A Phase I Clinical Trial Testing the Safety of IL-21-Expanded, Off-the-shelf, Third-party Natural Killer Cells (KDS-1001) for the Induction of Relapsed/Refractory Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 19
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose (MTD) of membrane-bound interleukin-21-expanded haploidentical natural killer (NK) cells
研究概览
简要总结
This phase I trial studies the side effects of donor natural killer (NK) cell therapy in treating patients with acute myeloid leukemia that has come back (recurrent) or has not responded to treatment (refractory). Natural killer cells are a type of immune cell. Immunotherapy with genetically modified NK cells from donors may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread.
详细描述
PRIMARY OBJECTIVE:
I. To determine the safety of adoptive NK cell therapy using membrane-bound interleukin-21 (mbIL21)-expanded, off-the-shelf, third-party donor-derived NK cells in patients with relapsed/refractory acute myeloid leukemia (AML).
SECONDARY OBJECTIVES:
I. Estimate the complete response (CR, CR with incomplete hematologic recovery [CRi] & morphologic leukemia-free state [MLFS]).
II. Estimate the median relapse free survival. III. Estimate the median time to neutrophil and platelet count recovery. IV. Estimate the median duration of remission. V. Estimate the incidence of infectious complications. VI. Estimate percentage of patients receiving this regimen who are rendered transplant-eligible.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient Inclusion Criteria for Induction Phase
- •Primary Relapsed AML including
- •Relapsed AML after allogeneic stem cells
- •Isolated CNS or extramedullary disease (Note: a response monitoring plan must be developed a priori for subjects with extramedullary disease)
- •1-3 prior lines of therapy which includes chemotherapy, hypomethylating agents, venetoclax or targeted therapy.
- •Patient weight ≥ 42 kg
- •Performance status: Karnofsky or Lansky Performance Scale (PS) greater or equal to 70, or, ECOG score 0-
- •Renal function: Serum creatinine ≤ 2 mg/dl and/or creatinine clearance greater or equal than 40 cc/min.
- •Pulmonary function: FEV1, FVC and DLCO ≥ 50% of expected, corrected for hemoglobin.
- •Liver function: Total bilirubin ≤ 2 mg/dl or ≤ 2.5 x ULN for age (unless Gilbert's syndrome) and SGPT (ALT) ≤ 2.5 x ULN for age.
- •Cardiac function: left ventricular ejection fraction ≥ 40%.
- •CNS: Patients with seizure disorder are eligible if seizures well controlled.
- •Negative serum test to rule out pregnancy within 2 weeks prior to enrollment in females of childbearing potential (non-childbearing potential defined as premenarchal, greater than one year post-menopausal, or surgically sterilized).
- •Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator.
- •Ability to understand and willingness to sign the written informed consent document.
- •Negative serology for human immunodeficiency virus (HIV).
- •Patients on hydrocortisone for adrenal insufficiency or on inhaled or topical steroids are eligible.
- •Maintenance Phase: Patients that complete induction therapy and who achieve a CR/CRi/PR within the designated follow-up period and who are ineligible, unable or unwilling to undergo HSCT; these patients will not receive fludarabine or cytarabine.
排除标准
- •for Induction Phase:
- •Investigational therapies in the 3 weeks prior to beginning treatment on this protocol.
- •Patients receiving any concurrent therapy including but not limited to chemotherapy, targeted therapy, radiation therapy, or immunotherapy for R/R AML.
- •Any comorbidities that in the opinion of the investigator will preclude receiving fludarabine or cytarabine.
- •Uncontrolled infection, defined as an infection which has not resolved spontaneously or does not show evidence of significant resolution after initiating appropriate therapy. Asymptomatic viremia such as CMV, HPV, BK virus, HCV, HBV etc. is NOT considered as an exclusion criteria.
- •Uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
- •Active GVHD
- •Prednisone dose is > 20 mg/day or >0.25mg/kg, whichever is higher will be excluded.
- •Patients with donor-specific antibodies with MFI > 5000 will be ineligible
- •Maintenance Phase: Patients must continue to meet exclusion criteria as defined in Section 4.4.
研究组 & 干预措施
Conditioning Regimen
Fludarabine 30 mg/m2/day (day -6 to day -2) and Cytarabine 2g/ m2/day (days -6 to day -2)
干预措施: Cytarabine Hydrochloride (Drug)
Conditioning Regimen
Fludarabine 30 mg/m2/day (day -6 to day -2) and Cytarabine 2g/ m2/day (days -6 to day -2)
干预措施: Fludarabine (Drug)
Induction
Six doses of third-party-donor mbIL-21 expanded (KDS-1001) cells given thrice weekly for two weeks. Days may vary and KDS-1001 can be given from days 0 to 21
干预措施: Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells (Biological)
结局指标
主要结局
Maximum tolerated dose (MTD) of membrane-bound interleukin-21-expanded haploidentical natural killer (NK) cells
时间窗: Up to 63 days
The MTD will be defined as the highest safely tolerated dose where at most one patient in six experiences dose-limiting toxicity (DLT) during DLT observation period. DLT is defined as any steroid refractory acute graft versus host disease.
Incidence of adverse events
时间窗: Up to day 28
Toxicities will be assessed by type and grade using Common Terminology Criteria for Adverse Events version 5.0 and displayed in summary form by cohort and overall. Toxicities will be summarized and reported regardless of attribution and also only those attributed to NK cells.
次要结局
- Complete response (CR)(Up to day 56)
- CR with incomplete hematologic recovery(Up to day 56)
- Morphologic leukemia-free state(Up to day 56)
- Median duration of remission(Up to day 56)
- Incidence of infectious complications(Up to day 56)
- Median time to neutrophil and platelet count recovery(Up to day 56)
- Percentage of patients receiving the regimen who are rendered transplant-eligible(Up to day 56)
- Median relapse free survival(Up to day 56)
研究者
Sumithira Vasu
Principal Investigator
Ohio State University Comprehensive Cancer Center