BLAST MRD AML-2: BLockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia 2- A Randomized Phase 2 Study of Anti-PD-1 Pembrolizumab in Combination With Azacitidine and Venetoclax as Frontline Therapy in Unfit Patients With Acute Myeloid Leukemia

NCT04284787 | Active Not Recruiting Phase 2 Results FDA Drug

• 4 other identifiers: NCI-2020-01016200003164110334UM1CA186689
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 29

Brief Summary

This phase II trial studies how well azacitidine and venetoclax with or without pembrolizumab work in treating older patients with newly diagnosed acute myeloid leukemia. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. 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 azacitidine and venetoclax with pembrolizumab may increase the rate of deeper/better responses and reduce the chance of the leukemia coming back in patients with newly diagnosed acute myeloid leukemia compared to conventional therapy of azacitidine and venetoclax alone.

Conditions

Acute Myeloid Leukemia; Acute Myeloid Leukemia Post Cytotoxic Therapy; Secondary Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Minimal Residual Disease Negative Complete Remission (MRD-CR) or MRD-complete Remission With Incomplete Count Recovery (Cri) With Azacitidine (AZA) + Venetoclax (VEN) With MK-3475 (Pembrolizumab)

  Up to 6 cycles (each cycle is 28 days)

Secondary Outcomes (1)

• Proportion of Patients Who Develop Severe Toxicity

  Up to cycle 2 (each cycle is 28 days)

Other Outcomes (8)

• Biomarkers or Serial Measurements of Biomarkers Associated With Response Outcomes

  Baseline up to 3 years

• Biomarkers or Serial Measurements of Biomarkers Associated With Survival Outcomes

  Baseline up to 3 years

• Biomarkers Effects Between Treatment Arms

  Up to 3 years

Study Arms (2)

Arm I (AZA, VEN)

ACTIVE COMPARATOR

See Detailed Description

Drug: Azacitidine; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Drug: Venetoclax

Arm II (AZA, VEN, pembrolizumab)

EXPERIMENTAL

See Detailed Description

Drug: Azacitidine; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Biological: Pembrolizumab; Drug: Venetoclax

Interventions

Azacitidine DRUG

Given IV or SC

Also known as: 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Arm I (AZA, VEN); Arm II (AZA, VEN, pembrolizumab)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Arm I (AZA, VEN); Arm II (AZA, VEN, pembrolizumab)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Arm I (AZA, VEN); Arm II (AZA, VEN, pembrolizumab)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Arm I (AZA, VEN); Arm II (AZA, VEN, pembrolizumab)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Arm I (AZA, VEN); Arm II (AZA, VEN, pembrolizumab)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA scan

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Arm I (AZA, VEN); Arm II (AZA, VEN, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, Pembrolizumab Biosimilar RPH-075, Pembrolizumab Biosimilar SB27, QL2107, RPH 075, RPH-075, RPH075, SB 27, SB-27, SB27, SCH 900475, SCH-900475, SCH900475

Arm II (AZA, VEN, pembrolizumab)

Biospecimen Collection PROCEDURE

Undergo blood specimen collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (AZA, VEN); Arm II (AZA, VEN, pembrolizumab)

Venetoclax DRUG

Given PO

Also known as: ABT 199, ABT-0199, ABT-199, ABT199, GDC 0199, GDC-0199, GDC0199, RG7601, Venclexta, Venclyxto

Arm I (AZA, VEN); Arm II (AZA, VEN, pembrolizumab)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed and pathologically-confirmed, previously untreated AML as defined by World Health Organization (WHO) criteria. 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 arising from prior myelodysplastic syndrome (MDS), as long as they have not received more than full cycle of hypomethylating agent therapy for MDS, and therapy related (t)-AML are also allowed. AML arising from antecedent hematologic disorders defined as prior MDS, myeloproliferative neoplasm (MPN), or aplastic anemia are 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 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 exclude presence of core-binding factor (CBF) abnormalities by time of randomization
• Age \>= 60 years
• Patients who are ineligible for intensive chemotherapy according to treating physician's assessment or who refuse intensive chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
• Prior use of lenalidomide, erythropoiesis-stimulating agents (ESAs), and growth factors is allowed if used to treat prior MDS. AML must be previously untreated except for hydroxyurea, or all-trans retinoic acid (ATRA) for suspicion of APL but both should be discontinued prior to initiation of study therapy. Hypomethylating agents are not allowed to have been used for AML therapy. If hypomethylating agent therapy was used for prior MDS or MPN therapy then it should not have exceeded one full cycle. 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 or leukopheresis are allowed for management of hyperleukocytosis, as well as ATRA, before initiation of study therapy. White blood cell (WBC) count must be \< 25 x 10\^9/L to start on study therapy per venetoclax label. Hydroxyurea and ATRA may be administered up to one day prior to start of study treatment
• 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
• 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
• 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
• Patients who are 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 B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

You may not qualify if:

• Patients with CBF-AML and acute promyelocytic leukemia (APL)
• Received a prior anti-cancer monoclonal antibodies (mAb) within 4 weeks prior to study registration or have not recovered (recovery defined as baseline or =\< grade 1) from adverse events (AEs) due to agents administered more than 4 weeks earlier
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Patients who have had chemotherapy, targeted small molecule therapy (aside from imatinib, dasatinib, or nilotinib, hydroxyurea, or ATRA), or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
• Left ventricular ejection fraction \< 50% as determined by either echocardiogram or MUGA
• Patients who have not recovered from AEs due to prior anti-cancer therapy (i.e., 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
• Patients currently participating and receiving study therapy or have participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment are ineligible
• History of hypersensitivity to pembrolizumab (MK-3475) or any of its excipients, or other agents used in this study
• Current use of systemic corticosteroids or immunosuppressive agents
• EXCEPTION: Low doses of steroids (\< 10 mg of prednisone or equivalent dose of other steroid), used for treatment of non-hematologic medical condition (e.g., chronic adrenal insufficiency) inhaled corticosteroids, or topical steroids are permitted
• 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)
• Patient with known active CNS disease and/or carcinomatous meningitis before study enrollment. Assessment of the cerebrospinal fluid (CSF) is not required to enroll in the study unless there is clinical suspicion for CNS involvement. However, if CSF assessment is performed for any reason, there should be no evidence of active leukemia in the CSF as per investigator judgement. Up to one dose of prophylactic intrathecal chemotherapy is allowed prior to study enrollment. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of protocol treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to protocol treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Patients who received prior allogenic transplant

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (29)

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut, 06830, United States

Location

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

HaysMed

Hays, Kansas, 67601, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Lawrence Memorial Hospital

Lawrence, Kansas, 66044, United States

Location

The University of Kansas Cancer Center - Olathe

Olathe, Kansas, 66061, United States

Location

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, 66210, United States

Location

Mercy Hospital Pittsburg

Pittsburg, Kansas, 66762, United States

Location

Salina Regional Health Center

Salina, Kansas, 67401, United States

Location

University of Kansas Health System Saint Francis Campus

Topeka, Kansas, 66606, United States

Location

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States

Location

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

Location

University Health Truman Medical Center

Kansas City, Missouri, 64108, United States

Location

University of Kansas Cancer Center - North

Kansas City, Missouri, 64154, United States

Location

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064, United States

Location

University of Kansas Cancer Center at North Kansas City Hospital

North Kansas City, Missouri, 64116, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

Location

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136, United States

Location

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Wake Forest University at Clemmons

Clemmons, North Carolina, 27012, United States

Location

Wake Forest Baptist Health - Wilkes Medical Center

Wilkesboro, North Carolina, 28659, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; Biopsy; Specimen Handling; pembrolizumab; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Amer Zeidan, MBBS Professor of Internal Medicine (Hematology)
• Organization: Yale School of Medicine

amer.zeidan@yale.edu

(203) 200-4363

Study Officials

• Amer M Zeidan

  Yale University Cancer Center LAO

  PRINCIPAL INVESTIGATOR

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: February 25, 2020
• First Posted: February 26, 2020
• Study Start: February 16, 2021
• Primary Completion: June 5, 2023
• Study Completion (Estimated): January 30, 2027
• Last Updated: April 13, 2026
• Results First Posted: March 13, 2025

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (29)