Allogeneic Hematopoietic Cell Transplantation for Disorders of T-cell Proliferation and/or Dysregulation

Summary

Background:

Blood stem cells in the bone marrow make all the cells to normally defend a body against disease. Allogeneic blood or marrow transplant is when these stem cells are transferred from one person to another. Researchers think this treatment can provide a new, healthy immune system to correct T-cell problems in some people.

Objective:

To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with T-cell problems.

Eligibility:

Donors: Healthy people ages 4 and older

Recipients: People the same age with abnormal T-cell function causing health problems

Design:

All participants will be screened with:

* Medical history
* Physical exam
* Blood, heart, and urine tests

Donors will also have an electrocardiogram and chest x-ray. They may have veins tested or a pre-anesthesia test.

Recipients will also have lung tests.

Some participants will have scans and/or bone marrow collected by needle in the hip bones.

Donors will learn about medicines and activities to avoid and repeat some screening tests.

Some donors will stay in the hospital overnight and have bone marrow collected with anesthesia.

Other donors will get shots for several days to stimulate cells. They will have blood removed by plastic tube (IV) in an arm vein. A machine will remove stem cells and return the rest of the blood to the other arm.

Recipients will have:

* More bone marrow and a small fragment of bone removed
* Dental, diet, and social worker consultations
* Scans
* Chemotherapy and antibody therapy for 2 weeks
* Catheter inserted in a chest or neck vein to receive donor stem cells
* A hospital stay for several weeks with more medicines and procedures
* Multiple follow-up visits

Conditions

• Lymphoproliferative Disorders
• Autoimmune Lymphoproliferative
• Primary T-cell Immunodeficiency Disorders
• Immune System Diseases
• Common Variable Immunodeficiency

Interventions

DRUG

e-ATG

During Immunosuppression Only Conditioning (IOC) and Reduced Intensity Conditioning (RIC).

PROCEDURE

Immunosuppression Only Conditioning

Equine anti-thymocyte globulin (e-ATG) 40 mg/kg intravenous (IV) once daily for days -14 and -13. Prednisone: Tapering doses, given orally daily, and given prior to each daily dose of e-ATG on days -14 and -13, Pentostatin:4 mg/m\^2/day IV on days -9 and -5, cyclophosphamide:5 mg/kg orally daily on days -9 through -2.

PROCEDURE

Reduced Intensity Conditioning

Equine anti-thymocyte globulin (e-ATG) 40 mg/kg intravenous (IV) once daily for days -14 and -13. Prednisone: Tapering doses, given orally daily, and given prior to each daily dose of e-ATG on days -14 and -13, Pentostatin:4 mg/m\^2/day IV on days -11 and -7, cyclophosphamide: 5 mg/kg orally daily on days -11 through -4, Busulfan IV, pharmacokinetically dosed, on days -3 and -2.

DRUG

GVHD Prophylaxis

High-dose, post-transplantation cyclophosphamide (PTCy) 25-50 mg/kg on days +3 and +4, Mesna: 25-50 mg/kg weight-based dosing, Tacrolimus 0.02 mg/kg on days +5 through +90, and mycophenolate mofetil (MMF) 15 mg/kg on days +5 through +25.

PROCEDURE

Allogeneic HSC

Stem cell transplant

DRUG

Bisulfan

During Reduced Intensity Conditioning (RIC).

DRUG

Prednisone

During Immunosuppression Only Conditioning (IOC) and Reduced Intensity Conditioning (RIC).

DRUG

Cyclophosphamide

During Immunosuppression Only Conditioning (IOC), Reduced Intensity Conditioning (RIC) and Graft-versus-host disease prophylaxis (GVHD).

DRUG

MMF

During Graft-versus-host disease prophylaxis (GVHD).

DRUG

Mesna

During Graft-versus-host disease prophylaxis (GVHD).

DRUG

Tacrolimus

During Graft-versus-host disease prophylaxis (GVHD).

DRUG

Pentostatin

During Immunosuppression Only Conditioning (IOC) and Reduced Intensity Conditioning (RIC).

DIAGNOSTIC_TEST

PFTs

Screening ≤4 weeks pretreatment (rx), Day +180 (≤ 14 days), Day +36 (± 21 days), Day +548 (18 months) (± 28 days), and at 2 years and yearly thereafter through +5 years (± 56 days).

DIAGNOSTIC_TEST

DEXA

Baseline, Day +365 (± 21 days), at 2 years and yearly thereafter through +5 years (± 56 days), and as clinically indicated after hematopoietic cell transplant (HCT).

PROCEDURE

Bone Marrow Aspirate & Biopsy

Baseline, Day +60 (± 3 days) and Day +365 (±21 days).

DIAGNOSTIC_TEST

EKG

Baseline

DIAGNOSTIC_TEST

2D ECHO

Screening ≤4 weeks pretreatment (rx), Day +180 (≤ 14 days), Day +36 (± 21 days), Day +548 (18 months) (± 28 days), and at 2 years and yearly thereafter through +5 years (± 56 days).

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Dimana Dimitrova, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

4 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-09-04

Primary Completion

2025-04-03

Completion

2030-04-03

FDA Drug

Yes

Countries

• United States

Study Locations