BLockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia 1 (BLAST MRD AML-1): A Randomized Phase 2 Study of the Anti-PD-1 Antibody Pembrolizumab in Combination With Conventional Intensive Chemotherapy as Frontline Therapy in Patients With Acute Myeloid Leukemia

Plain English Summary

BLAST MRD AML-1: BLockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia 1- A Randomized Phase 2 Study of Anti-PD-1 Pembrolizumab in Combination With Intensive Chemotherapy as Frontline Therapy in Patients With Acute Myeloid Leukemia is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Acute Myeloid Leukemia Post Cytotoxic Therapy, Secondary Acute Myeloid Leukemia. This trial tests if adding a drug called pembrolizumab to standard chemotherapy can help eliminate remaining cancer cells after treatment for newly diagnosed Acute Myeloid Leukemia (AML). It is for adults aged 18-75 with newly diagnosed AML who are eligible for intensive chemotherapy. Participation involves receiving standard chemotherapy (cytarabine and either idarubicin or daunorubicin) with or without pembrolizumab, and undergoing regular medical assessments, including blood and bone marrow tests. Standard treatment for AML typically involves intensive chemotherapy; this trial explores an enhanced approach. The trial aims to enroll 49 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 to 75 years with newly diagnosed Acute Myeloid Leukemia (AML). Patients must be eligible for intensive chemotherapy ('7+3' regimen). Certain prior treatments for related conditions (like myelodysplastic syndrome) are allowed, but AML must be previously untreated except for specific emergency measures. Patients with specific genetic abnormalities (like core-binding factor abnormalities) will be assigned to treatment groups based on these findings. This trial is studying Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Acute Myeloid Leukemia Post Cytotoxic Therapy, Secondary Acute Myeloid Leukemia, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures assess how effectively the treatment eliminates cancer cells to undetectable levels (MRD-negative complete response), which is crucial for long-term remission. The specific primary outcome measures are: Rate of Minimal Residual Disease (MRD) Negative - Complete Response (CR)/Complete Remission With Incomplete Recovery (CRi) (78 days (mean)); Rate of MRD-negative CR (33 days (mean)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to improve outcomes for newly diagnosed AML patients by targeting measurable residual disease, a key factor in relapse, with the addition of immunotherapy to standard chemotherapy. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Acute Myeloid Leukemia Post Cytotoxic Therapy, Secondary Acute Myeloid Leukemia, where improved treatment options are needed.

Investor Insight

This trial investigates a novel combination therapy for a significant cancer indication, potentially offering a new standard of care and representing an investment in advanced immunotherapy for hemato Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific chemotherapy drugs used, the potential benefits and risks of adding pembrolizumab, and what to expect during treatment. Participation involves regular clinic visits for chemotherapy infusions, blood draws, bone marrow tests, and imaging scans. Be prepared for potential side effects of chemotherapy and immunotherapy, and discuss any concerns with your healthcare team. The trial is being conducted at 10 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 49 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo collection of blood
• PROCEDURE: Bone Marrow Aspiration — Undergo bone marrow aspiration
• PROCEDURE: Bone Marrow Biopsy — Undergo bone marrow biopsy
• PROCEDURE: Computed Tomography — Undergo CT
• DRUG: Cytarabine — Given via continuous IV infusion

Primary Outcomes

• Rate of Minimal Residual Disease (MRD) Negative - Complete Response (CR)/Complete Remission With Incomplete Recovery (CRi) (78 days (mean))
• Rate of MRD-negative CR (33 days (mean))

Secondary Outcomes

• Rate of CR/CRi (33 days (mean) post induction)
• MRD Negativity (At day 14)
• Percentage of Patients With MRD-CR Using a MRD Cutoff of 0.01% (33 days (mean))
• Event-free Survival (From randomization to failure to achieve CR/CRi, relapse or death from any cause, 157 days (mean))
• Relapse-free Survival (RFS) (From first documentation of CR/CRi to either disease relapse or death from any cause, 33 days (mean))

Full Eligibility Criteria

Inclusion Criteria:

* Newly diagnosed and pathologically-confirmed AML, confirmed by a bone marrow aspirate and/or biopsy and/or peripheral blood with \>= 20% myeloid blasts. Bone marrow biopsy, or aspirate or peripheral blood that were obtained up to 3 weeks before signing consent are allowed for purposes of confirming AML diagnosis for eligibility purposes. Secondary AML (that is arising from prior myelodysplastic syndrome \[MDS\] as well as therapy-related \[t\]-AML) are also allowed. Clarifications: AML arising from myeloproliferative neoplasms (MPN), MPN/MDS overlap (including chronic myelomonocytic leukemia \[CMML\]) or another myeloid malignancy are NOT allowed. Note 1: Patients must have evidence of bone marrow involvement on aspirate or biopsy. Patients with only extramedullary disease and no bone marrow involvement will be excluded. Note 2: Every effort should be made to get an aspirate for central flow assessment at screening and all subsequent required time points, but in cases where an aspirate cannot be collected-including dry taps-the patient will not be excluded and assessments will be performed on peripheral blood (PB) which should be collected at every time that bone marrow (BM) is collected. Note 3: Some patients with AML require initiation of therapy quickly after diagnosis, and full metaphase karyotype results in some centers can take 2-3 weeks to result. To avoid this issue being an impediment to accrual to study or to cause delays in initiation of therapy in patients who need fast initiation of therapy, we allow use of karyotype and/or fluorescence in situ hybridization (FISH) results (as well as FLT3 results) on samples from blood or marrow that were obtained up to 3 weeks before signing consent for purposes of eligibility and stratification. In any case, results from FISH or karyotype should show if core-binding factor (CBF) abnormalities are present by time of randomization as the presence of CBF abnormalities is a required stratification factor
* Age \>= 18 and =\< 75 years

  * Because no dosing or adverse event (AE) data are currently available on the use of pembrolizumab (MK-3475) in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
* Eastern Cooperative Oncology Group (ECOG) performance status =\< -2
* The patient has to be eligible to receive intensive "7+3" induction chemotherapy as judged by the treating physician
* Prior use of hypomethylating agents (HMA), lenalidomide, erythropoiesis-stimulating agents (ESAs), and growth factors is allowed if used to treat prior MDS. AML must be previously untreated except as outlined below (hydroxyurea, or tretinoin \[ATRA\], or leukapheresis). Note: One dose of prophylactic intrathecal therapy is allowed during or before screening if a lumbar puncture is performed to rule out central nervous system (CNS) involvement
* Hydroxyurea/leukapheresis allowed for control of hyperleukocytosis but hydroxyurea must be discontinued day prior to start of chemotherapy
* Creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) \>= 60 mL/min for patient with creatinine levels \> 1.5 x institutional ULN (within 3 days prior to the first day of 7+3)

  * Creatinine clearance (CrCl) should be calculated per institutional standard
  * Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl
* Total bilirubin =\< 1.5 x ULN or direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 x ULN (within 3 days prior to the first day of 7+3)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN OR =\< 5 x ULN for patients with liver metastases (within 3 days prior to the first day of 7+3)
* International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 3 days prior to the first day of 7+3)
* Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (within 3 days prior to the first day of 7+3)
* Patients with a known history of being human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements:

  * They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective
  * Patients must have an undetectable HIV viral load
* Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. For patients with evidence of chronic hepatitis 

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• UC Irvine Health/Chao Family Comprehensive Cancer Center, Orange, California, United States
• Yale University, New Haven, Connecticut, United States
• Mayo Clinic in Florida, Jacksonville, Florida, United States
• Northwestern University, Chicago, Illinois, United States
• Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center, Lebanon, New Hampshire, United States
• Wake Forest University at Clemmons, Clemmons, North Carolina, United States
• Wake Forest Baptist Health - Wilkes Medical Center, Wilkesboro, North Carolina, United States
• Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States
• VCU Massey Comprehensive Cancer Center, Richmond, Virginia, United States

Frequently Asked Questions

Related Conditions

• Acute Myeloid Leukemia
• Myelodysplastic Syndrome
• Therapy-Related Acute Myeloid Leukemia
• Secondary Acute Myeloid Leukemia
• Hematologic Malignancies
• Leukemia
• Blood Cancers
• Oncology
• Immunotherapy
• Chemotherapy

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