Acute Myeloid Leukemia study: Interleukin-2 vs Venetoclax
Official title CIML NK Cells With Venetoclax for AML
ClinicalTrials.gov ID: NCT06152809
What this study is testing
What is Cytokine-Induced Memory-like Natural Killer Cells?
An investigational cellular therapy being studied for acute myeloid leukemia (AML).
Also referred to as CIML NK Cells.
Plain-language explanation of the investigational treatment. It is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- The study wants to see if giving cytokine‑induced memory‑like natural killer (CIML NK) cells together with IL‑2 and venetoclax is safe and may help treat AML that still has some disease after standard treatment.
- Who it's for
- It is looking for adults who have AML that still shows measurable disease or less than 20% cancer cells in the bone marrow after previous therapy.
- What's involved
- Participants will receive a short course of drugs that lower their immune cells, then an infusion of CIML NK cells, followed by IL‑2 and the drug venetoclax. They will have regular blood tests and visits to monitor safety and disease status.
- Time commitment
- The treatment period lasts about 4 weeks, with several clinic visits during and after the infusion to check safety and blood counts.
- Phase 1: an early, usually small safety study
- Time commitment: about 1 year
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- 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...
- 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...
- 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
- 2022 ELN adverse risk mutations: Any one of the following mutations: Mutated TP53, ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2
You likely can't join if
- for Trial Enrollment (Registration visit)
- Participants are excluded if they received prior allogeneic stem cell transplant ≤ 6 months ago or require immunosuppressive therapy for active GVHD...
- Persisting Grade \> 2 non hematologic toxicity related to prior therapy is excluded
- Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this...
- 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...
- HIV-positive participants are ineligible because of the potential for pharmacokinetic interactions with anti-retroviral agents used in this study.
See the full eligibility criteria
Who can join
- 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...
- 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
- 2022 ELN adverse risk mutations: Any one of the following mutations: Mutated TP53, ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2
- Additional mutations associated with acquired resistance to venetoclax: Mutated NRAS, KRAS, FLT3 ITD/TKD
- ECOG performance status ≤2 (see Appendix A)
- Direct bilirubin: ≤1.5 x institutional upper limit of normal (ULN) (except Gilbert's or disease-related hemolysis, then \< 3 x ULN)
- AST(SGOT)/ALT(SGPT): ≤3 x institutional ULN
- creatinine clearance ≥ 45 mL/min; calculated by the Cockcroft Gault formula
- oxygen saturation ≥ 90% on room air
- left ventricular ejection fraction ≥ 40%
- Negative pregnancy test for women of childbearing potential only.
- The effects of CIML NK cells and IL-2 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth...
- Participants with current symptoms of cardiac disease should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.
- Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or how well it works assessment of the investigational regimen are eligible...
- Ability to understand and the willingness to sign a written informed consent document. (Providing consents in as many languages as possible is encouraged)
- people must be able to swallow pills.
- No laboratory evidence of ongoing hemolysis in the opinion of investigator (demonstration of hemolysis should include a haptoglobin level that is below assay).
What rules you out
- for Trial Enrollment (Registration visit)
- 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...
- 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...
- 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...
- 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.
- HIV-positive participants are ineligible because of the potential for pharmacokinetic interactions with anti-retroviral agents used in this study.
- Individuals with active uncontrolled hepatitis B or C are ineligible as they are at high risk of lethal treatment-related hepatotoxicity after conditioning therapy.
- Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1. History of other malignancy and have had complete remission of disease for at least 2 years; 2.
- History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to IL-2 or other agents used in study.
- Participants who are receiving any other investigational agents for AML, MDS/AML, or GVHD.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia, or psychiatric illness/social...
- Prior history of Grade 2 or higher hemolytic anemia (≥ 2g decrease in hemoglobin plus laboratory evidence of hemolysis) from any cause. Inclusion Criteria to Start Investigational Treatment Plan (On Treatment visit)
- Patient was eligible for protocol per section 3.1.
- Participants must undergo a repeat bone marrow biopsy at Visit #2 to determine one of two scenarios below.
- MRD+ remission: Repeat bone marrow biopsy at this time shows a complete remission (CR) or complete remission with incomplete count recovery (CRi) or morphologic leukemia free state (MLFS) (\< 5% blasts) but with...
- Relapsed/refractory oligoblastic AML (5-19% blasts): Repeat bone marrow biopsy at this time shows 5-19% residual myeloblasts in the bone marrow by either bone marrow aspirate or core biopsy.
- Relapsed disease: Defined as the appearance of 5% or greater myeloblasts in the bone marrow or peripheral blood after achieving a CR, CRh, or CRi. There are no stipulations on prior therapies.
- Refractory disease: Defined as failure to achieve a CR, CRh, or CRi after ≥ 1 cycle of intensive chemotherapy with a cytarabine-containing regimen (e.g., 7+3, MEC, HIDAC, reinduction chemotherapy such as 5+2, etc.), ≥ 2...
- Confirmed haploidentical or fully HLA-matched related donor that is willing and eligible for non-mobilized collection must be confirmed by the time of Visit #2.
- ECOG performance status ≤2 (see Appendix A)
- Direct bilirubin: ≤1.5 x institutional upper limit of normal (ULN) (except Gilbert's or disease-related hemolysis, then \< 3 x ULN)
- AST(SGOT)/ALT(SGPT): ≤3 x institutional ULN
- creatinine clearance ≥ 45 mL/min; calculated by the Cockcroft Gault formula
- oxygen saturation ≥ 90% on room air
- No significant change in clinical status that would, in the opinion of the investigator, increase the risk of adverse events associated with CIML NK infusion, (e.g., symptomatic congestive heart failure, unstable...
- Negative pregnancy test for women of childbearing potential only.
- people must be able to swallow pills. Exclusion Criteria to Start Investigational Treatment Plan (On Treatment visit)
- No live vaccines within the last 6 months.
- No ongoing or active infections.
- Moderate/strong inhibitors of CYP3A except of antifungal medications (such as posaconazole, voriconazole) which the patient is on and the dose of venetoclax has already been adjusted.
- The presence of donor-specific antibodies (DSAs) with mean fluorescence intensity (MFI) \>1000 using a standard assay in people who do not receive a desensitization protocol prior to and during stem cell transplant.
- Direct bilirubin: ≤ 1.5 x institutional upper limit of normal (ULN) (except Gilbert's or disease-related hemolysis, then \< 3 x ULN)
- AST (SGOT)/ALT (SGPT): ≤ 3 x institutional ULN
- No significant change in clinical status that would, in the opinion of the investigator, increase the risk of adverse events associated with lymphodepletion, (e.g., significant hypoxemia, symptomatic congestive heart...
- No evidence of active, uncontrolled infection. Patients receiving antibiotics for an infection may be treated if they have clinically responded to antibiotics.
- No live vaccines within the last 6 months Criteria to Receive CIML NK Infusion
- Direct bilirubin: ≤1.5 x institutional upper limit of normal (ULN) (except Gilbert's or disease-related hemolysis, then \< 3 x ULN)
- AST(SGOT)/ALT(SGPT): ≤3 x institutional ULN
- Creatinine clearance ≥ 45 mL/min; calculated by the Cockcroft Gault formula
- No Grade ≥3 non-hematologic toxicities of cyclophosphamide and fludarabine conditioning (except for Grade 3 nausea, vomiting, diarrhea, or constipation).
- No significant change in clinical status that would, in the opinion of the investigator, increase the risk of adverse events associated with CIML NK infusion, (e.g., significant hypoxemia, symptomatic congestive heart...
- No evidence of active, uncontrolled infection. Patients receiving antibiotics for an infection may be treated if they have clinically responded to antibiotics.
- No systemic steroid therapy (oral or IV) of \> 10mg prednisone or equivalent dose of other steroid agent on the day of NK cell infusion If any of the above criteria are noted at these time points, please discuss with PI...
- Total bilirubin: ≤1.5 x institutional upper limit of normal (ULN) (except Gilbert's or disease-related hemolysis, then \< 3 x ULN)
- AST(SGOT)/ALT(SGPT): ≤3 x institutional ULN
- No Grade ≥3 non-hematologic toxicities of cyclophosphamide and fludarabine conditioning (except for Grade 3 nausea, vomiting, diarrhea, or constipation).
- No significant change in clinical status that would, in the opinion of the investigator, increase the risk of adverse events associated with venetoclax administration, (e.g., significant hypoxemia, symptomatic...
- No evidence of active, uncontrolled infection. Patients receiving antibiotics for an infection may be treated if they have clinically responded to antibiotics.
- No live vaccines within the last 6 months
The study team makes the final eligibility decision.
Where it is enrolling
- Boston, Massachusetts, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part, but confirm specifics with the study team.
How long does this study last?
The study runs about 1 year per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
This study is enrolling now at Boston, Massachusetts, United States. Enter your location above to see the nearest enrolling site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from ClinicalTrials.gov. The study team decides eligibility, and your own doctor gives medical advice.