Pembrolizumab + Chemotherapy for Acute Myeloid Leukemia

Recruiting at 10 trial locations

Overseen By Amer Zeidan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Anthracyclines, Anti-PD-1

Disqualifiers: Active malignancy, FLT3-mutated AML, 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

Compensation: Varies

Number of Visits: 10

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well cytarabine and idarubicin or daunorubicin with or without pembrolizumab work in treating patients with newly-diagnosed acute myeloid leukemia. Chemotherapy drugs, such as cytarabine, idarubicin, and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving induction chemotherapy with pembrolizumab may work better than induction chemotherapy alone in treating patients with acute myeloid leukemia.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, hydroxyurea must be stopped the day before starting chemotherapy, and corticosteroids are generally not allowed unless they are low doses for non-cancer conditions. It's best to discuss your specific medications with the trial team.

Is the combination of Pembrolizumab and chemotherapy safe for treating acute myeloid leukemia?

The combination of pembrolizumab and high-dose cytarabine has been studied in patients with relapsed or refractory acute myeloid leukemia, showing that serious immune-related side effects were rare and usually resolved on their own. Other studies involving idarubicin and cytarabine, which are part of the chemotherapy regimen, have shown that while effective, there can be significant toxicity, including some cases of treatment-related deaths. ^{1 2 3 4 5}

What makes the drug combination of Pembrolizumab and chemotherapy unique for treating acute myeloid leukemia?

This treatment combines pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with chemotherapy drugs like cytarabine and daunorubicin, which kill cancer cells directly. This combination aims to enhance the immune response against leukemia, potentially improving outcomes for patients with relapsed or refractory acute myeloid leukemia. ^{2 6 7 8 9}

Research Team

Amer M. Zeidan

Principal Investigator

Yale University Cancer Center LAO

Eligibility Criteria

Adults aged 18-75 with newly diagnosed acute myeloid leukemia (AML) can join this trial. They must be healthy enough for intensive chemotherapy, have good organ function, and not have other active cancers or certain blood disorders. Pregnant women and those with a history of severe allergies to study drugs are excluded.

Inclusion Criteria

I am using hydroxyurea or leukapheresis for high white blood cell count.

I am between 18 and 75 years old.

I've used hydroxyurea or leukapheresis for high white blood cell count but can stop hydroxyurea before starting chemotherapy.

Exclusion Criteria

I do not have active brain tumors or cancer in the lining of my brain.

I haven't had chemotherapy or radiotherapy in the last 4 weeks.

I have an active tuberculosis infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Patients receive cytarabine and idarubicin or daunorubicin, with pembrolizumab added in Arm I, to achieve complete remission or incomplete recovery.

28-35 days per cycle

Multiple visits for IV administration

Consolidation

Patients receive high-dose cytarabine and pembrolizumab in Arm I, or high-dose cytarabine alone in Arm II, to maintain remission.

28-42 days per cycle

Multiple visits for IV administration

Maintenance

In Arm I, patients receive pembrolizumab every 3 weeks for up to 2 years to maintain remission.

Up to 2 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 5 years

Every 6 months

Treatment Details

Interventions

• Cytarabine
• Daunorubicin Hydrochloride
• Idarubicin Hydrochloride
• Pembrolizumab

Trial Overview The trial is testing if adding pembrolizumab, an immune system booster, to standard AML chemotherapy (cytarabine and idarubicin or daunorubicin) is more effective than chemo alone in treating patients who are new to treatment.

Participant Groups

Group I: Arm I (cytarabine, idarubicin, daunorubicin, HSCT) Experimental Treatment 12 Interventions

See Detailed Description.

Group II: Arm II (cytarabine, idarubicin, daunorubicin, HSCT) Active Control 11 Interventions

See Detailed Description.

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

Approved in United States as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia
• Meningeal leukemia

Approved in European Union as Depocyt for:

• Lymphomatous meningitis

Approved in Canada as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 43 patients under 60 years old with untreated acute myeloid leukemia, the combination of idarubicin, etoposide, and carboplatin achieved a remission rate of 67% with a median leukemia-free survival of 15.4 months.

The treatment was associated with significant mucosal toxicity, including severe gastrointestinal side effects in a substantial number of patients, indicating that while effective, the regimen's tolerability may need improvement through adjustments in postremission therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remission induction therapy of untreated acute myeloid leukemia using a non-cytarabine-containing regimen of idarubicin, etoposide, and carboplatin. Bow, EJ., Gallant, G., Williams, GJ., et al.[2015]

In a study of 52 patients under 55 with acute myeloid leukemia (AML), the chemotherapy regimen BF12 led to a high remission rate of 78.4%, demonstrating its efficacy in treating newly diagnosed AML.

The same regimen also showed effectiveness in relapsed acute leukemia, with 65% of patients achieving complete remission, although some patients experienced toxicity-related deaths, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idarubicin, high-dose cytarabine, and etoposide for induction of remission in acute leukemia. Mehta, J., Powles, R., Singhal, S., et al.[2013]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a phase 1b study involving 28 patients with myelodysplastic syndromes (MDS) resistant to hypomethylating agents, pembrolizumab demonstrated manageable safety, with 36% experiencing treatment-related adverse events, but no patients achieved a complete or partial response.

Despite the lack of significant tumor response, 19% of patients showed a complete response in bone marrow, and the median overall survival was 6 months, indicating some clinical activity in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for myelodysplastic syndromes after failure of hypomethylating agents in the phase 1b KEYNOTE-013 study. Garcia-Manero, G., Ribrag, V., Zhang, Y., et al.[2022]

Pembrolizumab (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

References

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

Remission induction therapy of untreated acute myeloid leukemia using a non-cytarabine-containing regimen of idarubicin, etoposide, and carboplatin. [2015]

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

Phase II Trial of Pembrolizumab after High-Dose Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia. [2022]

3. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety analysis of different dose idarubicin plus cytarabine regimen as induction chemotherapy for young patients with de-novo acute myeloid leukemia]. [2020]

4. China pubmed.ncbi.nlm.nih.gov

[A Retrospective Study on the Efficacy and Safety of Idarubicin Combined with High-Dose Cytarabine Consolidation in Patients with Acute Myeloid Leukemia over 60 Years of Age in First Remission]. [2023]

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

Idarubicin, high-dose cytarabine, and etoposide for induction of remission in acute leukemia. [2013]

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

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

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

Pembrolizumab for myelodysplastic syndromes after failure of hypomethylating agents in the phase 1b KEYNOTE-013 study. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. [2022]

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

Safety and Efficacy of Pembrolizumab Prior to Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia. [2023]