Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders

Summary

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.

Conditions

• Fanconi Anemia
• Severe Aplastic Anemia
• Myelodysplastic Syndromes
• T Cell Receptor Alpha/Beta Depletion
• Telomere Biology Disorder
• Bone Marrow Failure
• Dyskeratosis Congenita
• Telomere Biology Disorders

Interventions

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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota

  lead OTHER

Principal Investigators

• Margaret MacMillan, MD, Msc, FRCPC · Masonic Cancer Center, University of Minnesota

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-11-13

Primary Completion

2027-01-01

Completion

2029-01-05

FDA Device

Yes

Countries

• United States

Study Locations