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NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia

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ClinicalTrials.gov Identifier: NCT02833805
Recruitment Status : Recruiting
First Posted : July 14, 2016
Last Update Posted : July 18, 2019
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE July 12, 2016
First Posted Date  ICMJE July 14, 2016
Last Update Posted Date July 18, 2019
Actual Study Start Date  ICMJE September 2016
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2016)
Overall survival and engraftment at one year [ Time Frame: 1 year ]
Percentage of enrolled participants who receive BMT, achieve engraftment, and are alive at one year post BMT.
Original Primary Outcome Measures  ICMJE
 (submitted: July 13, 2016)
Overall survival at one year after BMT [ Time Frame: 1 year ]
Percentage of participants alive at one year after BMT.
Change History Complete list of historical versions of study NCT02833805 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2016)
  • Overall survival at one year [ Time Frame: 1 year ]
    Percentage of participants alive at one year after BMT.
  • Probability of neutrophil recovery [ Time Frame: 1 year ]
    Percentage of participants who have recovered neutrophil counts at 1 year.
  • Probability of platelet recovery [ Time Frame: 1 year ]
    Percentage of participants who have recovered platelet counts at 1 year.
  • Incidence of primary graft failure [ Time Frame: 1 year ]
    Percentage of participants who experience primary graft failure by one year after BMT.
  • Incidence of secondary graft failure [ Time Frame: 1 year ]
    Percentage of participants who experience secondary graft failure by one year after BMT.
  • Incidence of grades II-IV acute GVHD, Day 100 [ Time Frame: Day 100 ]
    Percentage of participants who experience grade II, III, or IV acute GVHD by Day 100.
  • Incidence of grades III-IV acute GVHD, Day 100 [ Time Frame: 1 year ]
    Percentage of participants who experience grade III or IV acute GVHD by Day 100.
  • Incidence of chronic GVHD, one year [ Time Frame: 1 year ]
    Percentage of participants who experience chronic GVHD by one year after BMT.
  • Estimate full donor chimerism [ Time Frame: Day 60 ]
    Percentage of participants with full donor chimerism at Day 60.
  • Estimate GVHD-free relapse-free survival (GRFS) [ Time Frame: 1 year ]
    Percentage of participants alive, without relapse, and without GVHD at 1 year.
  • Estimate transplant-related mortality [ Time Frame: 1 year ]
    Percentage of participants deceased for reasons related to BMT at 1 year.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2016)
  • Probability of engraftment at one year [ Time Frame: 1 year ]
    Percentage of participants alive and engrafted (i.e. without graft failure) at one year after BMT.
  • Probability of neutrophil recovery at Day 56 [ Time Frame: Day 56 ]
    Percentage of participants who have recovered neutrophil counts at Day 56.
  • Probability of platelet recovery at Day 100 [ Time Frame: Day 100 ]
    Percentage of participants who have recovered platelet counts at Day 100.
  • Incidence of primary graft failure [ Time Frame: 1 year ]
    Percentage of participants who experience primary graft failure by one year after BMT.
  • Incidence of secondary graft failure [ Time Frame: 1 year ]
    Percentage of participants who experience secondary graft failure by one year after BMT.
  • Incidence of grades II-IV acute GVHD, Day 100 [ Time Frame: Day 100 ]
    Percentage of participants who experience grade II, III, or IV acute GVHD by Day 100.
  • Incidence of grades III-IV acute GVHD, Day 100 [ Time Frame: 1 year ]
    Percentage of participants who experience grade III or IV acute GVHD by Day 100.
  • Incidence of chronic GVHD, one year [ Time Frame: 1 year ]
    Percentage of participants who experience chronic GVHD by one year after BMT.
  • Immune reconstitution in first year after BMT [ Time Frame: 1 year ]
    Characterize the pace and quality of immune reconstitution at 3, 6, and 12 months after BMT.
  • Infectious complications in first year after BMT [ Time Frame: 1 year ]
    Monitor targeted infections complications (CMV, EBV, and PTLD) in the first year after BMT.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia
Official Title  ICMJE A Phase II Trial of Non-Myeloablative (NMA) Conditioning and Transplantation of Partially HLA-Mismatched/Haploidentical Related or Matched Unrelated Donor (MUD) Bone Marrow for Newly Diagnosed Patients With Severe Aplastic Anemia
Brief Summary Our primary objective is to determine if it is feasible for previously untreated severe aplastic anemia (SAA) patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide.
Detailed Description This is a clinical trial of upfront bone marrow transplantation for patients with SAA who do not have a fully human leukocyte antigen (HLA) matched donor. The trial uses a conditioning regimen which has been successful in the refractory and relapsed setting to maximize engraftment and post transplant therapy to minimize graft versus host disease (GVHD). This would be used here in patients who have not yet undergone immunosuppressive therapy for their SAA or are thought to be unlikely to respond to immunosuppressive therapy for SAA.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Severe Aplastic Anemia
  • Aplastic Anemia
  • Bone Marrow Failure
  • Immunosuppression
Intervention  ICMJE
  • Drug: Thymoglobulin
    Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily
    Other Names:
    • Anti-thymocyte globulin
    • ATG
  • Drug: Fludarabine
    Days -6 through -2: 30 mg/m^2 IV daily
    Other Name: Fludara
  • Drug: Cyclophosphamide
    Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily
    Other Names:
    • Cytoxan
    • Cy
    • CTX
  • Radiation: Total body irradiation
    Day -1: 200 centigray (cGy) in a single fraction
    Other Name: TBI
  • Drug: Tacrolimus
    Start on Day 5 through Day 365
    Other Names:
    • FK-506
    • FK506
    • Prograf
  • Drug: Mycophenolate mofetil
    Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
    Other Names:
    • MMF
    • CellCept
Study Arms  ICMJE Experimental: Bone marrow transplant
Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis.
Interventions:
  • Drug: Thymoglobulin
  • Drug: Fludarabine
  • Drug: Cyclophosphamide
  • Radiation: Total body irradiation
  • Drug: Tacrolimus
  • Drug: Mycophenolate mofetil
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 13, 2016)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2020
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Confirmed diagnosis of inherited or acquired severe aplastic anemia (SAA)
  • One of the following available donors:

    1. HLA-haploidentical relative
    2. If recipient is >= 40 years old, may use HLA-matched related donor
    3. For recipients with inherited bone marrow failure syndromes (IBMFS) with clear evidence of same disorder in potential related donors, may use 10/10 matched unrelated donor
  • Recipient and/or legal guardian must sign protocol informed consent
  • Donor must be willing to donate bone marrow
  • Left ventricular ejection fraction (LVEF) >= 40%. For recipients < 13 years old, shortening fraction >= 26% may be used instead.
  • Bilirubin < 3 x upper limit of normal (ULN) for age, unless patient has Gilbert's disease
  • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN for age
  • For patients >= 13 years old: estimated creatinine clearance > 50 mL/min using Cockcroft-Gault formula and actual body weight
  • For patients >= 1 but < 13 years old: glomerular filtration rate (GFR) estimated by updated Schwartz formula >= 90 mL/min/1.73 m^2. If estimated GFR is < 90 mL/min/1.73 m^2, 24-hour measured creatinine clearance must be > 50 mL/min/1.73 m^2.
  • For patients >= 8 years old, diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) > 40%; forced expiratory volume at one second (FEV1) > 50%; forced vital capacity (FVC) > 50%
  • For patients < 8 years old or unable to undergo pulmonary function testing: no evidence of dyspnea at rest; no need for supplemental oxygen; oxygen saturation > 92% on room air
  • Karnofsky/Lansky status (depending on age) >= 70%
  • Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time. If unwilling, they must agree to complete abstinence.

Exclusion Criteria:

  • Previous administration of immunosuppressive therapy for SAA.
  • Fanconi anemia. At minimum, this diagnosis must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow in patients < 30 years old.
  • Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on bone marrow examination
  • Presence of anti-donor antibodies
  • Prior allogeneic stem cell transplant
  • Prior solid organ transplant
  • Uncontrolled bacterial, viral, or fungal infection
  • HIV seropositivity
  • Active hepatitis B or C infection determined by serology and/or nucleic acid testing (NAT)
  • Pregnancy or active breastfeeding
  • Prior malignancies except: resected basal carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent > 5 years previously. Other prior cancers will not be allowed unless approved by the PI.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amy E DeZern, MD 410-502-7208 adezern1@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02833805
Other Study ID Numbers  ICMJE J1688
IRB00107139 ( Other Identifier: JHMIRB )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Amy E DeZern, MD Johns Hopkins University
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP