Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions in Children and Young Adults With High Risk Acute Myeloid Leukemia Receiving Myeloablative HLA-Haploidentical Hematopoietic Cell Transplant (EXCEL)
Toshihiro Onishi, MD
Primary Investigator
Brief description of study
What is the purpose of this study?
This is a Phase II pilot study to determine the efficacy of three fixed dose (1 x 108/kg)usions of ex-vivo expanded human leukocyte antigen (HLA)-haploidentical donor natural killer (NK) cells (haploNK) in children and young adults with high risk acute myeloidukemia (AML) undergoing HLA-haploidentical hematopoietic cell transplant (haploHCT) with a busulfan and cyclophosphamide-based myeloablative conditioning regimen and post-transplantyclophosphamide (PTCy) for graft versus host disease (GVHD) prophylaxis. The investigators will also demonstrate the feasibility of performing this trial in a multi-center study. The investigators hypothesize that the infusion of haploNK in this setting will facilitateune reconstitution and decrease relapse rates and infectious complications withoutg GVHD, resulting in improved survival as compared to recent historical cohorts of haploHCT without NK cell infusion.
THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic.
Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office
Email: iutrials@iu.edu
Phone: (317) 278-5632
Detailed description of study
What will happen during the study?
- Peripheral blood (PB) ≤ 450 mL and based on donor weight (minimum 10 ml/kg) will be drawn from the HLA-haploidentical donor at least 16 days before the scheduled day of transplant (Day 0).
- HaploNK cells will be manufactured from the PB of the donor after co-culture with irradiated feeder cells (IFC) as described in Section 2.4.
- The recipients will receive three NK cell infusions on Day-1, Day+7 (± 1 day) and Day+42 (up to Day+90) from day of transplant (Day 0).
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Acute Myeloid Leukemia, Riley
-
Age: 25 years or below
-
Gender: All
Inclusion Criteria:
- Age ≤ 25 years at time of enrollment
- High-risk AML, as defined by one of the following:
- AML in CR1 (defined as <5% blasts in BM by morphology and flow cytometry) having athese high-risk features: i. Mutations associated with high risk disease(Appendix A). Other high-risk features not explicitly stated in Appendix A can bedered after discussion/approval with the protocol chair/team ii. MRD-positive athe end of Induction I chemotherapy (defined as flow cytometry ≥ 0.1% blasts) b. AML≥CR2 (defined by <5% blasts in BM by morphology and flow cytometry)
Recovery from prior cycle of chemotherapy as defined by an absolute neutrophil count ≥
500/mm3
- AML secondary to select germline marrow failure disorders (with exception of FanconiAnemia) may be eligible but require approval from Protocol Chairs prior to enrollment.
- Performance status ≥70% (Lansky for <16 years; Karnofsky for ≥16 years)
- Adequate major organ system function as demonstrated by:
- Renal: Creatinine clearance (CrCl) ≥60 mL/min/1.73m2 by Cockcroft-Gault formula,hwartz formula, or nuclear GFR study (Table 3)
- Hepatic: Total bilirubin <2 mg/dL (unless due to Gilbert syndrome) and ALT andAST < 5x ULN
- Cardiac: LVEF at rest ≥50% or SF ≥27% (by MUGA or ECHO)
- Pulmonary: DLCO, FEV1, and FVC ≥ 50% of predicted corrected for hemoglobin. For<7 years of age or those unable to perform PFTs: O2 Sat >92% on room airby pulse oximetry and on no supplemental O2 at rest
The patient, patient's parent, guardian, or legal representative can provide written
informed consent
Exclusion Criteria:
- Active extramedullary disease
- Unresolved/ongoing and serious viral, bacterial, or fungal infection despite
- Positive pregnancy test in a female of child-bearing potential (FCBP)
- Inability to comply with medical therapy or follow-up
- Prior allogeneic transplant
- Patients with Fanconi Anemia and Down syndrome
