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
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
4 other identifiers
interventional
49
1 country
10
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Feb 2021
Longer than P75 for phase_2
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 30, 2019
CompletedFirst Posted
Study publicly available on registry
January 2, 2020
CompletedStudy Start
First participant enrolled
February 17, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 27, 2024
CompletedResults Posted
Study results publicly available
March 4, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
January 30, 2027
ExpectedApril 13, 2026
December 1, 2025
3.8 years
December 30, 2019
November 26, 2025
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Rate of Minimal Residual Disease (MRD) Negative - Complete Response (CR)/Complete Remission With Incomplete Recovery (CRi)
MRD will be assessed by multicolor flow cytometry at a central laboratory as an integral biomarker.
78 days (mean)
Rate of MRD-negative CR
33 days (mean)
Secondary Outcomes (7)
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)
- +2 more secondary outcomes
Other Outcomes (10)
Rates of Complete Remission With Partial Recovery Count and Hematologic Improvement to Red Blood Cells and Platelets
Up to end of maintenance
MRD Assessment
Up to end of consolidation
MRD Detection
Up to end of consolidation
- +7 more other outcomes
Study Arms (2)
Arm I (cytarabine, idarubicin,daunorubicin,pembrolizumab,HSCT)
EXPERIMENTALSee Detailed Description.
Arm II (cytarabine, idarubicin, daunorubicin, HSCT)
ACTIVE COMPARATORSee Detailed Description.
Interventions
Undergo collection of blood
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Given IV
Undergo a skin punch biopsy
Undergo CT
Given via continuous IV infusion
Given IV
Undergo ECHO
Undergo HSCT
Given IV
Undergo MUGA
Eligibility Criteria
You may qualify if:
- 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:
- +8 more criteria
You may not qualify if:
- Patients with a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Prior treatment with the following are not allowed:
- Patients who have received anthracyclines for treatment of a prior, unrelated, curatively-treated malignancy which would limit their ability to receive 7 + 3 chemotherapy treatment on study
- Anti-PD-1, anti-PD-L1, or anti-PD-L2, for a prior, unrelated, curatively-treated malignancy, within last 3 months of enrollment in the study
- Anti-cancer monoclonal antibody (mAb) within 4 weeks, for a prior, unrelated, curatively-treated malignancy, prior to study registration or have not recovered (recovery defined as baseline or =\< grade 1) from AEs due to agents administered more than 4 weeks earlier
- Experimental treatment within 4 weeks prior to study registration
- Patients who have had chemotherapy (except hydroxyurea and all trans retinoic acid \[ATRA\] which are allowed but have to be stopped the day before induction therapy starts), targeted small molecule therapy (aside from imatinib, dasatinib, or nilotinib), or curative-intent radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C), for a prior curatively treated malignancy, prior to entering the study
- Patients who have received prior anthracyclines not to exceed 150 mg/m\^2 of daunorubicin or equivalent for treatment of a prior, unrelated, curatively-treated malignancy which would limit their ability to receive 7 + 3 chemotherapy treatment on study
- Patients with a cardiac ejection fraction less than 50% as determined by echocardiogram or radionuclide ventriculogram scan (MUGA) scan
- Other active primary malignancy (other than non-melanomatous skin cancer or carcinoma in situ of the cervix) requiring treatment or limiting expected survival to =\< 2 years
- NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy for their cancer)
- Patients who have FLT3-mutated AML
- FLT3-ITD or TKD mutations are defined as a mutation with a ratio of mutant to wild-type allele \>= 0.05 or variant allele fraction of \>= 5% by polymerase chain reaction (PCR) or next generation sequencing from either bone marrow or peripheral blood
- Note 1: FLT3, karyotype, or FISH results from bone marrow or peripheral blood that were performed up to 3 weeks before initiation of trial therapy are acceptable for eligibility determination or therapy stratification as long as they are performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory. Note 2: Patients are stratified based on age (younger than 65 versus \[vs\] 65 and older), presence of core-binding abnormalities by FISH or karyotype (yes/no), and by having t- AML or AML arising from prior/antecedent MDS (yes/no)
- Patients who have not recovered from AEs due to prior anti-cancer therapy (i.e., have not returned to baseline or have residual toxicities \> grade 1) with the exception of =\< grade 2 neuropathy and alopecia
- NOTE: Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\< 2 weeks of radiotherapy) to non-CNS disease
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Yale University
New Haven, Connecticut, 06520, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Northwestern University
Chicago, Illinois, 60611, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Wake Forest University at Clemmons
Clemmons, North Carolina, 27012, United States
Wake Forest Baptist Health - Wilkes Medical Center
Wilkesboro, North Carolina, 28659, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Amer Zeidan, MBBS
- Organization
- Yale University - MEDCCC Hematology
Study Officials
- PRINCIPAL INVESTIGATOR
Amer M Zeidan
Yale University Cancer Center LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 30, 2019
First Posted
January 2, 2020
Study Start
February 17, 2021
Primary Completion
November 27, 2024
Study Completion (Estimated)
January 30, 2027
Last Updated
April 13, 2026
Results First Posted
March 4, 2026
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.