NK Cells + Atezolizumab for Acute Myeloid Leukemia

Recruiting at 6 trial locations

Overseen By Brian Shaffer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Antibiotics

Disqualifiers: CNS leukemia, Cardiovascular disease, Autoimmune disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for people with acute myeloid leukemia (AML) that has returned or resisted treatment. It combines a drug called atezolizumab with special immune cells, known as CIML-NK cell therapy, to determine if this mix can be given safely and effectively combat the cancer. The trial seeks individuals with AML who have tried other treatments without success or whose cancer returned within six months. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications for the trial?

The trial requires that you stop any systemic immune suppression medications at least 4 weeks before starting the study. If you're on therapeutic anticoagulation, your regimen must be stable for 2 weeks before enrolling. Additionally, any experimental biological treatments must be stopped for at least 5 half-lives before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that a type of immune cell treatment called cytokine-induced memory-like natural killer (CIML-NK) cells is safe for treating cancer. Patients with acute myeloid leukemia (AML) received these cells without major problems, and in some cases, the cancer temporarily disappeared.

Atezolizumab, the other treatment in this trial, has been tested with other drugs for AML. Research has shown it is generally safe, but results have been mixed. Some studies found that atezolizumab alone did not provide strong benefits, and there were concerns about side effects.

Overall, both CIML-NK cells and atezolizumab have been tested in people before, showing some safety and effectiveness, especially when used together for AML. However, like any treatment, there can be risks, and these studies aim to find the safest dose. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for acute myeloid leukemia, which often include chemotherapy and targeted therapy, this new approach combines Atezolizumab with CIML-NK cell therapy. Atezolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. CIML-NK cells, or Cytokine Induced Memory-Like Natural Killer cells, are designed to remember and attack cancer cells more effectively. This combination aims to boost the body's natural defenses against leukemia, potentially offering a more precise and powerful attack on cancer cells than existing treatments. Researchers are excited because this strategy might enhance the immune response and lead to better outcomes for patients.

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

This trial will examine the combination of cytokine-induced memory-like (CIML) natural killer (NK) cells with Atezolizumab for treating acute myeloid leukemia (AML). Studies have shown that CIML-NK cells can benefit individuals with relapsed or hard-to-treat AML, with some patients achieving complete remission. Atezolizumab, a drug that aids the immune system in fighting cancer, has undergone testing with other AML treatments. Researchers aim to determine how it might enhance the immune system's ability to combat cancer when combined with CIML-NK cells. Although the safety and effectiveness of Atezolizumab for AML remain under investigation, using it with CIML-NK cells in this trial could enhance its benefits. Current research suggests this combination might offer a promising new approach to treating AML. ^{2 6 7 8 9}

Who Is on the Research Team?

Brian Shaffer, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with relapsed/refractory acute myelogenous leukemia (AML) who have tried at least two prior treatments without success, including specific drugs if they have certain mutations. Participants must be in good physical condition and have a related donor for cell therapy.

Inclusion Criteria

Patients must meet specific laboratory criteria including serum bilirubin, AST and ALT levels, and creatinine clearance

Timing of treatment relative to prior therapies must meet specific criteria

I haven't taken any immune-suppressing drugs in the last 4 weeks.

Exclusion Criteria

I have a serious heart condition.

I have a history of specific lung conditions.

I do not meet the age and organ function requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-conditioning Chemotherapy

Participants receive a standard lymphodepleting regimen including fludarabine and cyclophosphamide prior to the infusion of CIML-NK cells

5 days

Daily visits for chemotherapy administration

Treatment

Participants receive CIML-NK cells infusion and a single dose of atezolizumab, followed by subcutaneous rh-IL2 every other day for 6 doses

2 weeks

Multiple visits for infusion and rh-IL2 administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• CIML-NK cell therapy

Trial Overview The study tests the highest dose of CIML-NK cell therapy combined with Atezolizumab that's safe for people with AML. It aims to determine mild side effects and effectiveness against cancer.

How Is the Trial Designed?

Group I: Cytokine Induced Memory-Like Natural Killer Cells Combined with Atezolizumb Experimental Treatment 3 Interventions

Pre-conditioning chemotherapy will consist of a standard lymphodepleting regimen including fludarabine 25 mg/m2 IV daily x 5 on days -6 to - 2 and cyclophosphamide 50 mg/kg IV x 2 on days -5 and -4 prior to the infusion of the CIML-NK cells. Standard MSKCC supportive care guidelines for infusion of chemotherapy including cyclophosphamide will be employed. On the day of infusion subjects will receive a single dose of atezolizumab IV over 60 minutes IV. Subjects will receive subcutaneous recombinant human IL-2 (rh-IL2) every other day x 6 doses beginning on day 0 via subcutaneous injection.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03154827

Safety, Tolerability and Efficacy of the BL-8040 and ... This study will assess the safety and effectiveness of a combination of BL-8040 and atezolizumab to find out what is the Safety, Tolerability and Efficacy of ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35491816/

A phase 1b study of atezolizumab in combination with ... Fourteen of the 16 patients (87.5%) died during the trial period due to disease progression (8/14) or AEs (6/14), hence the study was terminated ...

3. ashpublications.org ashpublications.org/thehematologist/article/doi/10.1182/hem.V14.5.7585/462928/The-Potential-Utility-of-Immunotherapy-for-AML

The Potential Utility of Immunotherapy for AML This study is a phase Ib, nonrandomized, open-label trial of the safety of combining the anti-PD-L1 antibody atezolizumab with the novel ...

4. tandfonline.com tandfonline.com/doi/abs/10.1080/10428194.2022.2057484

A phase 1b study of atezolizumab in combination with ... All patients reported at least 1 AE; 15 patients (93.8%) reported grade ≥ 3 AEs, and 15 patients (93.8%) reported SAEs. Fourteen of the 16 patients (87.5%) died ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121042944

Gilteritinib Can be Safely Combined with Atezolizumab for ... Results: As of 13 June 2021, 3 patients received gilteritinib 120 mg/day + atezolizumab 420 mg Q2W (cohort 1) and 8 patients received ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03922477

NCT03922477 | A Study Evaluating the Safety and ... This Phase Ib study is designed to evaluate the safety and pharmacokinetics of atezolizumab when given in combination with Hu5F9-G4 to patients with relapsed or ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9772102/

Safety, outcomes and T cell characteristics in patients with ... Notably, ASXL1 mutations were also associated with improved survival in a study of patients with relapsed and refractory acute myeloid leukemia (AML) treated ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02892318

NCT02892318 | A Study Evaluating the Safety and ... If the combination of atezolizumab and guadecitabine is found to be safe and tolerable in Cohort A1, Cohort A3 will assess the safety and tolerability of the ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2473952921008648

Atezolizumab alone or in combination did not demonstrate ... The high death rate and poor efficacy observed in this study do not support a favorable risk-benefit profile for atezolizumab as a single agent ...