Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Azacitidine

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

The treatment of relapsed and refractory AML patients.

The treatment of newly diagnosed AML patients (≥ 65 years) who are not candidates for intensive induction chemotherapy.

pembrolizumab

Azacitadine

Ivana Gojo, MD

This is a multicenter, nonrandomized, open-label phase 2 study (with a safety run-in phase) of azacitidine (AZA) 75 mg/m2 given IV or SQ on days 1-7 every 28 days in combination with pembrolizumab 200 mg given IV every 3 weeks (starting on day 8 of cycle 1). The dose/schedule of AZA selected for this study is FDA approved for patients with MDS/AML.

Acute myeloid leukemia (AML) remains a therapeutic challenge. Although 60-80% of newly diagnosed patients with AML respond to induction chemotherapy, the relapse rate remains high (40%-50%) even after allogeneic stem cell transplant (alloHSCT). Data suggests that epigenetic therapy with azacitidine combined with blockade of PD-1/PD-L1 pathway is a rational therapeutic approach both in newly diagnosed older patients and those with relapsed and refractory AML. Furthermore, recent data suggest that the addition of PD-1 blockade (nivolumab) to azacitidine in patients with AML who have previously failed hypomethylating agents may induce responses in up to 20% patients

We plan to examine two AML patient cohorts:

Cohort 1: relapsed/refractory AML. Cohort 2: newly diagnosed AML in older patients (≥65 years) not candidates for induction chemotherapy. Azacitidine and pembrolizumab have distinct mechanisms of action with no common overlapping toxicities; however, as azacitidine and pembrolizumab have not been tested previously in combination in AML patients, we plan to start enrollment with Cohort 1 (a safety run-in phase) and include only relapsed/refractory AML patients excluding those relapsing after allogeneic hematopoietic stem cell transplant (alloHSCT). The primary objective of the run in safety phase would be to determine the safe and tolerable dose/schedule of azacitidine and pembrolizumab in patients with AML. We will perform safety run in phase only in Cohort 1 as Cohort 2 patients would be expected to have a same or better tolerability given that they are not heavily pretreated

Study of Azacitidine in Combination With Pembrolizumab in R/R AML Patients and in Newly Diagnosed Older Patients

Phase 2 Study of Azacitidine in Combination With Pembrolizumab in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients and in Newly Diagnosed Older (≥65 Years) AML Patients

The primary objective is to determine the safe and tolerable dose for both the relapsed/refractory AML patients.

Response will be assessed using the International European LeukemiaNet Guidelines in AML63 and IWG Modified Response Criteria (2006) for CR and CRi. CR is bone marrow blasts \<5%; absence of circulating blasts; ANC \> or = 1, 000/mcL; platelet count \> or = 100,000/mcL. CRi is all CR criteria except for residual neutropenia (\<1,000/mcL) or thrombocytopenia (\<100,000/mcL).

Merck Sharp & Dohme LLC

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

The treatment of relapsed and refractory AML patients.

pembrolizumab: Intravenous pembrolizumab

Azacitadine: Intravenous or subcutaneous

Cohort 1: Relapsed/Refractory AML Patients

The treatment of newly diagnosed AML patients (≥ 65 years) who are not candidates for intensive induction chemotherapy.

pembrolizumab: Intravenous pembrolizumab

Azacitadine: Intravenous or subcutaneous

Cohort 2: Newly Diagnosed Older Patients Not Eligible for Intensive Chemo

The treatment of newly diagnosed AML patients (≥ 65 years) who are not candidates for intensive induction chemotherapy.

pembrolizumab: Intravenous pembrolizumab 200 mg every 3 weeks

Azacitadine: Intravenous or subcutaneous

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United States

Region of Enrollment

Dr. Ivana Gojo

New diagnosed older patients (greater than or equal to 65 years of age) who are not candidates for intensive induction chemotherapy.

This outcome was assessed only in Cohort 1.

Maximal Tolerable Dose of Pembrolizumab for Cohort 1

Number of Participants Who Had Complete Remission/Complete Remission With Incomplete Recovery

The treatment of relapsed/refractory AML patients receiving azacitidine and pembrolizumab.

Safety Run in Phase (Only Cohort 1)

New diagnosed older patients (greater than or equal to 65 years of age) who are not candidates for intensive induction chemotherapy receiving azacitidine and pembrolizumab.

Cohort 2 (Newly Diagnosed Patients)

Phase 1 (2 Years)

Phase (2 Years)

Anti-Infective Agents

Cytarabine

Venetoclax

Fludarabine

Fludarabine phosphate

Lenograstim

Vorinostat

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antiviral Agents

Histone Deacetylase Inhibitors

Enzyme Inhibitors

The subject receives 2 courses of therapy approximately 35 days each. Venetoclax: Days 1-14 Azacitidine and Vorinostat: Days 1-5 Filgrastim Days: 5 start and continue until post-nadir ANC \> 500 cells/mm3 Fludarabine and Cytarabine Days 6 - 10 IT Cytarabine Day 0 or 1, optional between day 35 and 42

Dose Level 0: Day 1 60 mg/m2 PO x1, Days 2-14 120 mg/m2/dose PO once daily (Max: 200 mg/day)

Dose level 1: Day 1 120 mg/m2 PO x1, Days 2-14 240 mg/m2/dose PO once daily (Max: 400 mg/day)

Dose level 2: Day 1 180 mg/m2 PO x1, Days 2-14 360 mg/m2/dose PO once daily (Max: 600 mg/day)

75 mg/m2/dose IV once daily over 15 minutes

1 year to 17.99 years old: 180 mg/m2/dose PO once daily

≥18 years old 200 mg PO BID. Doses should be separated by 12 hr (±4 hr)

2000 mg/m2/dose IV once daily over 3 hours

IT Cytarabine:

1. - 1.99 years old: 30 mg
2. - 2.99 years old: 50 mg

   * 3 years old: 70 mg

30 mg/m2/dose IV once daily over 30 minutes

5 microgram/kg/dose subcutaneous (or IV over 15-30 min) once daily

Filgrastim

Amberley Kemic, RN

Michael Burke, MD

Zachary T. Graff, MD

The investigator is testing the addition of venetoclax to 5-azacitidine and vorinostat followed by standard chemotherapy to enhance treatment response in AML patients.

The investigators are testing if the addition of venetoclax to epigenetic therapy will not only enhance the treatment response for patients with epigenetic lesions but improve the poor response we have observed in those patients without epigenetic lesions. The addition of venetoclax to 5-azacitidine and vorinostat followed by standard chemotherapy will be investigated. This regimen may be tolerable and increase LSC targeting resulting in deeper, more durable responses in children, adolescents, and young adults with relapsed or refractory AML

The study will enroll patients in two strata - a primary stratum of eligible patients without Down syndrome, and a secondary stratum of eligible patients with Down syndrome (DS-AML). Subjects will receive two 35 day cycles of therapy.

Venetoclax to Augment Epigenetic Modification and Chemotherapy

A Phase I Study of Venetoclax to Augment Epigenetic Modification and Chemotherapy in Pediatric and Young Adult Patients With Relapsed and Refractory Acute Myeloid Leukemia

The primary endpoint, for dose escalation of venetoclax, is the occurrence of a dose-limiting toxicity (DLT) observed during the first course of therapy.

Response rates as measured by morphologic response (CR)

Response rates as measured by morphologic response (PD)

Response rates as measured by morphologic response (SD)

Response rates as measured by morphologic response (CRi)

Response rates as measured by morphologic response (PR)

minimal residual disease (MRD) via multiparameter flow cytometry

Medical College of Wisconsin

Associate Professor, Department of Pediatrics, Division of Hematology/Oncology/BMT

Symptoms and General Pathology

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Precancerous Conditions

Central Nervous System Depressants

Other Dietary Supplements

Decitabine

Benzocaine

Tannic Acid

Pracinostat in combination with HMA treatment (either azacitidine or decitabine) used in initial single agent treatment for that patient

Histone deacetylase inhibitor (HDACi) Pracinostat is to be taken before HMA administration 3 times/week (e.g., Monday, Wednesday, and Friday) for 3 weeks, followed by 1 week of rest as a 28-day cycle. Pracinostat administration will be at the clinic on Day 1 of Cycles 1 and 2 and subject will self-administer at home on all other days

pracinostat

All patients will receive the dose and schedule of azacitadine to which they previously failed to respond. (e.g. 75 mg/m2 via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable; 7 days of each 28 day cycle, either Days 1-7, or Days 1-5, rest on Days 6-7, and azacitadine dosing on Days 8-9)

All patients will receive the dose and schedule of decitabine to which they previously failed to respond. Common 28 day treatment regimens include: 20 mg/m2 IV for either 5 or 10 days of each 28-day cycle, 10 mg/m2 given intravenously daily for first 10 days of each 28 day cycle, or 20 mg/m2 given subcutaneously daily for the first 5 days of each 28 day cycle.

The 6-week regimen utilizes a dose of 15 mg/m2 by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days repeated every 6 weeks.

Guillermo Garcia-Manero, MD

The purpose of this open label study is to determine whether combining pracinostat (study drug) with Vidaza (azacitidine) or Dacogen (decitabine) will improve clinical responses in Myelodysplastic Syndrome (MDS) patients who have failed an initial single agent hypomethylating agent (HMA), and to provide additional safety and efficacy data.

Phase 2 Study Adding Pracinostat to a Hypomethylating Agent (HMA) in Patients With MDS Who Failed to Respond to Single Agent HMA

A Phase II Simon Two-Stage Study of the Addition of Pracinostat to a Hypomethylating Agent (HMA) in Patients With Myelodysplastic Syndrome (MDS) Who Have Failed to Respond or Maintain a Response to the HMA Alone

Clinical Improvement Rate defined as the proportion of patients with CR, Marrow CR, PR, and HI.

Overall Response Rate (ORR), defined as the proportion of patients with CR, PR, Marrow CR, HI, SD, transfusion independence, and cytogenetic responses according to the IWG criteria

Complete response (CR) rate, defined as the proportion of patients with a confirmed CR (i.e., confirmed by a CBC at least 4 weeks after CR) according to the IWG criteria

Hematologic improvement (HI) rate, defined as the proportion of patients who demonstrate major hematologic improvement as defined by the IWG criteria. Only patients with pre-treatment abnormal values will be considered for this endpoint at 8 weeks.

Duration of Response (for patients who have achieved CR, PR, or HI), defined as the time from the initial determination of response to the time of disease progression or death on study, whichever occurs first. For patients who are alive and have not experienced disease progression on study (prior to receiving subsequent/new treatment or stem cell transplant), duration of response will be censored at the day of the last adequate disease assessment.

Progression-Free survival (PFS), defined as the time from first day of study drug administration (Day 1) to either disease progression or death. Patients who have not progressed or are alive will be censored at the date of last adequate disease assessment

Event Free Survival (EFS) defined as the time from first day of study drug administration (Day 1) to failure or death from any cause according to the IWG response criteria. Patients who have not progressed, are alive or died without progression will be censored at the date of last adequate disease assessment

Overall Survival (OS), defined as the time from the first day of study drug administration (Day 1) to death on study. Patients who are alive will be censored at the date last known alive.

Assess the adverse event (AE) profile of pracinostat combined with either azacitidine or decitabine by clinical review of safety events by grade, relationship and event outcomes.

Marrow CR rate, defined as bone marrow \<5% myeloblasts and decrease by \> 50% over pretreatment according to IWG criteria.

Transfusion independence, defined as during the treatment period the patient had no RBC transfusions during any 56 consecutive days or more.

Stable disease rate defined as failure to achieve at least a PR, but no evidence of progression for \> 8 weeks according to IWG criteria.

Cytogenetic response rate, defined as complete disappearance of the chromosomal abnormality without appearance of new abnormalities, or partial response of at least 50% reduction of the chromosomal abnormality according to IWG criteria.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Azacitidine in Combination With Pembrolizumab in R/R AML Patients and in Newly Diagnosed Older Patients	NCT02845297	Acute Myeloid L...	pembrolizumab Azacitadine	18 Years - 65 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Venetoclax to Augment Epigenetic Modification and Chemotherapy	NCT05317403	Acute Myeloid L... Acute Myeloid L...	Venetoclax Azacitadine Vorinostat Cytarabine Fludarabine Filgrastim	1 Year - 25 Years	Medical College of Wisconsin
Phase 2 Study Adding Pracinostat to a Hypomethylating Agent (HMA) in Patients With MDS Who Failed to Respond to Single Agent HMA	NCT01993641	Myelodysplastic... MDS	pracinostat Azacitidine Decitabine	18 Years -	Helsinn Healthcare SA

Spots Global Cancer Trial Database for azacitadine

Every month we try and update this database with for azacitadine cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for azacitadine

Every month we try and update this database with for azacitadine cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for azacitadine cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.