๐ฌIn plain words
What the trial is, and whether it could suit you
The purpose of this research study is to test the safety and efficacy of cytokine induced memory-like (CIML) natural killer (NK) cells expanded with Interleukin-2 (IL-2) at preventing relapse in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or MDS and myeloproliferative neoplasm (MPN) overlap syndrome after a standard-of-care stem cell transplant.
Names of the study therapies involved in this study are:
* CIML NK cells intravenous infusion (cellular therapy)
* Subcutaneous Interleukin-2 (recombinant, human glycoprotein)
Sign in to get the eligibility rules as simple questions to take to your doctor.
๐ Eligibility rules (as published)
Inclusion Criteria for Trial Enrollment:
* Histologically or cytologically confirmed diagnosis of AML, MDS, or MDS/MPN that is at high risk for post-transplant relapse and that has measurable disease prior to transplant. Patients at high risk for post-transplant relapse include:
* De novo AML diagnosed at or after age 60, except CBF AML
* De novo AML in CR1 AND MRD+ by Hematologics Inc. flow cytometry pretransplant (this would be on the most recent pre-transplant bone marrow)
* Secondary AML
* AML with 5 - \> 10% blasts at the time of transplant who are judged by their treating clinician and study PI to have no benefit from additional pre-transplant chemotherapy
* Any AML transplanted in CR2 or greater
* TP53-mutated MDS or AML
* Therapy-related MDS or AML
* MDS with monosomy 7
* MDS with \>= 5% blasts at the time of transplant
* MDS/MPN or CMML
* Adequate organ function within 2 weeks of NK cell infusion as defined below (should correspond with admission for SCT):
* Total bilirubin: โค1.5 x institutional upper limit of normal (ULN) (except Gilbert's or disease related hemolysis, then \< 3 x ULN)
* AST(SGOT)/ALT(SGPT): โค3 x institutional ULN
* Serum creatinine \</= 2.0mg/dL
* O2 saturation: โฅ90% on room air
* LVEF \>40%. If there is no clinical evidence of a change in cardiovascular function from the time of pre-transplantation ECHO (per FACT standards should be performed within 6 weeks of stem cell infusion), then there is no need to repeat it. Otherwise, an ECHO will need to be repeated.
* Adult patients (age โฅ 18) eligible for and planned to undergo a standard-of-care reduced intensity conditioning (RIC) HLA-matched related or related haploidentical allogeneic stem cell transplant using PTCY-based GVHD prophylaxis. All eligibility criteria and workups for undergoing SOC allogeneic SCT for the recipient and donor will be based on institutional standards and SOPs.
* For patients with AML, the disease must meet criteria for CR/Cri according to 2017 ELN guidelines, or have 5-10% blasts at the time of the transplant and in the judgement of their primary BMT clinician and study PI to have no benefit from additional pre-transplant chemotherapy. For patients with MDS or MDS/MPN, the blast percentage on the bone marrow aspirate and biopsy must be less than 10%.
* The same related donor is available to provide a non-mobilized apheresis product after the stem-cell donation.
* ECOG performance status \<= 2 (Karnofsky \>= 60%, see Appendix C).
* Negative pregnancy test for women of childbearing age
* The effects of CIML NK cells combined with 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 control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after IL-2 dose administration.
* No laboratory evidence of ongoing hemolysis in opinion of investigator
Exclusion Criteria Trial Enrollment:
* Adult participants who are eligible for and who would be expected to have a greater benefit from myeloablative conditioning in their SOC allo HSCT as judged by their treating physician
* Participants with mutations such as FLT3-ITD, IDH, or BCR-ABL mutations who are planned to receive targeted agent maintenance therapy to prevent relapse post-transplant are excluded.
* Extramedullary leukemia involving sanctuary sites not readily accessible to immune surveillance, such as CNS or testis. Other sites of extramedullary relapse (e.g., leukemia cutis, granulocytic sarcoma) are acceptable.
* The planned use of sirolimus for GVHD prophylaxis would result in exclusion of the patient from the study. Consideration of the addition of sirolimus to the GVHD prophylaxis regimen within the first 100 days after transplant must be reviewed with the study PI.
* Prior history of allogeneic stem cell transplant other than SOC alloHSCT referred to in this study taking place 7 days prior to CIML NK infusion.
* Prior history of solid organ (allograft) transplantation
* Prior history of allergic reactions to cellular products
* Uncontrolled concurrent illness such as ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric/social illness that would limit compliance with study requirements.
* 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. 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, breastfeeding should be discontinued if the mother is treated on this study.
* HIV-positive patients are excluded due to the potential for interaction between antiretroviral therapy as well as the risk for lethal infection in the context of marrow-suppressive therapy.
* Patients with active and uncontrolled Hepatitis B or C are ineligible due to the high risk of treatment-related hepatotoxicity after cellular 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. Diagnosed and treated within the past 2 years for: nonmetastatic melanoma, surgically resected (not needing systemic chemotherapy) squamous cell carcinoma of skin and nonmetastatic prostate cancer not needing systemic chemotherapy.
* History of allergic reactions attributed to compounds of similar chem