A Safety and Efficacy Study of CD-19 t-haNK in Patients With B-cell Acute Lymphoblastic Leukemia

A Phase 1 Open-label Study of CD19 t-hANK as a Single Agent in Participants With Selected CD19+ Relapsed B-cell Acute Lymphoblastic Leukemia

This is a phase 1, open-label study to evaluate the safety and efficacy of CD19 t-haNK in patients with B-cell acute lymphoblastic leukemia. Up to 10 patients will receive at least 1 dose of study drug.

Up to 20 participants may be screened to enroll up to 10 patients who will receive at least 1 dose of study drug. The initial three participants will receive study drug in a staggered fashion, with a 7-day interval between each participant to evaluate the safety profile of the investigational product.

Patients will receive two 4-week cycles of IV CD19 t-haNK IV as a single agent regimen. Following a 1-week safety pause, patients will then receive 1 additional cycle of CD19 t-haNK given twice a week on an outpatient basis. Patients with no evidence of disease progression may be eligible to receive 2 additional cycles of treatment. Bone marrow aspirate will be performed for bone marrow analysis on day 22( +/- 3 days), and every 8 weeks( +/-1 week) thereafter. If there is no evidence of abnormal blasts present in bone marrow, measurable residual( MRD) testing will be performed. Treatment will be discontinued if a participant has confirmed progressive disease or unacceptable toxicity. Safety will be assessed for all participants.

Inclusion Criteria:

1. Age ≥ 12 years old.
2. Able to understand and provide a signed informed consent that fulfills the relevant Human Research Ethics Committee (HREC) or Independent Ethics Committee (IEC) guidelines.
3. Histologically or flow cytometry documented pre B-ALL.
4. Relapsed after achieving a 2nd complete remission (CR) or failed one cycle of re-induction therapy or with MRD positivity after ≥ 2 cycles of induction.
5. Must be willing to undergo a lumbar puncture (LP) for CSF analysis and administration of IT chemotherapy.
6. Performance status: Lansky score >60%, for participant ≥12 to <16 years. Eastern Cooperative Oncology Group (ECOG) score of ≤ 1 for participants ≥ 16 years.
7. Expected survival > 16 weeks.
8. Stated willingness to comply with study procedures.
9. Able to attend required study visits and return for adequate follow-up, as required by this protocol.
10. Agreement to practice effective contraception for female participants of childbearing potential and nonsterile males. Female participants of childbearing potential must agree to use effective contraception while on study and for at least 30 days after the last dose of study drug. Nonsterile male participants must agree to use a condom while on study and for up to 5 months after the last dose of study drug. Effective contraception includes orals, injectables, surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm), and implants such as intrauterine devices (IUDs).

All inclusion criteria must be answered "yes" for a participant to participate in the trial.

Exclusion Criteria:

1. Participants with T-cell leukaemia and Burkitt's M3 leukaemia.

2. Known hypersensitivity or allergy to any component of the study medication(s), including sulfa-containing (eg, dimethyl sulfoxide, DMSO).

3. Inadequate organ function, evidenced by the following laboratory results:

   1. Serum creatinine ≥ 2 mg/dL
   2. Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) ≥ 5 upper limit of normal (ULN)
   3. Total bilirubin ≥ 2 mg/dL

4. Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the participant at high risk for treatment related complications.

5. History of significant autoimmune disease OR active, uncontrolled autoimmune phenomenon: such as systemic lupus erythematous, Wegner's glomerulonephritis, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura requiring steroid therapy defined as > 20 mg of prednisone or equivalent daily.

6. History of allogeneic hematopoietic stem-cell transplantation (HSCT) requiring ongoing systemic graft versus host disease (GvHD) therapy.

7. History of receiving allograft organ transplant requiring immunosuppression.

8. Participants post solid organ transplant who develop high grade lymphomas or leukaemias.

9. Nonmalignant CNS disease (eg, stroke, epilepsy, vasculitis, or neurodegenerative disease).

10. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

11. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association Class 2 or higher; or serious cardiac arrhythmia requiring medication.

12. Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids defined as > 20 mg of prednisone or equivalent daily, excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in participants who have known contrast allergies is allowed.

13. Currently taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.

14. History of human immunodeficiency virus (HIV) with current CD4+ T-cell count < 350 cells/μL and a detectable HIV viral load.

15. Known carriers of hepatitis B virus (HBV) infection that is currently hepatitis B surface antigen (HBsAg) positive.

16. Concurrent active malignancy other than basal or squamous cell carcinomas of the skin.

17. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.

18. Women who are pregnant or breastfeeding.

All exclusion criteria must be answered "no" for a participant to participate in the trial.