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RECRUITINGPhase 2INTERVENTIONAL

Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders

MT2017-17:T Cell Receptor Alpha/Beta T Cell Depleted Hematopoietic Cell Transplantation in Patients With Inherited Bone Marrow Failure (BMF) Disorders

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

This is a phase II trial of T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation in patients with inherited bone marrow failure (BMF) disorders 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.

Who May Be Eligible (Plain English)

Patient Selection: Who May Qualify: For FA patients: - Diagnosis of Fanconi anemia - Age \<65 years of age - Has one of the following risk factors: - Severe aplastic anemia (SAA) - Myelodysplastic features - High risk genotype - weakened immune system associated with history of recurrent infections - Karnofsky performance status ≥ 70% if ≥ 16 years of age or Lansky play score ≥ 50% for patients \<16 years of age - Adequate pulmonary, cardiac and liver function - Voluntary written consent (minor assent if appropriate) prior to the performance of any study related procedures not part of standard medical care For TBD patients: • Diagnosis of TBD - Age \<70 years of age - Has one of the following risk factors: - Severe aplastic anemia (SAA) - Myelodysplastic features - Karnofsky performance status ≥ 70% if ≥ 16 years of age or Lansky play score ≥ 50% for patients \<16 years of age - Adequate pulmonary, cardiac and liver function - Voluntary written consent (minor assent if appropriate) prior to the performance of any study related procedures not part of standard medical care Who Should NOT Join This Trial: - 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Patient Selection: Inclusion Criteria: For FA patients: * Diagnosis of Fanconi anemia * Age \<65 years of age * Has one of the following risk factors: * Severe aplastic anemia (SAA) * Myelodysplastic features * High risk genotype * Immunodeficiency associated with history of recurrent infections * Karnofsky performance status ≥ 70% if ≥ 16 years of age or Lansky play score ≥ 50% for patients \<16 years of age * Adequate pulmonary, cardiac and liver function * Voluntary written consent (minor assent if appropriate) prior to the performance of any study related procedures not part of standard medical care For TBD patients: • Diagnosis of TBD * Age \<70 years of age * Has one of the following risk factors: * Severe aplastic anemia (SAA) * Myelodysplastic features * Karnofsky performance status ≥ 70% if ≥ 16 years of age or Lansky play score ≥ 50% for patients \<16 years of age * Adequate pulmonary, cardiac and liver function * Voluntary written consent (minor assent if appropriate) prior to the performance of any study related procedures not part of standard medical care 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

Treatments Being Tested

DRUG

Total Body Irradiation (TBI) (Plan 1)

300 cGy with thymic shielding on day -6

DRUG

Cyclophosphamide (CY) (Plan 1)

10 mg/kg IV daily on days -5, -4, -3, and -2

DRUG

Fludarabine (FLU)

35 mg/m2 IV daily on days -5, -4, -3, and -2

DRUG

Methylprednisolone (MP)

1 mg/kg IV q12h on days -5, -4, -3, -2, and -1

DEVICE

Donor mobilized PBSC infusion

T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation on day 0

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 or single day ANC \>3000 Arm 1 and Arm 3)

DRUG

Cyclophosphamide (CY) (Plan 2)

5 mg/kg IV daily on days -5, -4, -3, and -2

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.

DRUG

Alemtuzumab

Alemtuzumab 0.2 mg/kg is given IV over 2 hours daily for 5 days (total dose 1 mg/kg)

DRUG

Melphalan

If available, MEL dosing will be model-based using Bayesian methodology. If Bayesian methodology is unavailable, MEL dosing will be weight-based: MEL 70 mg/m2 for patients ≥10 kg (2.35 mg/kg for patients \<10 kg\^) IV for one dose over 30 minutes.

DRUG

Rituximab

Rituximab will be given once on treatment plans 1-3 on day -1.

Locations (1)

Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States