Phase I Trial of Autologous Hybrid TREG/Th2 Cell (RAPA-501) Therapy for Amyotrophic Lateral Sclerosis

Minimum Age:

18 Years

Maximum Age:

N/A

Can participants use Riluzole?

Yes

Inclusion Criteria:

1. Male or female patients ≥ 18 years of age.

2. Patients with sporadic or familial amyotrophic lateral sclerosis (ALS) diagnosed as laboratory-supported possible, probable, or definite according to World Federation of Neurology El Escorial Criteria.

3. Must have a source of autologous T cells potentially sufficient to manufacture RAPA-501 cells, as defined by a peripheral CD3+ T cell count ≥ 800 cells per μl.

4. Patients may continue riluzole (Rilutek®) and/or edaravone (Radicava®) therapy if on a stable dose for ≥ one month prior to study entry.

5. Patients must be ≥ two weeks from major surgery, from edaravone therapy, and from participation in investigational trials.

6. Patients must have recovered from clinical toxicities (resolution of CTCAE [version 5] toxicity to a value of ≤ 2).

7. Serum creatinine ≤ less than or equal to 2.0 mg/dL.

8. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal.

9. Bilirubin ≤ 1.5 (except if due to Gilbert's disease).

10. Pulmonary slow vital capacity (SVC) ≥ 50% of predicted normal.

11. No history of abnormal bleeding tendency.

12. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future care.

For accrual to Cohort 3, additional eligibility inclusion criteria are as follows:

13. Ejection fraction by MUGA or 2-D echocardiogram within institution normal limits (applies only to study participants on cohort).

Exclusion Criteria:

1. Active uncontrolled infection.

2. Hypertension not adequately controlled by ≤ 3 medications.

3. History of documented pulmonary embolus within 6 months of enrollment.

4. Clinically significant cardiac pathology, as defined by: myocardial infarction within 6 months prior to enrollment, Class III or IV heart failure according to NYHA, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

5. Patients with history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis.

6. HIV, hepatitis B, or hepatitis C seropositive.

7. Pregnancy or breastfeeding patients.

8. Patients of childbearing age, or males who have a partner of childbearing potential, who are unwilling to practice contraception.

9. Patients may be excluded at the discretion of the PI or if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk.

For accrual to Cohort 3, additional eligibility exclusion criteria are as follows:

10. Calculated creatinine clearance value of < 70 mL/min, as calculated by the Cockcroft-Gault formula.

11. Diagnosis of malignancy (active).

12. Urinary obstruction.

13. Hypersensitivity to the agents in the PC regimen (pentostatin, cyclophosphamide).