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T Cell Receptor α/β TCD HCT in Patients With Fanconi Anemia

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ClinicalTrials.gov Identifier: NCT03579875
Recruitment Status : Recruiting
First Posted : July 9, 2018
Last Update Posted : May 24, 2021
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE May 25, 2018
First Posted Date  ICMJE July 9, 2018
Last Update Posted Date May 24, 2021
Actual Study Start Date  ICMJE November 13, 2018
Estimated Primary Completion Date February 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 26, 2018)
Grade II-IV acute graft versus host disease (GVHD) [ Time Frame: Day 100 ]
incidence of grade II-IV acute graft versus host disease (GVHD)
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2018)
  • Neutrophil engraftment [ Time Frame: Day 42 ]
    Rate of neutrophil engraftment (defined as the first of three consecutive days after HCT that the patient's absolute neutrophil counts is ≥ 0.5x109 per liter)
  • Platelet engraftment [ Time Frame: Day 42 ]
    Time to platelet engraftment (First of three consecutive days after HCT that the patient's platelet count ≥ 20x10^9 per liter)
  • Acute graft versus host disease (aGVHD) [ Time Frame: Day 100 ]
    Incidence of grade III-IV acute graft versus host disease
  • Chronic graft versus host disease (cGVHD) [ Time Frame: 1 Year after transplant ]
    Incidence of chronic graft versus host disease after transplant
  • Regimen related toxicity [ Time Frame: 30 Days after transplant ]
    Incidence of regimen related toxicity based on CTCAE v5
  • Bacterial, viral and fungal infections [ Time Frame: 1 Year after transplant ]
    Incidence of bacterial, viral and fungal infections
  • Opportunistic infections [ Time Frame: 100 Days after transplant ]
    Incidence of opportunistic infections
  • Overall survival (OS) [ Time Frame: 1 Year after transplant ]
    Incidence of overall survival
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE T Cell Receptor α/β TCD HCT in Patients With Fanconi Anemia
Official Title  ICMJE T Cell Receptor Alpha/Beta T Cell Depleted (α/β TCD) Hematopoietic Cell Transplantation in Patients With Fanconi Anemia (FA)
Brief Summary This is a phase II trial of T cell receptor alpha/beta depletion (α/β TCD) hematopoietic cell transplantation (HCT) transplantation in patients with Fanconi anemia (FA) to eliminate the need for routine graft-versus-host disease (GVHD) immune suppression leading to earlier immune recovery and potentially a reduction in the risk of severe infections after transplantation.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Fanconi Anemia
  • Severe Aplastic Anemia
  • Myelodysplastic Syndromes
Intervention  ICMJE
  • Drug: Total Body Irradiation (TBI) (Plan 1)
    300 cGy with thymic shielding on day -6
    Other Name: TBI
  • Drug: Cyclophosphamide (CY) (Plan 1)
    10 mg/kg IV daily on days -5, -4, -3, and -2
    Other Name: CY
  • Drug: Fludarabine (FLU)
    35 mg/m2 IV daily on days -5, -4, -3, and -2
    Other Name: FLU
  • Drug: Methylprednisolone (MP)
    1 mg/kg IV q12h on days -5, -4, -3, -2, and -1
    Other Name: MP
  • Device: Donor mobilized PBSC infusion
    T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation on day 0
    Other Name: PBSC
  • Drug: G-CSF
    Initiate G-CSF 5mcg/kg per day IV on day +1 (continue until ANC >2.5 x 10^9/L for 3 consecutive days)
  • Drug: Cyclophosphamide (CY) (Plan 2)
    5 mg/kg IV daily on days -5, -4, -3, and -2
    Other Name: CY
  • Drug: Rituximab
    200 mg/m2 IV once on day -1
  • Drug: Busulfan
    Busulfan 0.6 mg/kg if > 4 years old and/or >12 kg (0.8 mg/kg IV if ≤ 4 years old and/or ≤ 12 kg) is given IV over 2 hours every 12 hours for 2 days.
    Other Name: BU
Study Arms  ICMJE
  • Experimental: Treatment Plan 1: TBI 300 with Thymic Shielding, CY, FLU, MP

    Given to:

    • Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type OR
    • Patients with an HLA- identical sibling donor recipient and MDS or acute leukemia
    Interventions:
    • Drug: Total Body Irradiation (TBI) (Plan 1)
    • Drug: Cyclophosphamide (CY) (Plan 1)
    • Drug: Fludarabine (FLU)
    • Drug: Methylprednisolone (MP)
    • Device: Donor mobilized PBSC infusion
    • Drug: G-CSF
    • Drug: Rituximab
  • Experimental: Treatment Plan 2: CY, FLU and MP

    Given to:

    • HLA-identical sibling donor recipients with aplastic anemia

    Interventions:
    • Drug: Fludarabine (FLU)
    • Drug: Methylprednisolone (MP)
    • Device: Donor mobilized PBSC infusion
    • Drug: G-CSF
    • Drug: Cyclophosphamide (CY) (Plan 2)
    • Drug: Rituximab
  • Experimental: Treatment Plan 3: BU, Cy, FLU, MP and Rituximab

    Given to:

    • Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type who cannot tolerate TBI
    • Patients with an HLA- identical sibling donor recipient and MDS or acute leukemia who cannot tolerate TBI
    • Per treating physician preference
    Interventions:
    • Drug: Cyclophosphamide (CY) (Plan 1)
    • Drug: Fludarabine (FLU)
    • Drug: Methylprednisolone (MP)
    • Drug: Rituximab
    • Drug: Busulfan
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: November 26, 2018)
48
Original Enrollment  ICMJE Not Provided
Estimated Study Completion Date  ICMJE February 2029
Estimated Primary Completion Date February 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Patient Selection:

Inclusion Criteria:

  • Diagnosis of Fanconi anemia
  • Less than 65 years of age
  • Karnofsky performance status of ≥ 70% or, for children < 16 years of age, Lansky Play Score ≥ 50
  • Presence of at least one of the following risk factors:

    • Severe aplastic anemia (SAA) defined as: Aplastic anemia is defined as having at least one of the following when not receiving growth factors or transfusions:

      • platelet count <20 x 109/L
      • absolute neutrophil count of <5 x 108/L
      • hemoglobin <8 g/dL
    • Myelodysplastic syndrome (MDS) or acute leukemia
    • High risk genotype
  • Adequate organ function defined as:

    • Bilirubin, AST or ALT, ALP <5 x normal, Cardiac: left ventricle ejection fraction (LEFV) ≥45% by ECHO
    • Pulmonary: DLCO, FEV1, FVC ≥ 40% predicted, and absence of O2 requirements. For children that are not able to cooperate with PFTs, a pulse oximetry with exercise should be attempted. If neither test can be obtained it should be clearly stated in the physician's note.
  • Identification of a suitable donor for peripheral blood cells per match criteria found in Section 5.
  • Females of childbearing potential and males with partners of child-bearing potential must agree to use of contraception for the duration of treatment and 4 months after the transplant
  • Able to provide written voluntary consent prior to the performance of any research related tests or procedures with parental/guardian consent for minor (and assent as appropriate)

Exclusion Criteria:

  • Pregnant or breastfeeding as the treatment used in this study are Pregnancy Category D. Females of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days of study registration
  • Active, uncontrolled infection within 1 week prior to starting study therapy
  • Malignant solid tumor cancer within previous 2 years

Donor Selection (Inclusion Criteria): meets one of the following match criteria:

  • an HLA-A, B, DRB1 matched sibling donor (matched sibling)
  • an HLA-A, B, DRB1 matched related donor (other than sibling)
  • a related donor mismatched at 1 HLA-A, B, C and DRB1 antigen
  • 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated donor per current institutional guidelines Patients and donors are typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing. If a donor has been selected on the basis of HLA-A, B, C and DRB1 typing as above, preference will be made for donors matched at the HLA-C locus.
  • Body weight of at least 40 kilograms and at least 12 years of age
  • Willing and able to undergo mobilized peripheral blood apheresis
  • In general good health as determined by the medical provider
  • Adequate organ function defined as:

    • Hematologic: hemoglobin, WBC, platelet within 10% of upper and lower limit of normal range of test (gender based for hemoglobin)
    • Hepatic: ALT < 2 x upper limit of normal
    • Renal: serum creatinine < 1.8 mg/dl
  • Performance of a donor infectious disease screen panel including CMV Antibody, Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis C Antibody, HIV 1/2 Antibody, HTLVA 1/2 Antibody, Treponema, and Trypanosoma Cruzi (T. Cruzi) plus HBV, HCV, WNV, HIV by nucleic acid testing (NAT); and screening for evidence of and risks factors for infection with Zika virus, or per current standard institutional donor screen - must be negative for HIV and active hepatitis B
  • Not pregnant - females of childbearing potential must have a negative pregnancy test within 7 days of mobilization start
  • Voluntary written consent (parent/guardian and minor assent, if < 18 years) prior to the performance of any research related procedure
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lisa Burke, RN 612-273-8482 lburke3@Fairview.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03579875
Other Study ID Numbers  ICMJE 2016LS161
MT2017-17 ( Other Identifier: Masonic Cancer Center, University of Minnesota )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Margaret MacMillan, MD, Msc, FRCPC Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date May 2021

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