- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03579875
T Cell Receptor α/β TCD HCT in Patients With Fanconi Anemia
T Cell Receptor Alpha/Beta T Cell Depleted (α/β TCD) Hematopoietic Cell Transplantation in Patients With Fanconi Anemia (FA)
Study Overview
Status
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Lisa Burke, RN
- Phone Number: 612-273-8482
- Email: lburke3@Fairview.org
Study Locations
-
-
Minnesota
-
Minneapolis, Minnesota, United States, 55455
- Recruiting
- Masonic Cancer Center at University of Minnesota
-
Contact:
- Lisa Burke, RN
- Phone Number: 612-273-8482
- Email: lburke3@Fairview.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment Plan 1: TBI 300 with Thymic Shielding, CY, FLU, MP
Given to:
|
300 cGy with thymic shielding on day -6
Other Names:
10 mg/kg IV daily on days -5, -4, -3, and -2
Other Names:
35 mg/m2 IV daily on days -5, -4, -3, and -2
Other Names:
1 mg/kg IV q12h on days -5, -4, -3, -2, and -1
Other Names:
T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation on day 0
Other Names:
Initiate G-CSF 5mcg/kg per day IV on day +1 (continue until ANC >2.5 x 10^9/L for 3 consecutive days)
200 mg/m2 IV once on day -1
|
Experimental: Treatment Plan 2: CY, FLU and MP
Given to: • HLA-identical sibling donor recipients with aplastic anemia |
35 mg/m2 IV daily on days -5, -4, -3, and -2
Other Names:
1 mg/kg IV q12h on days -5, -4, -3, -2, and -1
Other Names:
T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation on day 0
Other Names:
Initiate G-CSF 5mcg/kg per day IV on day +1 (continue until ANC >2.5 x 10^9/L for 3 consecutive days)
200 mg/m2 IV once on day -1
5 mg/kg IV daily on days -5, -4, -3, and -2
Other Names:
|
Experimental: Treatment Plan 3: BU, Cy, FLU, MP and Rituximab
Given to:
|
10 mg/kg IV daily on days -5, -4, -3, and -2
Other Names:
35 mg/m2 IV daily on days -5, -4, -3, and -2
Other Names:
1 mg/kg IV q12h on days -5, -4, -3, -2, and -1
Other Names:
200 mg/m2 IV once on day -1
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Grade II-IV acute graft versus host disease (GVHD)
Time Frame: Day 100
|
incidence of grade II-IV acute graft versus host disease (GVHD)
|
Day 100
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
Day 42
|
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)
|
Day 42
|
Acute graft versus host disease (aGVHD)
Time Frame: Day 100
|
Incidence of grade III-IV acute graft versus host disease
|
Day 100
|
Chronic graft versus host disease (cGVHD)
Time Frame: 1 Year after transplant
|
Incidence of chronic graft versus host disease after transplant
|
1 Year after transplant
|
Regimen related toxicity
Time Frame: 30 Days after transplant
|
Incidence of regimen related toxicity based on CTCAE v5
|
30 Days after transplant
|
Bacterial, viral and fungal infections
Time Frame: 1 Year after transplant
|
Incidence of bacterial, viral and fungal infections
|
1 Year after transplant
|
Opportunistic infections
Time Frame: 100 Days after transplant
|
Incidence of opportunistic infections
|
100 Days after transplant
|
Overall survival (OS)
Time Frame: 1 Year after transplant
|
Incidence of overall survival
|
1 Year after transplant
|
Collaborators and Investigators
Investigators
- Principal Investigator: Margaret MacMillan, MD, Msc, FRCPC, Masonic Cancer Center, University of Minnesota
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Kidney Diseases
- Urologic Diseases
- Bone Marrow Diseases
- Hematologic Diseases
- Genetic Diseases, Inborn
- DNA Repair-Deficiency Disorders
- Anemia, Hypoplastic, Congenital
- Congenital Bone Marrow Failure Syndromes
- Bone Marrow Failure Disorders
- Renal Tubular Transport, Inborn Errors
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Myelodysplastic Syndromes
- Anemia
- Fanconi Syndrome
- Fanconi Anemia
- Anemia, Aplastic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Neuroprotective Agents
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Immunological
- Methylprednisolone
- Cyclophosphamide
- Rituximab
- Fludarabine
- Busulfan
Other Study ID Numbers
- 2016LS161
- MT2017-17 (Other Identifier: Masonic Cancer Center, University of Minnesota)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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