Stem Cell Transplantation for Primary Immunodeficiency

(PRO-RIC Trial)

Overseen By Paul Szabolcs, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Paul Szabolcs

Must be taking: Alemtuzumab, Melphalan, Thiotepa, Fludarabine

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial collects information on treatments for individuals with non-cancerous conditions requiring a stem cell transplant. The goal is to evaluate how well reduced-intensity chemotherapy, which is less harsh than usual, works with alemtuzumab, a medication that helps the body accept new cells, to prevent transplant complications and aid immune system recovery. It includes patients needing transplants due to conditions such as immune disorders, bone marrow issues, metabolic problems, anemia, or inflammatory diseases. Those who have experienced frequent immune system issues, bone marrow failure, or severe metabolic disorders might be suitable candidates for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that alemtuzumab can cause serious side effects, including immune system problems, reactions during administration, and an increased risk of infections. In some cases, it may even lead to strokes or damage to the arteries supplying blood to the brain.

Studies have found peripheral blood stem cell transplants (PBSCT) to be generally safe, though serious issues can sometimes occur shortly after the procedure. Most people tolerate the process well.

Reduced-intensity chemotherapy aims to lessen the side effects of traditional chemotherapy. However, it can still cause significant problems for some patients, as the goal is to be less harsh while remaining effective.

Lastly, recent studies have shown that umbilical cord blood transplantation (UCBT) is safe and practical, with successful donor matches and no transplant-related deaths reported. This makes it a promising option for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they offer potentially less intense options for patients with non-malignant disorders needing stem cell transplants. Unlike traditional bone marrow transplants (BMT) that often require high doses of chemotherapy, these treatments explore reduced-intensity chemotherapy (RIC), which might minimize side effects and be safer for more vulnerable patients. Additionally, peripheral blood stem cell transplants (PBSCT) and umbilical cord blood transplants (UCBT) provide alternative sources for stem cells, potentially increasing the availability of matches for patients. This variety of approaches could lead to more personalized treatment plans, improving outcomes and quality of life for patients.

What evidence suggests that this trial's treatments could be effective for preventing graft failure and aiding in immune reconstitution?

Research has shown that alemtuzumab can reduce the risk of relapses and worsening disability in patients. One study found that 13% of patients taking alemtuzumab experienced confirmed disability progression, compared to 21% of those on another treatment. Alemtuzumab also provides lasting benefits for up to five years without continuous treatment. It has proven especially effective for patients whose previous treatments were ineffective. These findings suggest that alemtuzumab could support immune recovery after stem cell transplants in non-cancerous conditions. ^{6 7 8 9 10}

Who Is on the Research Team?

Paul Szabolcs, MD

Principal Investigator

UPMC Children's Hospital of Pittsburgh

Are You a Good Fit for This Trial?

Inclusion Criteria

Patient, parent, or legal guardian must have given written informed consent.

Patient must be 2 months to 60 years (inclusive) of age at time of consent for all diagnoses.

A. Primary Immunodeficiency Syndromes

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Participants undergo a reduced-intensity conditioning regimen with alemtuzumab, hydroxyurea, fludarabine, melphalan, and thiotepa

2-3 weeks

Transplantation

Participants receive hematopoietic stem cell transplantation (HSCT) from a healthy donor

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including engraftment, GVHD, and immune reconstitution

up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Alemtuzumab
• BMT
• PBSCT
• Reduced-Intensity Chemotherapy
• UCBT

Who Is Running the Clinical Trial?

Paul Szabolcs

Lead Sponsor

Trials

8

Recruited

230+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10920415/

Real-World Retrospective Analysis of Alemtuzumab Outcomes ... The efficacy of alemtuzumab in reducing the risk of relapses, disability worsening, and brain volume loss has been demonstrated in clinical ...

2. lemtrada.com lemtrada.com/about/clinical-study-relapses

LEMTRADA® (alemtuzumab) Clinical Study Results 13% of patients who took LEMTRADA experienced confirmed disability progression compared with 21% of those who took Rebif.

3. neurology.org neurology.org/doi/10.1212/WNL.0000000000004354

Alemtuzumab CARE-MS II 5-year follow-up Alemtuzumab provides durable efficacy through 5 years in patients with an inadequate response to prior therapy in the absence of continuous treatment.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2211034820307914

Alemtuzumab outcomes by age: Post hoc analysis from the ... This analysis demonstrated alemtuzumab efficacy on relapse, disability, and MRI disease activity was improved vs. SC IFNB-1a over 2 years, and was maintained ...

5. journals.sagepub.com journals.sagepub.com/doi/10.1177/17562864231194823

Safety and efficacy with alemtuzumab over 13 years in ... Alemtuzumab demonstrated superior efficacy versus subcutaneous interferon (IFN) beta-1a in participants with relapsing-remitting multiple sclerosis in the 2- ...

6. lemtrada.com lemtrada.com/about/safety-side-effects

Safety & Side Effects: LEMTRADA® (alemtuzumab) LEMTRADA can cause serious side effects including autoimmune problems, infusion reactions, stroke, tears in your arteries that supply blood to your brain.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2001/alemmil050701LB.htm

Campath (ALEMTUZUMAB) Package Insert Safety data, except where indicated, are based on 149 patients with B-CLL enrolled in studies of Campath as a single agent administered at a ...

8. abmole.com abmole.com/literature/alemtuzumab-msds.html?srsltid=AfmBOoqmmTgsqegSDO-VGf3fmEQ5_hz3ZG3fOXN5o8x6Rd-BkCNfFeLm

Material Safety Data Sheet of Alemtuzumab This product does not contain any chemicals known to State of California to cause cancer, birth defects, or any other reproductive harm. 16. OTHER INFORMATION ...

9. mblbio.com mblbio.com/bio/dtl/dtlfiles/D204-3-v10-US.pdf

SAFETY DATA SHEET Carbon dioxide (CO2). Ensure adequate ventilation. Avoid inhalation of mist and contact with skin and eyes. For personal protection, see Section 8 of the SDS.

10. ema.europa.eu ema.europa.eu/en/documents/product-information/mabcampath-epar-product-information_en.pdf

MabCampath, INN-alemtuzumab - European Medicines Agency The most frequent serious adverse reactions are cytopenias, infusion reactions, and immunosuppression/infections. Undesirable effects in first line patients.