CIML NK Cells With Venetoclax for AML
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorDana-Farber Cancer Institute
About this trial
The purpose of this research study is to test the safety and to explore the effectiveness of infusing cytokine- induced memory-like (CIML) natural killer (NK) cells in combination with Interleukin-2 (IL-2) and standard-of-care venetoclax as a treatment for Acute Myeloid Leukemia (AML) with measurable residual disease or oligoblastic (\< 20% blasts in the bone marrow) disease.
Names of the study therapies involved in this study are:
* Lymphodepleting therapy with Fludarabine and Cyclophosphamide prior to CIML NK cell infusion * CIML NK (a cellular therapy) * IL-2 (a recombinant, human glycoprotein) * Venetoclax (a selective inhibitor of BCL-2 protein)
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of AML or MDS/AML (10-19% blasts) by 2022 ELN criteria. Historical test results (either peripheral blood or bone marrow) can be used to establish this diagnosis.
Age ≥ 18 years old
At time of screening patient has received any prior lines of therapy including prior chemotherapy and any prior stem cell transplant, provided that the stem cell transplant is > 6 months ago with no ongoing need for immunosuppressive therapy for active graft-versus-host disease.
2022 ELN adverse risk karyotype: t(6;9)(p23.3;q34.1)/DEK::NUP214; t(v;11q23.3)/KMT2A-rearranged; t(9;22)(q34.1;q11.2)/BCR::ABL1; t(8;16)(p11.2;p13.3)/KAT6A::CREBBP; inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/ GATA2, MECOM(EVI1), t(3q26.2;v)/MECOM(EVI1)-rearranged; -5 or del(5q); -7; Complex karyotype, monosomal karyotype
Disqualifiers
Participants are excluded if they received prior allogeneic stem cell transplant ≤ 6 months ago or require immunosuppressive therapy for active GVHD, received prior donor lymphocyte infusion (DLI) ≤ 2 months ago, or received prior organ transplant or donor lymphocyte infusion (DLI), CAR-T cell or NK cell therapy at any time.
Persisting Grade > 2 non hematologic toxicity related to prior therapy is excluded; however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease requiring any steroids >> the equivalent dose of 10 mg of prednisone or other immunosuppressive therapies at the time of this registration visit (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]) and motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis). Patients with Hashimoto's thyroiditis are eligible to go on study.
Pregnant women are excluded from this study because of the unknown teratogenic risk of CIML NK cells and IL-2 and with the potential for teratogenic or abortifacient effects by Flu/Cy chemotherapy regimen. Breastfeeding should also be discontinued if the mother is treated on this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CIML NK cells and IL-2.
Trial design
Design model
Single group
Treatments tested in this trial
Cytokine-Induced Memory-like Natural Killer Cells
Biological/VaccineAllogeneic, cytokine induced memory-like natural killer cells, via intravenous infusion per protocol.
Interleukin-2
Biological/VaccineRecombinant, human glycoprotein, single-use 22 MIU vials, via subcutaneous (under the skin) injection per protocol.
Venetoclax
DrugSelective inhibitor of BCL-2 protein, 10, 50, or 100 mg tablets, via orally per standard-of-care.
Treatment groups
10 Participants
are divided into 2 treatment groupsGroup A: Cohort 1: Dose Level 0Experimental treatment 3 interventions
Group B: Cohort 1: Dose Level -1Experimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Dose Limiting Toxicity (DLT)
A DLT is defined as an adverse event (AE) that is related to the CIML NK cell infusion with venetoclax as consolidation therapy. Toxicities are to be assessed according to the CTCAEv5.
Time frame
Observing window is from Day 0 (day of CIML NK cell infusion) to Day +282
Maximum Tolerated Dose (MTD)
The MTD in the CIML NK cell infusion with venetoclax as consolidation therapy is determined by the number of participants who experience a DLT. See previous primary outcome measure for the DLT definition. If ≤1 DLTs are observed at dose-level 0, this dose will be the MTD. If ≥2 DLTs are observed in a cohort of 5 evaluable participants, then the MTD is considered exceeded. If this is dose level 0, dose de-escalation will take place, and 5 evaluable participants will be enrolled at dose level -1. If ≥2 DLTs are observed at dose level -1, accrual will stop.
Time frame
Observing window is from Day 0 (day of CIML NK cell infusion) to Day +28Secondary outcomes
1
Measurable Residual Disease Negative (MRD-) Rate
MRD- rate is defined as the proportion pf participants achieving MRD. MRD clearance is evaluated by both highly sensitive flow cytometry and duplex sequencing on paired bone marrow samples.
Time frame
At +28 days post CIML NK Infusion2
100-day Leukemia-Free Survival (LFS)
Leukemia free survival based on the Kaplan-Meier method is defined as the the duration of time from study entry to documented disease progression (leukemic relapse or death from any cause) or death. 100-day LFS is calculated from the KM curve with standard error.
Time frame
100 Days3
1-year Leukemia-Free Survival (LFS)
Leukemia free survival based on the Kaplan-Meier method is defined as the the duration of time from study entry to documented disease progression (leukemic relapse or death from any cause) or death. 1-year LFS is calculated from the KM curve with standard error.
Time frame
1 Year4
100-day Overall Survival (OS)
100-day OS is a probability estimated using the Kaplan-Meier method; OS is defined as the time from study entry to death, or censored at date last known alive.
Time frame
100 DaysSponsors and contacts
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Source ClinicalTrials.gov