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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment to prevent relapse in individuals with certain blood cancers, such as acute myeloid leukemia (AML), following a stem cell transplant. The treatment combines cytokine-induced memory-like natural killer (CIML NK) cells with a protein called Interleukin-2. It targets those with AML, myelodysplastic syndrome (MDS), or related conditions who face a high risk of cancer returning after a stem cell transplant. Individuals diagnosed with these cancers and concerned about relapse after treatment might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Studies have shown that a special type of immune cells, called cytokine-induced memory-like (CIML) natural killer (NK) cells, can be created from donor cells and safely administered to patients. Research indicates that these NK cells effectively target acute myeloid leukemia (AML) cells. Most patients have received these infusions without serious issues.

Interleukin-2 (IL-2) has been used in various treatments, and research suggests it can be safely administered at certain doses. Some studies have examined IL-2 combined with chemotherapy and found it generally well-tolerated.

Since this trial is in an early stage, the researchers are still collecting safety data. Early phase trials primarily focus on ensuring safety and determining the best dose, so side effects are closely monitored. So far, both CIML NK cells and IL-2 have shown promise in previous studies for being safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for acute myeloid leukemia (AML) involve chemotherapy, targeted therapies, or stem cell transplants. However, the use of Cytokine Induced Memory-like Natural Killer (CIML NK) cells is unique because it leverages the body's immune system in a new way. These NK cells are engineered to remember and more effectively target leukemia cells. Researchers are excited because this approach could potentially enhance the immune response against AML, offering a powerful alternative to the more generalized and often harsh effects of traditional chemotherapy. Additionally, the combination with Interleukin-2 aims to boost the activity and proliferation of these NK cells, potentially increasing the treatment's effectiveness while minimizing side effects.

What evidence suggests that this trial's treatments could be effective for preventing relapse in acute myeloid leukemia?

Research has shown that a special type of immune cell, called cytokine-induced memory-like (CIML) natural killer (NK) cells, may help fight acute myeloid leukemia (AML). These cells can attack AML cells, even when other treatments have failed. In this trial, participants will receive CIML NK cells combined with Interleukin-2 (IL-2), which helps grow these NK cells, enhancing their ability to fight cancer. Studies suggest that CIML NK cells can be safely created from donor cells and administered to patients. While more research is needed, early results indicate that these cells might help prevent cancer recurrence after a stem cell transplant. ^{1 2 3 4 6}

Who Is on the Research Team?

Roman Shapiro, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5436500/

Cytokine-induced memory-like natural killer cells exhibit ... Using mass cytometry, we found that memory-like NK cell functional responses were triggered against primary AML blasts, regardless of killer ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01898793

NCT01898793 | Cytokine-induced Memory-like NK Cells in ... This phase I/2 trial studies the side effects and best dose of activated natural killer cells in treating patients with relapsed or refractory acute myeloid ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223015160

Review Cytokine‐Induced Memory‐Like NK Cells It is believed that Natural killer (NK) cells play an important role in immunological first-line defense, predicting cancerous cell response to immunotherapy, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05580601

Study Details | NCT05580601 | Cytokine-Induced Memory ... The objective of this study is to demonstrate that cytokine-induced memory-like natural killer cells can be generated from donor cells and infused safely into ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27655849/

Cytokine-induced memory-like natural killer cells ... - PubMed Using mass cytometry, we found that memory-like NK cell functional responses were triggered against primary AML blasts, regardless of killer ...

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04354025/

Clinical Trial: NCT04354025 This phase 2 clinical trial investigates the effectiveness of cytokine-induced memory-like natural killer (CIML NK) cells in combination with ...