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Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders

ConditionsFanconi AnemiaSevere Aplastic AnemiaMyelodysplastic SyndromesT Cell Receptor Alpha/Beta DepletionTelomere Biology DisorderBone Marrow FailureDyskeratosis CongenitaTelomere Biology Disorders
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
AgeUp to 65
SponsorMasonic Cancer Center, University of Minnesota

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Diagnosis of Fanconi anemia

Age <65 years of age

Severe aplastic anemia (SAA)

Myelodysplastic features

Disqualifiers

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

an HLA-A, B, DRB1 matched sibling donor (matched sibling)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Total Body Irradiation (TBI) (Plan 1)

    Drug

    300 cGy with thymic shielding on day -6

  • Cyclophosphamide (CY) (Plan 1)

    Drug

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

  • Fludarabine (FLU)

    Drug

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

  • Methylprednisolone (MP)

    Drug

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

  • Donor mobilized PBSC infusion

    Device

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

  • G-CSF

    Drug

    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)

  • Cyclophosphamide (CY) (Plan 2)

    Drug

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

  • Rituximab

    Drug

    200 mg/m2 IV once on day -1

  • Busulfan

    Drug

    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.

  • Alemtuzumab

    Drug

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

  • Melphalan

    Drug

    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.

  • Rituximab

    Drug

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

Treatment groups

48 Participants
are divided into 5 treatment groups
Group A: Treatment Plan 1: TBI 300 , CY, FLU, MP, Rituximab in patients with Fanconi AnemiaExperimental treatment 7 interventions
Group B: Treatment Plan 2: CY, FLU, MP, Rituximab in patients with Fanconi AnemiaExperimental treatment 6 interventions
Group C: Treatment Plan 3: BU, Cy, FLU, MP and Rituximab in patients with Fanconi AnemiaExperimental treatment 5 interventions
Group D: Treatment Plan 4: CY, FLU, and alemtuzumabExperimental treatment 3 interventions
Group E: Treatment Plan 5: CY, FLU, melphalan (MEL), and alemtuzumab.Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

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

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

Time frame
Day 100

Secondary outcomes

1

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)

Time frame
Day 42
2

Platelet engraftment

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
3

Acute graft versus host disease (aGVHD)

Incidence of grade III-IV acute graft versus host disease

Time frame
Day 100
4

Chronic graft versus host disease (cGVHD)

Incidence of chronic graft versus host disease after transplant

Time frame
1 Year after transplant

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Masonic Cancer Center, University of Minnesota

Lead sponsor

Source ClinicalTrials.gov
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