Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, T-Cell

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Biphenotypic, Acute

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Acute Leukemia of Ambiguous Lineage

Leukemia, T-cell, Chronic

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Venetoclax

Azacitidine

Antimetabolites

Enzyme Inhibitors

Patients receiving venetoclax and azacitidine for maintenance after allogeneic stem cell transplantation, receive azacitidine SC on days 1-5 and venetoclax PO QD on days 1-7. Patients receiving venetoclax and azacitidine for minimal residual disease after allogeneic stem cell transplant, receive azacitidine SC on days 1-7 and venetoclax PO QD on days 1-14. Treatment repeats every 4-8 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Betul Oran

This phase II trial studies how well venetoclax and azacitidine work for the treatment of acute myeloid leukemia after stem cell transplantation. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as azacitidine, 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. Giving venetoclax and azacitidine after a stem cell transplant may help control high risk leukemia and prevent it from coming back after the transplant.

PRIMARY OBJECTIVE:

1. To determine relapse-free survival after the use of venetoclax in combination with azacitidine given as maintenance therapy or for eradication of minimal residual disease in patients with high risk acute myeloid leukemia (AML) after hematopoietic stem cell transplantation (HSCT).

SECONDARY OBJECTIVES:

1. To determine the safety and toxicity of venetoclax in combination with azacitidine (type, frequency, severity of adverse events \[AEs\] and relationship of AEs to venetoclax)
2. To determine response duration, overall survival.
3. To determine Incidence of acute and chronic graft versus host disease (GVHD)
4. To perform matched pairs analysis to obtain bias corrected treatment comparisons of Venetoclax + Vidaza (V+V) to standard therapy in AML patients with no evidence of disease (AML D-) subgroup.

EXPLORATORY OBJECTIVE:

1. To investigate possible relationships between baseline protein and gene expression signatures/mutation profile and BH3 profiling in predicting relapse-free survival time to the combination. This exploratory analysis will be done for the data from the entire study, accounting for the noted biological variables covariates, as well as disease status and whether or not the patient had AML, by fitting a Bayesian time-to-event regression model with RFS the outcome variable.

OUTLINE:

Patients receiving venetoclax and azacitidine for maintenance after allogeneic stem cell transplantation, receive azacitidine subcutaneously (SC) on days 1-5 and venetoclax orally (PO) once daily (QD) on days 1-7. Patients receiving venetoclax and azacitidine for minimal residual disease after allogeneic stem cell transplant, receive azacitidine SC on days 1-7 and venetoclax PO QD on days 1-14. Treatment repeats every 4-8 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Venetoclax and Azacitidine for the Treatment of Acute Myeloid Leukemia in the Post-Transplant Setting

A Phase II Study of Venetoclax in Combination With Azacitidine in the Post-Transplant Setting for AML, T Cell Leukemia, and Mixed Phenotype Acute Leukemia

Summary statistics for RFS time will be computed for all patients and within each (disease status, disease type) subgroup. RFS time distributions will be estimated within each subgroup using the method of Kaplan and Meier.

Summary statistics for OS time will be computed for all patients and within each (disease status, disease type) subgroup. OS time distributions will be estimated within each subgroup using the method of Kaplan and Meier.

Will be summarized, and relevant parameters will be estimated under appropriate Bayesian models.

Defined as death from any cause, within 90 days from the start of V+V treatment that is not preceded by disease recurrence. Will be summarized, and relevant parameters will be estimated under appropriate Bayesian models.

M.D. Anderson Cancer Center

Symptoms and General Pathology

Syndrome

Recurrence

Preleukemia

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Disease Attributes

Bone Marrow Diseases

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Chronic Disease

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Anti-Obesity Agents

Vasoconstrictor Agents

Respiratory System Agents

Phenylpropanolamine

Guaifenesin

Chlorpheniramine, phenylpropanolamine drug combination

Patients receive azacitidine SC or IV over 30 minutes on days 1-7 and enasidenib mesylate PO QD beginning on day 1. Cycles repeat every 4-6 weeks in the absence of disease progression or unacceptable toxicity.

Enasidenib Mesylate

Courtney DiNardo

This phase II trial studies how well enasidenib and azacitidine work in treating patients with IDH2 gene mutation and acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). Enasidenib and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the clinical activity of enasidenib mesylate (AG221, IDHIFA) in combination with azacitidine (AZA) for patients with relapsed/refractory acute myeloid leukemia is measured by overall response rate (ORR).

SECONDARY OBJECTIVES:

I. To determine duration of response, event-free survival (EFS), and overall survival (OS).

II. To determine the safety of enasidenib in combination with azacitidine in patients with relapsed/refractory acute myeloid leukemia (AML).

EXPLORATORY OBJECTIVES:

I. To evaluate occurrence of minimal residual disease (MRD) negative status by IDH2 mutation analysis and flow cytometry.

II. To investigate possible relationships between baseline protein and gene expression signatures and mutation profile and clinical response to the combination.

III. To evaluate the incidence and characteristics of IDH-inhibitor related differentiation syndrome (IDH-DS) with combination therapy.

OUTLINE:

Patients receive azacitidine subcutaneously (SC) or intravenously (IV) over 30 minutes on days 1-7 and enasidenib mesylate orally (PO) once daily (QD) beginning on day 1. Cycles repeat every 4-6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 5 years.

Enasidenib and Azacitidine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia and IDH2 Gene Mutation

Phase II Study of the Targeted Mutant IDH2 Inhibitor Enasidenib in Combination With Azacitidine for Relapsed/Refractory AML

MRD negative status and exploratory biomarkers will be summarized graphically and with descriptive statistics.

Association between molecular and cellular markers and overall response and/or resistance assessed through logistic regression analyses.

Paired t-test or Wilcoxon signed rank test will be used to assess the marker change over time.

The study will estimate the ORR for the combination treatment, along with the Bayesian 95% credible interval. ORR will be defined as the proportion of patients who had CR (complete remission), CRh (complete remission with incomplete hematologic recovery), CRi (complete remission with incomplete count recovery), PR (partial response), and/or marrow clearance of blasts (MLFS).

Kaplan-Meier method will be used to estimate the probabilities of event-free survival.

Kaplan-Meier method will be used to estimate the probabilities of overall survival.

Log-rank tests will be used to compare among subgroups of patients in terms of DFS or OS.

National Cancer Institute (NCI)

Neoplasm Metastasis

Precancerous Conditions

Antibodies

Antibodies, Monoclonal

Nivolumab

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive azacitidine IV over 1 hour or SC on days 1-7 or days 1-4 and 7-9. Patients also receive nivolumab IV over 60 minutes on days 1 and 14 (courses 1-4) or on day 1 (course 5 and all subsequent courses). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive azacitidine and nivolumab as Arm I. Patients also receive ipilimumab IV over 90 minutes on day 1 and then every 6 or 12 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Naval Daver

This phase II trial studies the side effects and best dose of nivolumab and azacitidine with or without ipilimumab when given together and to see how well they work in treating patients with acute myeloid leukemia that has not responded to previous treatment or has returned after a period of improvement or is newly diagnosed. Monoclonal antibodies, such as nivolumab and ipilimumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as azacitidine, 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. Giving nivolumab, azacitidine and ipilimumab may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of nivolumab in combination with azacitidine (5-azacytidine) in patients with refractory/relapsed acute myeloid leukemia (AML). (Lead-in phase) II. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of nivolumab with ipilimumab in combination with 5-azacytidine in patients with refractory/relapsed acute myeloid leukemia (AML). (Lead-in phase) III. To determine the overall response rate (ORR) of nivolumab in combination with 5-azacytidine in patients with refractory/ relapsed AML. (Phase II) IV. To determine the overall response rate (ORR) of nivolumab in combination with 5-azacytidine in older patients (\> 65 years) with newly diagnosed AML. (Phase II) V. To determine the overall response rate (ORR) of nivolumab with ipilimumab in combination with 5-azacytidine in patients with refractory/relapsed AML. (Phase II) VI. To determine the overall response rate (ORR) of nivolumab with ipilimumab in combination with 5- azacytidine in older patients (65 years) with newly diagnosed AML. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the number of patients who achieve a \> 50% reduction in blasts on therapy with either vidaza+nivolumab or vidaza+nivolumab+ipilimumab.

II. To determine the duration of response, disease-free survival (DFS), and overall survival (OS) of patients with refractory/relapsed AML treated with either vidaza+nivolumab or vidaza+nivolumab+ipilimumab.

III. To determine the duration of response, disease-free survival (DFS), and overall survival (OS) in older patients with newly diagnosed AML treated with this combination with either vidaza+nivolumab or vidaza+nivolumab+ipilimumab.

TERTIARY OBJECTIVES:

I. To study immunological and molecular changes in the peripheral blood and bone marrow in response to nivolumab and 5-azacytidine therapy or nivolumab with ipilimumab and 5-azacytidine therapy.

II. To determine induction of hypomethylation and deoxyribonucleic acid (DNA) damage during therapy with this combination and its correlation with response.

OUTLINE: This is a lead-in phase, dose-escalation study followed by a phase II study. Patients are assigned to 1 of 2 arms.

ARM I: Patients receive azacitidine intravenously (IV) over 1 hour or subcutaneously (SC) on days 1-7 or days 1-4 and 7-9. Patients also receive nivolumab IV over 60 minutes on days 1 and 14 (courses 1-4) or on day 1 (course 5 and all subsequent courses). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive azacitidine and nivolumab as Arm I. Patients also receive ipilimumab IV over 90 minutes on day 1 and then every 6 or 12 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 5 years.

Nivolumab and Azacitidine With or Without Ipilimumab in Treating Patients With Refractory/Relapsed or Newly Diagnosed Acute Myeloid Leukemia

An Open-Label Phase II Study of Nivolumab (BMS-936558) in Combination With 5-Azacytidine (Vidaza) or Nivolumab With Ipilimumab in Combination With 5-Azacytidine for the Treatment of Patients With Refractory/ Relapsed Acute Myeloid Leukemia and Newly Diagnosed Older AML (&gt; 65 Years) Patients

Determined using paired t-tests. Descriptive statistics including plots, mean, median and standard deviations will be used to summarize data. For continuous outcomes, t-tests and analysis of variance will be used to compare outcome measures across patient characteristics. Dunnett's and Tukey's test that properly adjust for multiplicity in multiple test will be implemented. Pair-wise comparison's will be performed using pre- and post-therapy samples from each patient. The chi-square test or Fisher's exact test will be used to test the association between categorical variables such as disease state and performance status. Both univariate and multivariate logistic regressions will be performed to model prognostic factors.

Correlation analysis (such as logistic regression analysis) will be conducted to determine the relationship between induction of hypomethylation/deoxyribonucleic acid damage and clinical response.

The maximum tolerated dose is defined as the highest dose level with \< 2 out of 6 patients experiencing a dose limiting toxicity during the first 28 days of treatment.

Will be presented along with 95% confidence interval. The association between overall response rate and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test as appropriate.

Toxicity type, severity and attribution will be summarized for each patient using frequency tables.

Will be estimated using the method of Kaplan and Meier.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Venetoclax and Azacitidine for the Treatment of Acute Myeloid Leukemia in the Post-Transplant Setting	NCT04128501	Acute Bilineal ... Acute Biphenoty... Acute Myeloid L... Mixed Phenotype... T Acute Lymphob... Therapy-Related...	Azacitidine Venetoclax	18 Years - 75 Years	M.D. Anderson Cancer Center
Enasidenib and Azacitidine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia and IDH2 Gene Mutation	NCT03683433	Acute Bilineal ... Acute Biphenoty... Chronic Myelomo... IDH2 Gene Mutat... Myelodysplastic... Recurrent Acute... Refractory Acut...	Azacitidine Enasidenib Mesy...	18 Years -	M.D. Anderson Cancer Center
Venetoclax and Azacitidine for the Treatment of Acute Myeloid Leukemia in the Post-Transplant Setting	NCT04128501	Acute Bilineal ... Acute Biphenoty... Acute Myeloid L... Mixed Phenotype... T Acute Lymphob... Therapy-Related...	Azacitidine Venetoclax	18 Years - 75 Years	M.D. Anderson Cancer Center
Enasidenib and Azacitidine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia and IDH2 Gene Mutation	NCT03683433	Acute Bilineal ... Acute Biphenoty... Chronic Myelomo... IDH2 Gene Mutat... Myelodysplastic... Recurrent Acute... Refractory Acut...	Azacitidine Enasidenib Mesy...	18 Years -	M.D. Anderson Cancer Center
Nivolumab and Azacitidine With or Without Ipilimumab in Treating Patients With Refractory/Relapsed or Newly Diagnosed Acute Myeloid Leukemia	NCT02397720	Acute Bilineal ... Acute Biphenoty... Acute Myeloid L... Chronic Myelomo... Myelodysplastic... Recurrent Acute... Refractory Acut... Secondary Acute... Therapy-Related...	Azacitidine Ipilimumab Laboratory Biom... Nivolumab	18 Years -	M.D. Anderson Cancer Center
Venetoclax and Azacitidine for the Treatment of Acute Myeloid Leukemia in the Post-Transplant Setting	NCT04128501	Acute Bilineal ... Acute Biphenoty... Acute Myeloid L... Mixed Phenotype... T Acute Lymphob... Therapy-Related...	Azacitidine Venetoclax	18 Years - 75 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for acute bilineal leukemia