NK Cell Therapy for Acute Myeloid Leukemia

Recruiting at 1 trial location

Overseen By Roman Shapiro, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must be taking: Interleukin-2

Must not be taking: Sirolimus, Steroids

Disqualifiers: HIV, Hepatitis B/C, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

15 Participants Needed

Trial Summary

What is the purpose of this trial?

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)

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that certain therapies, like BCR-ABL inhibitors, must be stopped at least 2 weeks before the NK cell infusion. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment Cytokine Induced Memory-like Natural Killer Cells for Acute Myeloid Leukemia?

Research shows that Cytokine Induced Memory-like Natural Killer Cells (CIML NK cells) have enhanced ability to fight leukemia cells and improve survival in animal models. In a clinical trial, these cells led to complete remission in some patients with acute myeloid leukemia, indicating promising results for this treatment. ^{1 2 3 4 5}

Is NK cell therapy safe for humans?

Research shows that using cytokine-induced memory-like (CIML) NK cells in cancer treatment, including for acute myeloid leukemia (AML), is considered safe and has resulted in promising outcomes. ^{2 5 6 7 8}

How is the NK Cell Therapy for Acute Myeloid Leukemia different from other treatments?

This treatment uses cytokine-induced memory-like natural killer (CIML NK) cells, which are enhanced by a brief preactivation with specific proteins (IL-12, IL-15, and IL-18) to improve their ability to fight leukemia cells. Unlike conventional treatments, these NK cells have a memory-like function that allows them to persist and remain active for a longer time, potentially leading to better outcomes in patients with acute myeloid leukemia. ^{1 2 3 4 9}

Research Team

Roman Shapiro, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults aged 60 or older with newly diagnosed acute myeloid leukemia (AML), those in first complete remission but still have detectable disease, and patients with secondary AML, therapy-related MDS/AML, or certain types of myelodysplastic syndrome (MDS). Participants must have acceptable bilirubin levels unless due to Gilbert's syndrome or hemolysis.

Inclusion Criteria

I have been diagnosed with MDS/MPN or CMML.

I have acute myeloid leukemia in first complete remission and minimal residual disease detected.

Total bilirubin: ≤1.5 x institutional upper limit of normal (ULN) (except Gilbert's or disease related hemolysis, then < 3 x ULN)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive standard-of-care conditioning chemotherapy and stem cell infusion followed by CIML NK cells and Interleukin-2 infusions

6 weeks

Multiple visits for infusions and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for GVHD and disease progression

1 year

Regular visits for assessments

Long-term Follow-up

Participants are monitored for long-term outcomes such as overall survival and progression-free survival

Up to 3 years

Treatment Details

Interventions

• Cytokine Induced Memory-like Natural Killer Cells
• Interleukin-2

Trial Overview The study tests CIML NK cell infusions combined with Interleukin-2 injections to prevent cancer relapse in patients who've had a stem cell transplant for AML, MDS, or overlap syndromes. It aims to determine the safety and effectiveness of this approach.

Participant Groups

Group I: Phase 1/1b: CIML NK Cells + Interleukin-2 Experimental Treatment 2 Interventions

5 eligible participants will be enrolled to determine the maximum tolerated dose (MTD) of CIML NK at starting dose level 0. * Screening and baseline visit with assessments and bone marrow aspirate and biopsy. * Day 0: Standard-of-care conditioning chemotherapy and stem cell infusion. * Day 7: Predetermined dose of CIML NK cells 1x daily. * Days 7, 9, 11, 13, 15: Predetermined dose of Interleukin-2 1x daily every other day (5 doses total). * Dose limiting toxicity period for 6 weeks after infusion of CIML NK cells If 0 or 1 dose limiting toxicity is observed at the dose level, then this dose will be the MTD and study will proceed to Phase 1b. De-escalation to dose level -1 per protocol if ≥2 DLTs occur with dose Level 0. In phase Ib, 10 additional participants will be enrolled at the maximum tolerated dose.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Findings from Research

Cytokine-induced memory-like NK cells show enhanced ability to produce interferon-γ and kill leukemia cells, making them a promising option for treating acute myeloid leukemia (AML).

In a first-in-human phase 1 clinical trial, memory-like NK cells were successfully expanded in AML patients, leading to clinical responses in five out of nine patients, including four complete remissions, indicating their potential effectiveness as an immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Romee, R., Rosario, M., Berrien-Elliott, MM., et al.[2021]

Cytokine-induced memory-like (CIML) NK cells, which are generated through brief stimulation with IL-12, IL-15, and IL-18, show enhanced effector functions and long-term persistence, making them promising candidates for cancer immunotherapy.

Clinical trials have demonstrated that infusions of CIML NK cells are safe and have led to complete clinical remissions in patients with relapse/refractory acute myeloid leukemia (AML).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications. Terrén, I., Orrantia, A., Astarloa-Pando, G., et al.[2022]

In a clinical trial involving 15 patients with relapsed/refractory acute myeloid leukemia (AML), the use of donor-derived memory-like (ML) NK cells combined with N-803 (an IL-15 superagonist) was well tolerated and resulted in an impressive 87% of patients achieving a composite complete response within 28 days.

The ML NK cells showed significant expansion and persistence, remaining the dominant lymphocyte population for over 2 months post-transplant, and exhibited enhanced antitumor functions compared to conventional NK cells, indicating their potential as an effective immunotherapy strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia. Berrien-Elliott, MM., Foltz, JA., Russler-Germain, DA., et al.[2023]

Genetically modifying cytokine-induced killer cells with anti-CD33 chimeric receptors significantly enhances their ability to kill acute myeloid leukemia cells, achieving up to 80% lysis in laboratory tests.

While these modified cells can also target normal hematopoietic progenitor cells, they still retain some ability to form colonies, indicating a potential balance between efficacy and safety in immunotherapy for leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-induced killer cells for cell therapy of acute myeloid leukemia: improvement of their immune activity by expression of CD33-specific chimeric receptors. Marin, V., Pizzitola, I., Agostoni, V., et al.[2021]

Natural killer (NK) cell-based immunotherapy shows promise in treating acute myeloid leukemia (AML) by targeting cancer cells and enhancing the immune response, particularly through the use of cytokine-induced memory-like (CIML) NK cells.

CIML-NK cells, which are pre-activated with specific cytokines, demonstrate a longer lifespan and adaptive immunity characteristics, making them a potentially effective and safe treatment option for AML, addressing the limitations of traditional NK cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-Induced Memory-Like NK Cells: Emerging strategy for AML immunotherapy. Bakhtiyaridovvombaygi, M., Yazdanparast, S., Mikanik, F., et al.[2023]

In a study involving 24 patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), the infusion of autologous cytokine-induced killer (CIK) cells did not show a survival benefit for AML patients post-transplant, nor did it significantly reduce detectable disease in CML patients.

The treatment was found to be safe, with only mild adverse reactions like fever reported, but the results suggest that further modifications to enhance the effectiveness of CIK cells are necessary for better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II clinical trial of autologous cytokine-induced killer cells as adjuvant immunotherapy for acute and chronic myeloid leukemia in clinical remission. Linn, YC., Yong, HX., Niam, M., et al.[2022]

Cytokine-induced killer (CIK) cells, derived from patients or healthy donors, show strong potential in targeting leukemia cells without harming normal hematopoietic stem cells, making them a promising option for leukemia treatment.

CIK cells can generate a graft versus tumor response while minimizing graft versus host disease, suggesting they could effectively prevent leukemia relapse after hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-induced killer cells: A novel immunotherapy strategy for leukemia. Yang, XY., Zeng, H., Chen, FP.[2020]

Cytokine-induced memory-like (CIML) NK cells, stimulated with IL-12/15/18, showed significantly enhanced characteristics such as increased expression of activating receptors and granzyme B, indicating their potential for improved immune responses against tumors and viral infections.

CIML NK cells demonstrated greater degranulation capacity and higher production of IFN-γ compared to control NK cells, suggesting they could be more effective in immunotherapy applications, with specific biomarkers identified for clinical relevance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function. Carreira-Santos, S., López-Sejas, N., González-Sánchez, M., et al.[2023]

Adoptive NK cell infusion using clinical-grade membrane-bound IL-21/4-1BBL-expanded NK cells showed significant antileukemic activity against acute myeloid leukemia (AML) in both laboratory and animal studies, with expanded NK cells persisting in the body for at least 13 days after infusion.

Patients with minimal residual disease (MRD+) who received NK cell treatment experienced better overall survival compared to those undergoing standard consolidation therapy, with no major adverse events reported, indicating a promising safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded clinical-grade membrane-bound IL-21/4-1BBL NK cell products exhibit activity against acute myeloid leukemia in vivo. Zhao, XY., Jiang, Q., Jiang, H., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia. [2023]

4. Italy pubmed.ncbi.nlm.nih.gov

Cytokine-induced killer cells for cell therapy of acute myeloid leukemia: improvement of their immune activity by expression of CD33-specific chimeric receptors. [2021]

5. France pubmed.ncbi.nlm.nih.gov

Cytokine-Induced Memory-Like NK Cells: Emerging strategy for AML immunotherapy. [2023]

6. England pubmed.ncbi.nlm.nih.gov

A phase I/II clinical trial of autologous cytokine-induced killer cells as adjuvant immunotherapy for acute and chronic myeloid leukemia in clinical remission. [2022]

7. Greece pubmed.ncbi.nlm.nih.gov

Cytokine-induced killer cells: A novel immunotherapy strategy for leukemia. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Expanded clinical-grade membrane-bound IL-21/4-1BBL NK cell products exhibit activity against acute myeloid leukemia in vivo. [2021]