Nivolumab for Acute Myeloid Leukemia

Recruiting at 49 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS involvement, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 92 weeks

82 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well nivolumab works in eliminating any remaining cancer cells and preventing cancer from returning in patients with acute myeloid leukemia that had a decrease in or disappearance of signs and symptoms of cancer after receiving chemotherapy. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the study drug. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Nivolumab for treating Acute Myeloid Leukemia?

Research shows that blocking PD-1 pathways, which Nivolumab does, can enhance the body's immune response against leukemia. In studies with similar drugs, this approach has shown potential in treating acute myeloid leukemia by reactivating the immune system to fight cancer cells. ^{1 2 3 4 5}

Is nivolumab generally safe for humans?

Nivolumab, also known as Opdivo, can cause immune-related adverse events (side effects where the immune system attacks normal cells) and hematological toxicities (blood-related side effects), which are rare but can be serious and life-threatening. ^{6 7 8 9 10}

How is the drug Nivolumab unique in treating acute myeloid leukemia?

Nivolumab is unique because it is an immune checkpoint inhibitor that blocks the PD-1 pathway, enhancing the body's immune response against leukemia cells, which is different from traditional chemotherapy that directly targets cancer cells. ^{1 4 5 11 12}

Research Team

Wendy Stock, MD

Principal Investigator

University of Chicago Comprehensive Cancer Center EDDOP

Eligibility Criteria

Adults with acute myeloid leukemia in remission after chemotherapy, not eligible for stem cell transplant due to age or other factors, and who haven't used certain immune-targeting drugs before. Participants must have adequate organ function, agree to use contraception, and not be pregnant or breastfeeding.

Inclusion Criteria

I am in remission from my last chemotherapy, confirmed by a biopsy within the last 60 days.

I am 18 years old or older.

I am fully active or able to carry out light work.

Exclusion Criteria

Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) might be enrolled if the viral load by PCR is undetectable with/without active treatment and absolute lymphocyte count >= 350/ul

I have not received treatments targeting immune checkpoints.

Patients who are receiving any other investigational agents

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive nivolumab intravenously every 2 weeks for up to 46 cycles or undergo standard of care observation

92 weeks

Bi-weekly visits for nivolumab group

Follow-up

Participants are monitored for progression free survival and overall survival after treatment

2 years

Periodic visits every 6 months for 1 year, then yearly

Treatment Details

Interventions

• Nivolumab

Trial Overview The REMAIN trial is testing if Nivolumab can prevent cancer from returning in patients whose acute myeloid leukemia has responded well to chemotherapy. It involves monitoring health signs, collecting biological samples, bone marrow biopsies, and heart scans.

Participant Groups

Group I: Arm I (nivolumab) Experimental Treatment 4 Interventions

Patients receive nivolumab IV over 60 minutes once every 2 weeks. Treatment repeats every 2 weeks for 46 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy at screening, months 3, 6, and 12, as clinically indicated, and during off-study evaluation. Patients also undergo collection of blood samples at screening, weeks 9, 13, 25, and 53, and during off-study evaluation or at time of clinically suspected relapse. Patients may undergo ECHO as clinically indicated.

Group II: Arm II (observation) Active Control 4 Interventions

Patients undergo standard of care clinical observation for up to 2 years. Upon disease relapse, patients may cross-over to Arm I. Patients also undergo bone marrow biopsy at screening, months 3, 6, and 12, as clinically indicated, and during off-study evaluation. Patients also undergo collection of blood samples at screening, weeks 9, 13, 25, and 53, and during off-study evaluation or at time of clinically suspected relapse. Patients may undergo ECHO as clinically indicated.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Immune checkpoint inhibitors alone have shown limited effectiveness in treating acute myeloid leukemia (AML), indicating that monotherapy may not be sufficient for this type of cancer.

Combining immune checkpoint inhibitors with hypomethylating agents appears to be a safe and potentially more effective approach, with ongoing clinical trials exploring these combinations to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors in Acute Myeloid Leukemia: Novel Combinations and Therapeutic Targets. Stahl, M., Goldberg, AD.[2020]

High expression levels of immune checkpoints PD-1, PD-L1, and PD-L2 in bone marrow cells of acute myeloid leukemia (AML) patients are associated with poor overall survival, based on analysis of RNA-seq and mutation data from 176 patients and validation in 62 additional patients.

Co-expression patterns of immune checkpoints, such as PD-1/CTLA-4 and PD-1/PD-L1, correlate with significantly lower survival rates, suggesting these patterns could serve as potential biomarkers for developing new therapies for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression patterns of immune checkpoints in acute myeloid leukemia. Chen, C., Liang, C., Wang, S., et al.[2021]

The addition of nivolumab to standard chemotherapy (idarubicin and cytarabine) in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome showed promising results, with a median overall survival of 18.54 months and a median relapse-free survival of 18.54 months after a median follow-up of 17.25 months.

The treatment was generally safe, with no treatment-related deaths attributed to nivolumab, although some patients experienced grade 3-4 immune-related adverse events, indicating that while the combination therapy is feasible, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a single-arm, phase 2 study. Ravandi, F., Assi, R., Daver, N., et al.[2020]

In a phase 1b/2 trial involving 19 patients with relapsed/refractory acute myeloid leukemia (AML), the combination of azacitidine and the anti-PD-L1 inhibitor avelumab was well tolerated but showed limited clinical activity, with an overall complete remission rate of only 10.5%.

Analysis of bone marrow blasts revealed significantly higher expression of PD-L2 compared to PD-L1, suggesting that PD-L2 may play a key role in the resistance to anti-PD-L1 therapy in AML, indicating a potential target for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b/2 study of azacitidine with PD-L1 antibody avelumab in relapsed/refractory acute myeloid leukemia. Saxena, K., Herbrich, SM., Pemmaraju, N., et al.[2022]

In a meta-analysis of five studies involving 2399 patients, nivolumab was found to significantly lower the risk of hematological toxicities such as anemia, neutropenia, and leukopenia compared to other treatments.

The relative risks for these conditions were notably low, indicating that nivolumab may be a safer option regarding hematological side effects, which is important for clinicians when considering treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. Shi, Z., Liu, X., Chen, M., et al.[2023]

In a study of 69 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab, those who experienced immune-related adverse events (irAEs) had significantly better overall survival (OS) and progression-free survival compared to those without irAEs, suggesting that irAEs may be a positive indicator of treatment response.

The study identified three key factors influencing OS: the presence of irAEs, C-reactive protein levels, and performance status, indicating that monitoring these factors could help predict patient outcomes in mRCC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Impact of Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab: A Multicenter Retrospective Study. Nukaya, T., Takahara, K., Yoshizawa, A., et al.[2023]

In a study of 35 patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab, 62.9% experienced immune-related adverse events, which were associated with significantly longer progression-free and overall survival rates.

The presence of immune-related adverse events, particularly skin reactions, was identified as an independent predictor of better clinical outcomes, suggesting that these events could serve as effective biomarkers for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. Ueda, K., Suekane, S., Kurose, H., et al.[2022]

In a study of 47 patients with metastatic renal cell carcinoma treated with nivolumab, 48.9% experienced immune-related adverse events (irAEs), with rash being the most common.

Patients who developed irAEs had significantly longer progression-free survival (13.1 months vs. 4.87 months) and overall survival (26.0 months vs. not reached) compared to those without irAEs, indicating that the presence of irAEs may be a positive prognostic factor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between immune-related adverse events and prognosis in patients with metastatic renal cell carcinoma treated with nivolumab. Ishihara, H., Takagi, T., Kondo, T., et al.[2020]

References

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

Immune Checkpoint Inhibitors in Acute Myeloid Leukemia: Novel Combinations and Therapeutic Targets. [2020]

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

Immune escape and immunotherapy of acute myeloid leukemia. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Expression patterns of immune checkpoints in acute myeloid leukemia. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a single-arm, phase 2 study. [2020]

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

A phase 1b/2 study of azacitidine with PD-L1 antibody avelumab in relapsed/refractory acute myeloid leukemia. [2022]

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

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. [2023]

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

Prognostic Impact of Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab: A Multicenter Retrospective Study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. [2022]

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

Association between immune-related adverse events and prognosis in patients with metastatic renal cell carcinoma treated with nivolumab. [2020]

10. Germany pubmed.ncbi.nlm.nih.gov

Outcomes associated with immune-related adverse events in metastatic non-small cell lung cancer treated with nivolumab: a pooled exploratory analysis from a global cohort. [2021]

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

Immune therapies in acute myeloid leukemia: a focus on monoclonal antibodies and immune checkpoint inhibitors. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Interferon-induced programmed death-ligand 1 (PD-L1/B7-H1) expression increases on human acute myeloid leukemia blast cells during treatment. [2017]