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

Primary Purpose

Fanconi Anemia, Severe Aplastic Anemia, Myelodysplastic Syndromes

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Total Body Irradiation (TBI) (Plan 1)
Cyclophosphamide (CY) (Plan 1)
Fludarabine (FLU)
Methylprednisolone (MP)
Donor mobilized PBSC infusion
G-CSF
Cyclophosphamide (CY) (Plan 2)
Rituximab
Busulfan
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fanconi Anemia

Eligibility Criteria

undefined - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Masonic Cancer Center at University of MinnesotaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Treatment Plan 1: TBI 300 with Thymic Shielding, CY, FLU, MP

Treatment Plan 2: CY, FLU and MP

Treatment Plan 3: BU, Cy, FLU, MP and Rituximab

Arm Description

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

Given to: • HLA-identical sibling donor recipients with aplastic anemia

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

Outcomes

Primary Outcome Measures

Grade II-IV acute graft versus host disease (GVHD)
incidence of grade II-IV acute graft versus host disease (GVHD)

Secondary Outcome Measures

Neutrophil engraftment
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 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)
Incidence of grade III-IV acute graft versus host disease
Chronic graft versus host disease (cGVHD)
Incidence of chronic graft versus host disease after transplant
Regimen related toxicity
Incidence of regimen related toxicity based on CTCAE v5
Bacterial, viral and fungal infections
Incidence of bacterial, viral and fungal infections
Opportunistic infections
Incidence of opportunistic infections
Overall survival (OS)
Incidence of overall survival

Full Information

First Posted
May 25, 2018
Last Updated
November 2, 2022
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT03579875
Brief Title
T Cell Receptor α/β TCD HCT in Patients With Fanconi Anemia
Official Title
T Cell Receptor Alpha/Beta T Cell Depleted (α/β TCD) Hematopoietic Cell Transplantation in Patients With Fanconi Anemia (FA)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 13, 2018 (Actual)
Primary Completion Date
January 1, 2026 (Anticipated)
Study Completion Date
January 5, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fanconi Anemia, Severe Aplastic Anemia, Myelodysplastic Syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment Plan 1: TBI 300 with Thymic Shielding, CY, FLU, MP
Arm Type
Experimental
Arm Description
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
Arm Title
Treatment Plan 2: CY, FLU and MP
Arm Type
Experimental
Arm Description
Given to: • HLA-identical sibling donor recipients with aplastic anemia
Arm Title
Treatment Plan 3: BU, Cy, FLU, MP and Rituximab
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Total Body Irradiation (TBI) (Plan 1)
Other Intervention Name(s)
TBI
Intervention Description
300 cGy with thymic shielding on day -6
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide (CY) (Plan 1)
Other Intervention Name(s)
CY
Intervention Description
10 mg/kg IV daily on days -5, -4, -3, and -2
Intervention Type
Drug
Intervention Name(s)
Fludarabine (FLU)
Other Intervention Name(s)
FLU
Intervention Description
35 mg/m2 IV daily on days -5, -4, -3, and -2
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone (MP)
Other Intervention Name(s)
MP
Intervention Description
1 mg/kg IV q12h on days -5, -4, -3, -2, and -1
Intervention Type
Device
Intervention Name(s)
Donor mobilized PBSC infusion
Other Intervention Name(s)
PBSC
Intervention Description
T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation on day 0
Intervention Type
Drug
Intervention Name(s)
G-CSF
Intervention Description
Initiate G-CSF 5mcg/kg per day IV on day +1 (continue until ANC >2.5 x 10^9/L for 3 consecutive days)
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide (CY) (Plan 2)
Other Intervention Name(s)
CY
Intervention Description
5 mg/kg IV daily on days -5, -4, -3, and -2
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
200 mg/m2 IV once on day -1
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
BU
Intervention Description
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.
Primary Outcome Measure Information:
Title
Grade II-IV acute graft versus host disease (GVHD)
Description
incidence of grade II-IV acute graft versus host disease (GVHD)
Time Frame
Day 100
Secondary Outcome Measure Information:
Title
Neutrophil engraftment
Description
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)
Time Frame
Day 42
Title
Platelet engraftment
Description
Time to platelet engraftment (First of three consecutive days after HCT that the patient's platelet count ≥ 20x10^9 per liter)
Time Frame
Day 42
Title
Acute graft versus host disease (aGVHD)
Description
Incidence of grade III-IV acute graft versus host disease
Time Frame
Day 100
Title
Chronic graft versus host disease (cGVHD)
Description
Incidence of chronic graft versus host disease after transplant
Time Frame
1 Year after transplant
Title
Regimen related toxicity
Description
Incidence of regimen related toxicity based on CTCAE v5
Time Frame
30 Days after transplant
Title
Bacterial, viral and fungal infections
Description
Incidence of bacterial, viral and fungal infections
Time Frame
1 Year after transplant
Title
Opportunistic infections
Description
Incidence of opportunistic infections
Time Frame
100 Days after transplant
Title
Overall survival (OS)
Description
Incidence of overall survival
Time Frame
1 Year after transplant

10. Eligibility

Sex
All
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lisa Burke, RN
Phone
612-273-8482
Email
lburke3@Fairview.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Margaret MacMillan, MD, Msc, FRCPC
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center at University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Burke, RN
Phone
612-273-8482
Email
lburke3@Fairview.org

12. IPD Sharing Statement

Learn more about this trial

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

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