BLockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia 2 (BLAST MRD AML-2): A Randomized Phase 2 Study of the Venetoclax, Azacitadine, and Pembrolizumab (VAP) Versus Venetoclax and Azacitadine as First Line Therapy in Older Patients With Acute Myeloid Leukemia (AML) Who Are Ineligible or Who Refuse Intensive Chemotherapy

Plain English Summary

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 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 (an immunotherapy) to standard treatment (azacitidine and venetoclax) helps eliminate leukemia cells that are too small to detect. It is for older adults newly diagnosed with Acute Myeloid Leukemia (AML) who are not eligible for or choose not to have intensive chemotherapy. Participants will receive either the standard treatment alone or the standard treatment plus pembrolizumab, and will undergo regular blood draws and bone marrow tests. Alternative treatments include standard chemotherapy, other targeted therapies, or stem cell transplant, depending on the patient's specific situation and doctor's recommendation. The trial aims to enroll 60 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 60 years or older with newly diagnosed AML. Patients who are considered unfit for intensive chemotherapy or who refuse it. Must not have had prior treatment for AML, except for certain medications for related conditions like MDS. Patients with certain genetic abnormalities in their leukemia (core-binding factor abnormalities) cannot participate. 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 main goal is to see if more patients achieve a complete remission where no leukemia cells can be detected (minimal residual disease negative), meaning the treatment is working very well. The specific primary outcome measures are: 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)). 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 older AML patients by investigating if adding immunotherapy can achieve deeper remission and prevent the leukemia from returning, addressing a need for more eff 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 targets a significant unmet need in AML treatment for older, unfit patients, potentially expanding the use of immunotherapy in this setting and offering a competitive advantage if successfu 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 risks and benefits of each treatment arm and how this trial fits with your overall health. Participation involves regular clinic visits for medication, blood tests, and bone marrow biopsies to monitor your response and any side effects. The study treatment is given in cycles, and you will be monitored closely throughout the trial. The trial is being conducted at 20 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: 60 participants

Interventions

• DRUG: Azacitidine — Given IV or SC
• PROCEDURE: Biopsy Procedure — Undergo biopsy
• PROCEDURE: Biospecimen Collection — Undergo blood specimen collection
• PROCEDURE: Bone Marrow Aspiration — Undergo bone marrow aspiration
• PROCEDURE: Bone Marrow Biopsy — Undergo bone marrow biopsy

Primary Outcomes

• 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

• Proportion of Patients Who Develop Severe Toxicity (Up to cycle 2 (each cycle is 28 days))

Full Eligibility Criteria

Inclusion Criteria:

* 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
* Intermediate-risk or poor risk AML as well as favorable risk by National Comprehensive Cancer Network (NCCN)/European LeukemiaNet (ELN) with the exception of "good-risk" cytogenic profile (i.e., for eligibility patient should lack the presence of t(8;21), (inv\[16\] or t\[16;16\]), or t(15;17) by full cytogenetics or FISH). Clarification: We allow use of karyotype and/or 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. Adverse karyotype can be determined based on FISH results (e.g., loss of chromosome 7 or 5 or 3 or more abnormalities) based on the specific probes used in the FISH. If results of full metaphase karyotype are not available and the available FISH results do not suggest an adverse karyotype, and there is a need to initiate therapy before those full results are available, then the patient can be stratified into the unknown/intermediate NCCN cytogenetic group for randomization purposes. In any case, results from FISH or karyotype should show that core-binding factor (CBF) abnormalities are NOT present by at time of randomization as the presence of CBF abnormalities is an exclusion factor
* 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 tra

Trial Locations

• Smilow Cancer Hospital Care Center at Greenwich, Greenwich, Connecticut, United States
• Smilow Cancer Hospital Care Center at Saint Francis, Hartford, Connecticut, United States
• Yale University, New Haven, Connecticut, United States
• MedStar Georgetown University Hospital, Washington D.C., District of Columbia, United States
• Northwestern University, Chicago, Illinois, United States
• HaysMed, Hays, Kansas, United States
• University of Kansas Cancer Center, Kansas City, Kansas, United States
• Lawrence Memorial Hospital, Lawrence, Kansas, United States
• The University of Kansas Cancer Center - Olathe, Olathe, Kansas, United States
• University of Kansas Cancer Center-Overland Park, Overland Park, Kansas, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Acute Myeloid Leukemia (AML)
• Myelodysplastic Syndromes (MDS)
• Myeloproliferative Neoplasms (MPN)
• Aplastic Anemia
• Hematologic Malignancies
• Leukemia
• Blood Cancers
• Oncology
• Immunotherapy
• Targeted Therapy

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