NK Cell Therapy for AML

A Phase 1 Study of Evaluating Preliminary Safety and Efficacy of CT101a in the Treatment of Relapsed or Refractory (r/r) AML Patients

This is a single-arm, open-label, non-randomized, multiple-dose, phase 1 dose escalation study evaluating the safety, efficacy and PK of CT101a in patients with relapsed/refractory acute myeloid leukemia.

Primary Objective:

To evaluate the safety and tolerability of CT101a and estimate the MTD in Chinese patients.

Secondary Objective:

To determine the preliminary efficacy of CT101a in the treatment of r/r AML by IWG response rate; To determine the duration of response, time to progression, disease-free survival, and overall survival of AML patients treated with CT101a.

Exploratory Objective:

To investigate and analyze the correlation between the donor KIR gene and the efficacy in the subject.

To explore the feasibility and safety of multiple doses of CT101a in the treatment of r/r AML.

To detect blood samples and bone marrow samples before and after CT101a infusion by single cell sequencing method, and to perform difference analysis.

This is a single-arm, open-label, non-randomized, multiple-dose, phase 1 dose escalation study evaluating the safety, efficacy and PK of CT101a in patients with relapsed/refractory AML.

This clinical study is to evaluate the safety, MTD and preliminary efficacy of CT101a in patients with relapsed/refractory AML. Up to 9-18 patients will be enrolled.

Inclusion Criteria:

1. Patients diagnosed with relapsed or refractory AML:

   1. For patients with relapsed AML: after complete response (CR), leukemia cells or blast cells in the bone marrow reappear >5% (except for other reasons such as bone marrow regeneration after consolidation chemotherapy).
   2. For patients with refractory AML: initial cases who have been treated with standard regimens for 2 courses of treatment that are not effective; after CR, they undergo consolidation and intensive treatment and relapse within 12 months; those who relapse after 12 months but are ineffective after conventional chemotherapy; those who relapse for 2 or multiple times.
   3. AML patients with disease progression after transplantation.

2. Male or female ≥ 18 years old.

3. ECOG Performance Status 0 to 2.

4. Life expectancy ≥3 months.

5. Available HLA-haploidentical donor meeting the following criteria:

   1. Related donor (parent, sibling, offspring, or offspring of sibling);
   2. At least 18 years of age;
   3. HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A&B locus;
   4. In general, the donor is healthy and can tolerate leukapheresis for collecting NK cells required in this study;
   5. Negative for HCV antibody, five items of HBV, HIV antibody and syphilis on donor viral screening;
   6. The female donor of childbearing potential must have a negative pregnancy test within screening.
   7. Voluntary written consent to participate in this study.

6. Adequate organ function as defined below:

   1. Total bilirubin<2 mg/dL;
   2. AST(SGOT)/ALT(SGPT) <3.0 x ULN;
   3. Creatinine within normal institutional limits;
   4. Oxygen saturation ≥90% on room air;
   5. Ejection fraction ≥35%.

7. Able to be off corticosteroids and any other immune suppressive medications beginning on 3 days before the CT101a infusion and continuing until 28 days after the CT101a infusion. However, use of low-level corticosteroids is permitted at the judgment of the investigator if deemed medically necessary. Low-level corticosteroid use is defined as 10mg or less of prednisone (or equivalent for other steroids) per day.

8. Women of childbearing potential must have a negative pregnancy test within screening. Female and male patients (along with their female partners) must agree to use two forms of acceptable contraception, including one barrier method, during participation in the study.

9. Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

1. Acute or chronic GVHD with ongoing active systemic treatment.
2. Circulating blast count >30,000/μL by morphology or flow cytometry.
3. Prior treatment with ML NK cell therapy within 3 months prior to screening.
4. Patients who are undergoing any approved or investigational chemotherapy and anti-leukemic therapy with small molecule-targeted drugs within the 14 days prior to the first dose of fludarabine.
5. Presence of any severe or uncontrolled systemic disease or condition.
6. Patients with active infection requiring systemic therapy within 2 weeks prior to screening.
7. HBsAg positive and HBV DNA is detectable or above the cut-off value or positive HCV antibody or positive HIV antibody or positive syphilis test.
8. New progressive pulmonary infiltrates on screening chest X-ray or chest CT scan that have not been evaluated with bronchoscopy.
9. Patients with a significant cardiovascular disease or condition.
10. Inadequate bone marrow reserve or organ function.
11. Other patients judged inappropriate for this study by the investigators.