CD19 t-haNK treatment for 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 trial will try CD19 t-haNK, an intravenous immune therapy, in people aged 12 and older with relapsed or minimal-residual B-cell acute lymphoblastic leukemia.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: ImmunityBio, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 2 sites (Johannesburg and 1 other locations)
• Trial ID: NCT07556757 on ClinicalTrials.gov

What this trial studies

This open-label Phase 1 trial will enroll up to 10 patients with relapsed or MRD-positive B-ALL to receive CD19 t-haNK as a single-agent intravenous therapy. The first three participants will be dosed in a staggered fashion 7 days apart for initial safety monitoring; up to 20 may be screened to achieve the enrollment target. Treatment includes two 4-week cycles, a one-week safety pause, then an additional outpatient cycle given twice weekly, with up to two extra cycles allowed for those without progression. Bone marrow aspirates will be performed on day 22 (±3 days) and every 8 weeks (±1 week) with MRD testing if no abnormal blasts are seen, and safety will be monitored continuously with discontinuation for confirmed progression or unacceptable toxicity.

Who should consider this trial

Good fit: Ideal candidates are people aged 12 or older with histologically or flow-confirmed pre-B B-ALL who are relapsed after a second remission, have failed one cycle of re-induction, or have MRD positivity after at least two induction cycles, and who meet performance status and procedural requirements.

Not a fit: Patients with rapidly progressive disease, poor organ function or performance status, or whose leukemia lacks CD19 expression may not receive benefit from this treatment.

Why it matters

Potential benefit: If successful, this approach could offer a new CD19-targeted immune therapy that reduces leukemia burden and helps extend remission in relapsed B-ALL.

How similar studies have performed: Other CD19-targeted immunotherapies such as CAR-T cells have shown strong efficacy in relapsed B-ALL, but CD19-directed engineered NK therapies like t-haNK are relatively novel with limited clinical data to date.

Eligibility criteria

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.

Where this trial is running

Johannesburg and 1 other locations

• Dr Jackie Thomson Inc — Johannesburg, South Africa (Recruiting)
• Alberts Cellular Therapy — Pretoria, South Africa (Recruiting)

Study contacts

• Study coordinator: Kayleigh Russell

Conditions B-ALL; Leukemia; B-Cell; Acute; Lymphoblastic