CNDO-109-AANK for AML in First Complete Remission (CR1)

Study Overview
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Brief Summary
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This is a multi-center, open-label, non-controlled, non-randomized dose-escalating Phase 1 clinical study designed to examine the safety of infusing escalating doses of CNDO-109-Activated Allogeneic Natural Killer Cells-(from a first or second degree relative), after a preparatory chemotherapy regimen, in adult patients with acute myeloid leukemia (AML) who are in their first complete remission at the time of enrollment, are not candidates for stem cell transplant, and are considered to be at high risk for recurrence.

Official Title
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A Phase 1/2 Study of CNDO-109-Activated Allogeneic Natural Killer Cells in Patients With High Risk Acute Myeloid Leukemia in First Complete Remission (CR1)

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: CNDO-109-AANK Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has pathologically documented AML and is in CR1 at the time of the screening visit The patient achieved CR1 within 10 weeks of the screening visit; the patient may have received post-remission consolidation therapy (except for transplant) prior to the screening visit A bone marrow aspiration performed within 21 days prior to the start of pre-infusion preparative therapy confirms the patient is in CR1 The patient has either refused or is not considered an appropriate immediate candidate for transplantation and is considered to be at high risk for recurrence by having at least one of the following prognostic factors: High risk cytogenetics (-5, -7, del(5q), abnormal 3q, 11q23 translocations, complex cytogenetics) or if cytogenetics are normal the presence of a FLT3 mutation without a NPM1 mutation Age > 60 years Antecedent hematological disorder (AHD) AML that is considered to be therapy-related FAB subtype M0 (minimally differentiated acute myeloblastic leukemia), M6 (acute erythroid leukemias, including erythroleukemia (M6a) and pure erythroid leukemia (M6b)), or M7 (acute megakaryoblastic leukemia) The patient is male or female, age 18 years or older The patient has an ECOG performance status of 0, 1, or 2 The patient has an available NK cell donor who is a HLA haploidentical first-degree (parent, child, or sibling) or second-degree (child of a sibling) relative; minimum testing will be for HLA-A, HLA-B, and HLA-DR with donors matched for 3/6, 4/6 or 5/6 antigens The patient has an absence of coexisting medical problems that would significantly increase the risk of the chemotherapy procedure (e.g. poor left ventricular ejection fraction [LVEF<40%]) The patient has recovered from reversible toxicity from prior therapy. Permanent and stable side effects or changes are acceptable if ≤ Grade 1 (CTCAE, v4.03) The patient has serum creatinine <2×ULN and not rising for at least 2-4 weeks before chemotherapy. If elevated, the 24-hour creatinine clearance must be >50 mL/min The patient has serum total bilirubin < 2 g/dL (unless the patient has a diagnosis of Gilbert's disease), SGOT (ALT) <3.5×ULN, and SGPT (AST) <3.5×ULN The patient has an absolute neutrophil count (ANC) ≥1000/µL, platelets ≥100,000/µL and is not transfusion dependent for platelets and/or red cells The patient has LVEF ≥40% by ECHO or MUGA scan and no clinically significant abnormalities in 12-lead ECG The patient has a PT (or INR) and PTT up to 1.25×ULN The patient must not be dependent on supplemental oxygen The patient is using an effective contraceptive (per the institutional standard), if procreative potential exists The patient must be willing and able to comply with all study protocol requirements. The patient or a legally authorized representative must fully understand all elements of the informed consent and have signed the informed consent according to institutional and federal regulatory requirements The patient has not received an investigational chemotherapy within the last 28 days prior to the screening visit and has never received investigational immunotherapy. In addition, the patient must not receive treatment for AML (including treatment with IL-2 or IFNγ) in the interval of time between the screening visit and initiation of pre-infusion preparative therapy Exclusion Criteria: The patient had a previous bone marrow or stem cell transplant The patient is seropositive for HIV 1, HIV 2, HBV, or HCV The patient has a psychiatric, addictive, neurological or other disorder that compromises the ability to give informed consent or comply with study requirements The patient is pregnant (confirmed by urine or serum pregnancy test) or lactating The patient has a recently diagnosed active malignancy requiring therapy The patient has an uncontrolled infection, or is receiving anti-fungal treatment for an ongoing infection The patient has known hypersensitivity to bovine proteins The patient has any condition that will place the patient at undue risk or discomfort as a result of adherence to study procedures The patient requires treatment with corticosteroids at a dose > 0.1 mg/kg/day or has a known allergy to DSMO

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CNDO-109-AANK Cells Dose 1<br>In stage 1, patients will receive one of three doses of CNDO-109-AANK cells, and the lowest of these three doses (dose 1) is 3×10^5 cells/kg recipient body weight. In stage 2, the MTD will have been determined and all patients will receive either Dose 1, Dose 2 or Dose 3. | Biological: CNDO-109-AANK Cells<br>* Single dose, infusion<br>* Other names: CNDO-109-Activated Allogeneic Natural Killer Cells;|
| Experimental: CNDO-109-AANK Cells Dose 2<br>In stage 1, patients will receive one of three doses of CNDO-109-AANK cells, and the middle dose of these three doses (dose 2) is 1×10^6 cells/kg recipient body weight. In stage 2, the MTD will have been determined and all patients will receive either Dose 1, Dose 2 or Dose 3. | Biological: CNDO-109-AANK Cells<br>* Single dose, infusion<br>* Other names: CNDO-109-Activated Allogeneic Natural Killer Cells;|
| Experimental: CNDO-109-AANK Cells Dose 3<br>In stage 1, patients will receive one of three doses of CNDO-109-AANK cells, and the highest dose of these three doses (dose 3) is 3×10^6 cells/kg recipient body weight. In stage 2, the MTD will have been determined and all patients will receive either Dose 1, Dose 2 or Dose 3. | Biological: CNDO-109-AANK Cells<br>* Single dose, infusion<br>* Other names: CNDO-109-Activated Allogeneic Natural Killer Cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define MTD | The primary objective is to define the maximum tolerated dose (MTD), or the maximum tested dose where multiple dose-limiting toxicities (DLTs) are not observed, of CNDO-109-Activated Allogeneic Natural Killer Cells infused after preparative chemotherapy, administered to patients with acute myeloid leukemia (AML) who are in their first complete remission (CR1) at the time of enrollment and are considered to be at high risk for recurrence. The MTD outcome measure is presented as number of participants with DLTs. | up to 30 days post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Additional Safety Profile Beyond MTD | Characterize the safety profile of CNDO-109-Activated Allogeneic Natural Killer Cells infusion after preparative therapy by measurement of adverse events, safety labs, vital signs, bone marrow biopsy/aspiration and physical examination. | up to 360 days post dose | 
| Efficacy | Determine relapse free survival (RFS) and overall survival (OS) following infusion with CNDO-109-Activated Allogeneic Natural Killer Cells. | from the date of documented CR until the first documented progression date or until day 360 post dose whichever is sooner | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myeloid Leukemia, High Risk Relapse, Complete Remission, Allogeneic Natural Killer Cells