Pembrolizumab + Chemotherapy for Acute Myeloid Leukemia

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of certain chemotherapy drugs, with or without pembrolizumab (an immunotherapy drug), in treating newly-diagnosed acute myeloid leukemia (AML). Chemotherapy aims to kill cancer cells or prevent their spread, while pembrolizumab may help the immune system target and attack the cancer. Participants recently diagnosed with AML who have not received extensive prior treatment might be suitable for this study. The trial examines whether combining chemotherapy with pembrolizumab is more effective than chemotherapy alone. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important advancements in AML treatment.

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

Research has shown that adding pembrolizumab to chemotherapy is generally safe for patients with acute myeloid leukemia (AML). In earlier studies, patients who received pembrolizumab with high-dose chemotherapy experienced manageable side effects. The most common side effects were tiredness and fever, but these were not severe for most individuals.

The chemotherapy drugs used in the trial—cytarabine, idarubicin, and daunorubicin—are standard treatments for AML and have well-known safety records. These drugs can cause side effects like nausea, hair loss, and low blood cell counts, but doctors effectively manage these issues.

The trial is in Phase 2, indicating that earlier research has shown the treatment to be somewhat safe. Phase 2 trials assess how well patients handle the treatment. So far, the combination of pembrolizumab with chemotherapy appears safe and well-tolerated by many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for acute myeloid leukemia (AML), which typically involve chemotherapy drugs like cytarabine, daunorubicin, and idarubicin, the study drug pembrolizumab brings a fresh approach by targeting the immune system. Pembrolizumab is an immune checkpoint inhibitor that works by blocking the PD-1 pathway, potentially allowing the body's immune system to better recognize and attack cancer cells. Researchers are excited about pembrolizumab because it offers a novel mechanism of action that could enhance the effectiveness of conventional chemotherapy, potentially leading to improved outcomes for patients with AML.

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

Research has shown that pembrolizumab, a medicine that aids the immune system, has potential in treating acute myeloid leukemia (AML). In earlier studies, patients with AML that did not respond to treatment or relapsed experienced benefits when pembrolizumab followed high-dose chemotherapy. Specifically, some patients achieved long-lasting remissions when using pembrolizumab as ongoing therapy after chemotherapy. In this trial, some participants will receive chemotherapy drugs like cytarabine, idarubicin, and daunorubicin, which are well-known for killing cancer cells or stopping their growth. Combining pembrolizumab with these chemotherapy drugs might enhance treatment effectiveness by boosting the immune system's ability to fight cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Amer M. Zeidan

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

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

My heart health is assessed to be at low to moderate risk.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8580622/

Phase II Trial of Pembrolizumab after High-Dose ... Immune-checkpoint blockade with pembrolizumab was tolerable and feasible after high-dose cytarabine in R/R AML, with encouraging clinical activity, particularly ...

2. unclineberger.org unclineberger.org/news/immunotherapy-after-high-dose-chemotherapy-leads-to-favorable-outcomes-in-acute-myeloid-leukemia/

Immunotherapy after high-dose chemotherapy leads to ... Researchers report clinical trial outcomes that benefited patients with resistant or relapsed acute myeloid leukemia.

3. haematologica.org haematologica.org/article/view/haematol.2024.285313

A phase II study of post-remission therapy with ... Pembrolizumab maintenance therapy is feasible and, when used with consolidation therapy, can result in durable remissions in select patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8753450/

Pembrolizumab and decitabine for refractory or relapsed ... The feasibility of the first-in-human combination of pembrolizumab and decitabine in adult patients with refractory or relapsed AML (R-AML).

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02708641

A Phase II Study of Pembrolizumab as Post-Remission ... This study evaluates the effect of pembrolizumab on the duration of remission in acute myeloid leukemia. Pembrolizumab is given after complete remission is ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/736/531082/Efficacy-and-Safety-of-Pembrolizumab-Added-to

Efficacy and Safety of Pembrolizumab Added to Azacitidine ... Pts who received any treatment dose on trial were evaluable for safety and efficacy analyses (N=58). The most frequent treatment-related AEs ( ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04214249?tab=table

NCT04214249 | BLAST MRD AML-1: BLockade of PD- ... This phase II trial studies how well cytarabine and idarubicin or daunorubicin with or without pembrolizumab work in treating patients with newly-diagnosed ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2666636721011714

Safety and Efficacy of Pembrolizumab Prior to Allogeneic ... One-year survival was not significantly different between the treatment groups (67% versus 78%; P = .34). 100-day mortality was 0% in the ICI group versus 17% ...