Stem cell transplant for patients with immune system disorders

A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for Patients With Inborn Errors of Immunity

This study is testing if a stem cell transplant from a matched donor can help people aged 4 to 69 with immune system disorders feel better and improve their health.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 4 Years to 69 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: alemtuzumab, cyclophosphamide, fludarabine
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT04339777 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of allogeneic hematopoietic stem cell transplantation in patients with inborn errors of immunity (IEI). Participants aged 4 to 69, who have significant health issues due to primary immunodeficiency or related disorders, will receive stem cells from matched donors. The study aims to achieve sustained donor engraftment and restore normal immune function. Comprehensive screening and conditioning regimens will be employed to ensure the best outcomes for participants.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 4-69 with a known or suspected inborn error of immunity who have not responded to standard treatments.

Not a fit: Patients with stable immune function or those who do not have a suitable donor may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could potentially cure patients with severe immune deficiencies, significantly improving their quality of life.

How similar studies have performed: Previous studies have shown promising results with allogeneic stem cell transplantation in similar patient populations, indicating a potential for success in this approach.

Eligibility criteria

* INCLUSION CRITERIAl:
* Age \>= 4 years and \<=69 yo with Weight \>=12 kilograms
* Mutation in a known monogenic (IEI) gene performed by a CLIA certified laboratory, who have failed standard medical management, or when no standard medical management is available.

OR

Patients without a known IEI mutation may be eligible if they have a clinical history that is characteristic of an individual with an immune defect including a history of infections requiring prolonged courses of therapy or evidence of immune dysregulation manifested by autoimmune/autoinflammatory disease, atopy, hemophagocytic lymphohistiocytosis, hypogammaglobulinemia, or impaired response to vaccination. A virally-driven malignancy alone will also constitute basis for inclusion.

* Availability of an 8/8, 7/8, or 6/8 HLA-matched related or unrelated donor (if the mismatch is at DQ this will be considered an 8/8 matched donor), or a haploidentical related donor. Karnofsky or Lansky performance status of \>= 40%
* Adequate end-organ function, as measured by:

  --Left ventricular ejection fraction \> 40%, preferably by 2-D echocardiogram (ECHO) obtained within 60 days prior to enrollment.
* Creatinine: Adult patients: \<= 2.0 mg/dl and creatinine clearance \>= 30 ml/min; Pediatric patients (\<18 years old): creatinine \< 1.5 mg/dL and a creatinine clearance, using the Schwartz Formula \> 30 mL/min/1.73m\^2.

  * Serum conjugated bilirubin \< 2.5 mg/dl; serum ALT and AST \<= 5 times upper

limit of normal.

--Pulmonary function tests: FEV1 \> 30% and DLCO \>30%. Children who are unable to have DLCO assessed due to age, are still eligible if no evidence of dyspnea at rest and no need for supplemental oxygen.

* Ability of subject or parent/guardian to understand and the willingness to sign a written informed consent document. For subjects \<18 years old, their legal guardian must give informed consent. Pediatric patients will provide assent.
* As therapeutic agents used in this trial may be harmful to a fetus, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one year post-allo HCT. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in the study, she should inform her treating physician immediately.
* Willingness to remain in the NIH hospital or, if discharged, stay close to the NIH, for a minimum of 100 days after transplant or longer, if there are complications. If outpatient in the first 100 days after transplant, patient must commit to having an adult caregiver with them at all times.

EXCLUSION CRITERIA:

* Patients who are receiving any other investigational agents (with the exception of virus-specific therapy e.g. cytotoxic T-cells for the treatment of viral infection/reactivation prior to allo HCT).
* Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
* HIV-positive patients are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents (steroids, cyclophosphamide, busulfan, tacrolimus, sirolimus, MMF, G-CSF, alemtuzumab) used in the study
* Active psychiatric disorder which is deemed by the PI to have significant risk of compromising compliance with the transplant protocol or which does not allow for appropriate informed consent
* Pregnant women are excluded from this study because the study agents have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study agents, breastfeeding should be discontinued if the mother is treated with the study agents.
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Sung-Yun Pai, M.D. — National Cancer Institute (NCI)
• Study coordinator: Shannon L Knight, R.N.

Conditions Lymphoproliferative Disorders; Autoimmune Lymphoproliferative; Immune System Diseases; Common Variable Immunodeficiency; Primary T-cell Immunodeficiency Disorders; Autoimmunity; Haploidentical; Opportunistic Infection