Allogeneic Hematopoietic Stem Cell Transplant for Patients With Inborn Errors of Immunity

Summary

Background:

During a transplant, blood stem cells from one person are given to someone else. The cells grow into the different cells that make up the immune system. This can cure people with certain immunodeficiencies. But transplant has many risks and complications.

Objective:

To see if stem cell transplant can be successfully performed in people with primary immunodeficiency disease and cure them.

Eligibility:

People ages 4-69 for whom a primary immunodeficiency (PID) or Primary Immune Regulatory Disorder (PIRD), has caused significant health problems and either standard management has not worked or there are no standard management options, along with their donors

Design:

Donors will be screened under protocol 01-C-0129. They will donate blood or bone marrow.

Participants will be screened with:

Medical history

Physical exam

Blood, urine, and heart tests

CT or PET scans

Before transplant, participants will have dental and eye exams. They will have a bone marrow biopsy. For this, a needle will be inserted through the skin into the pelvis to remove marrow.

Participants will be hospitalized before their transplant. They will have a central catheter put into a vein in their chest or neck. They will get medications through the catheter to prevent complications. Participants will get stem cells through the catheter. They will stay in the hospital for at least 4 weeks. They will give blood, urine, bone marrow, and stool samples. They may need blood transfusions. They may need more scans. They will take more medications.

Participants will have visits on days 30, 60, 100, 180, and 360, and 24 months after the transplant. Then they will have visits once a year for about 5 years

Conditions

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

Interventions

DRUG

Busulfan test dose

0.8 mg/kg IV infusion over 2 hours

DRUG

Fludarabine

40 mg/m2 IV infusion over 30 min once daily for 4 days

DRUG

Busulfan

AUC Targeted Dose based on busulfan test dose PKs, IV infusion over 3 hours once daily (3.2 mg/kg IV per day will be the default dose) per the below time frame: For 10/10 Matched Related and Unrelated Donor Recipients For the High Intensity Arm, the busulfan dose will be given for 4 days (-6, -5, -4, and -3). For Intermediate Intensity Arm, the busulfan dose will be given for 3 days (-6,-5, and -4). For Low Intensity Arm, the busulfan dose will be given for 2 days on days (-6 and -5). 9/10 HLA Matched Related or Unrelated Donor Recipients For the High Intensity Arm, the busulfan dose will be given for 3 days (-6, -5, and -4). For the the Intermediate Intensity Arm, the busulfan dose will be given for 2 days (-6 and -5). For the Low Intensity Arm, the busulfan dose will be given for 1 day on day (-6).

DRUG

Alemtuzumab

Alemtuzumab will be given if there is evidence of immune dysregulation 10 mg/m2 SC divided over three days (-14, -13, and -12)

RADIATION

Total body Irradiation

200 cGy Transplant Day -1 (Only for 9/10 HLA Matched Related or Unrelated Donor Recipients )

PROCEDURE

Allogeneic HSCT

Stem cell transplant

DRUG

Tacrolimus (Tacro)

Tacrolimus 0.02 mg/kg IV continuous infusion over 24 hours starting on day +5

DRUG

Mycophenolate mofetil (MMF)

Mycophenolate mofetil 15 mg/kg IV over 2 hours three times a day starting on day +5 will continue until Approximately+35 (+/- two days)

DRUG

Cyclophosphamide (Cytoxan)

Cyclophosphamide: 50 mg/kg IV once daily over 2 hours on days +3 and +4, dosed according to ideal body weight

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Sung-Yun Pai, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

4 Years

Max Age

69 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-09-22

Primary Completion

2026-10-01

Completion

2027-11-30

FDA Drug

Yes

Countries

• United States

Study Locations