2,688.0 miles Mark Walters MD None mwalters@mail.cho.org
Childrens Hospital at Oakland - Oakland, California 2,688.0 miles Mark Walters MD None mwalters@mail.cho.org
Childrens Hospital at Oakland - Oakland, California 2,688.0 miles Mark Walters MD None mwalters@mail.cho.org
Childrens Hospital at Oakland - Oakland, California 2,688.0 miles Mark Walters MD None mwalters@mail.cho.org
Stanford Hospital and Clinics - Stanford, California 2,694.5 miles Sally Arai MD None sarai1@stanford.edu
Stanford Hospital and Clinics - Stanford, California 2,694.5 miles Sally Arai MD None sarai1@stanford.edu
Stanford Hospital and Clinics - Stanford, California 2,694.5 miles Sally Arai MD None sarai1@stanford.edu
Stanford Hospital and Clinics - Stanford, California 2,694.5 miles Sally Arai MD None sarai1@stanford.edu

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