Acute Myeloid Leukemia
Conditions
Keywords
Acute Myeloid Leukemia, High Risk Relapse, Complete Remission, Allogeneic Natural Killer Cells
Brief summary
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.
Interventions
BIOLOGICALCNDO-109-AANK Cells
Single dose, infusion
Sponsors
Coronado Biosciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The patient has pathologically documented AML and is in CR1 at the time of the screening visit 2. 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 3. A bone marrow aspiration performed within 21 days prior to the start of pre-infusion preparative therapy confirms the patient is in CR1 4. 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) 5. The patient is male or female, age 18 years or older 6. The patient has an ECOG performance status of 0, 1, or 2 7. 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 8. 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 \[LVEF\<40%\]) 9. 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) 10. 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 11. 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 12. 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 13. The patient has LVEF ≥40% by ECHO or MUGA scan and no clinically significant abnormalities in 12-lead ECG 14. The patient has a PT (or INR) and PTT up to 1.25×ULN 15. The patient must not be dependent on supplemental oxygen 16. The patient is using an effective contraceptive (per the institutional standard), if procreative potential exists 17. 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 18. 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
1. The patient had a previous bone marrow or stem cell transplant 2. The patient is seropositive for HIV 1, HIV 2, HBV, or HCV 3. The patient has a psychiatric, addictive, neurological or other disorder that compromises the ability to give informed consent or comply with study requirements 4. The patient is pregnant (confirmed by urine or serum pregnancy test) or lactating 5. The patient has a recently diagnosed active malignancy requiring therapy 6. The patient has an uncontrolled infection, or is receiving anti-fungal treatment for an ongoing infection 7. The patient has known hypersensitivity to bovine proteins 8. The patient has any condition that will place the patient at undue risk or discomfort as a result of adherence to study procedures 9. The patient requires treatment with corticosteroids at a dose \> 0.1 mg/kg/day or has a known allergy to DSMO
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Define MTD | up to 30 days post dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Additional Safety Profile Beyond MTD | up to 360 days post dose | 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. |
| Efficacy | from the date of documented CR until the first documented progression date or until day 360 post dose whichever is sooner | Determine relapse free survival (RFS) and overall survival (OS) following infusion with CNDO-109-Activated Allogeneic Natural Killer Cells. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CNDO-109-AANK Cells Dose 1 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.
CNDO-109-AANK Cells: Single dose, infusion | 3 |
| CNDO-109-AANK Cells Dose 2 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.
CNDO-109-AANK Cells: Single dose, infusion | 3 |
| CNDO-109-AANK Cells Dose 3 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.
CNDO-109-AANK Cells: Single dose, infusion | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | CNDO-109-AANK Cells Dose 1 | Total | CNDO-109-AANK Cells Dose 3 | CNDO-109-AANK Cells Dose 2 |
|---|---|---|---|---|
| Age, Continuous | 73 years STANDARD_DEVIATION 1 | 71.0 years STANDARD_DEVIATION 5.98 | 67.3 years STANDARD_DEVIATION 6.35 | 76.3 years STANDARD_DEVIATION 2.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 12 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 12 Participants | 6 Participants | 3 Participants |
| Region of Enrollment United States | 3 participants | 12 participants | 6 participants | 3 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 8 Participants | 6 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 1 / 6 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 1 / 3 | 1 / 3 | 3 / 6 |
Outcome results
Primary
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.
Time frame: up to 30 days post dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CNDO-109-AANK Cells Dose 1 | Define MTD | 3 Participants |
| CNDO-109-AANK Cells Dose 2 | Define MTD | 3 Participants |
| CNDO-109-AANK Cells Dose 3 | Define MTD | 6 Participants |
Secondary
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.
Time frame: up to 360 days post dose
Secondary
Efficacy
Determine relapse free survival (RFS) and overall survival (OS) following infusion with CNDO-109-Activated Allogeneic Natural Killer Cells.
Time frame: from the date of documented CR until the first documented progression date or until day 360 post dose whichever is sooner