Infusion of expanded NK cells to reduce relapse after stem cell transplant

Non-feeder Cell ex Vivo Expanded Allogeneic NK Cells Infusion Decrease Relapse Post Hematopoietic Stem Cell Transplantation.

This study is testing if giving special immune cells after a stem cell transplant can help people with blood cancers stay healthy and reduce the chances of their cancer coming back.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Sichuan University (Academic / other)
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT05250362 on ClinicalTrials.gov

What this trial studies

This phase I/II study evaluates the safety and effectiveness of infusing natural killer (NK) cells after hematopoietic stem cell transplantation in patients with hematologic malignancies. The NK cells are expanded outside the body using a non-feeder cell regimen to minimize risks associated with feeder cell infusion. The infusion occurs following myeloablative conditioning therapy, aiming to decrease the chances of relapse, severe graft versus host disease, and viral reactivation, thereby potentially improving survival rates for participants.

Who should consider this trial

Good fit: Ideal candidates include patients with hematologic malignancies who have a haploidentical donor and meet specific disease criteria.

Not a fit: Patients without a suitable haploidentical donor or those with non-hematologic malignancies may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce relapse rates and improve survival outcomes for patients undergoing stem cell transplantation.

How similar studies have performed: While the approach of using NK cells in this context is promising, it is still relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Patient with no matched related donor who has a related haploidentical donor identified (=\< 7/8 allele match at the A, B, C, DR loci) who is willing to undergo a bone marrow harvest and an NK cell collection approximately 2 weeks of the recipient's admission for transplant; the donor must be 16 years of age or older and weigh at least 50kg.
2. Patients with one of the following diseases: acute myeloid leukemia (AML): a. first complete remission with high-risk features defined as (i) greater than 1 cycle of induction therapy required to achieve remission; (ii) preceding myelodysplastic syndrome (MDS); (iii) presence of FLT3 mutations or internal tandem duplication or other mutations associated with poor-risk AML (e.g., DNMT3A, TET2); (iv) French-American-British Classification (FAB) M6 or M7 classification; (v) adverse cytogenetics: -5, deletion (del) 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 or complex karyotype (\> 3 abnormalities); (vi) treatment-related AML, or b. second or more significant remission; patients beyond the second remission have to be in complete remission (CR) at transplant to be eligible, or c. primary induction failure with partial response to therapy who achieve adequate cytoreduction
3. Patients with myelodysplastic syndromes (MDS): a. de novo MDS with intermediate or high-risk International Prognostic Scoring System (IPSS) scores; patients with intermediate-1 features should have failed to respond to hypomethylating agent therapy or b. patients with treatment-related MDS
4. Chronic myeloid leukemia (CML): a. failed to achieve cytogenetic remission or have a cytogenetic relapse after treatment with at least 2 tyrosine kinase inhibitors, or b. accelerated phase or blast phase at any time
5. Lymphoma: a. refractory to or released from 1st line therapy, salvaged by 2nd line therapy, or b. high-risk lymphoma with CR to 1st line therapy.
6. Performance score of at least 70% by Karnofsky or 0 to 1 by Eastern Cooperative Oncology Group (ECOG) (age \>= 12 years), or Lansky Play-performance scale of at least 70% or greater (age \< 12 years)
7. Serum creatinine clearance equal to or more than 50 ml/min (calculated with Cockcroft-Gault formula)
8. Bilirubin equal or less than 1.5 mg/dl except for Gilbert's disease Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or less than 200 IU/ml for adults
9. Conjugated (direct) bilirubin less than 2 x upper limit of normal
10. Left ventricular ejection fraction equal to or greater than 40%
11. Diffusing capacity of the lung for carbon monoxide (DLCO) equal or greater than 50% predicted corrected for hemoglobin; for children =\< 7 years of age who are unable to perform pulmonary function tests (PFT), oxygen saturation \>= 92% on room air by pulse oximetry

11. Patient or patient's legal representative, parent(s), or guardian should provide written informed consent; the permission of a minor if participant's age is at least seven and less than eighteen years

Exclusion Criteria:

1. Human immunodeficiency virus (HIV) positive; active hepatitis B or C
2. Uncontrolled infections; principal investigator (PI) is the final arbiter of this criterion Liver cirrhosis
3. Central nervous system (CNS) involvement within three months
4. Positive pregnancy test in a woman with childbearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
5. Inability to comply with medical therapy or follow-up

Where this trial is running

Chengdu, Sichuan

• West China Hospital of Sichuan University — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: Jie Ji, MD — West China Hospital, Sichuan Uiversity
• Study coordinator: Jie Ji, MD

Conditions Hematologic Malignancy; NK cell; stem cell transplant; relapse