Symptoms and General Pathology

All Conditions

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Blood and Lymph Conditions

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Rare Diseases

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Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

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Myelodysplastic Syndromes

Leukemia, Biphenotypic, Acute

Neoplasms by Histologic Type

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Bone Marrow Diseases

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Leukemia, Lymphoid

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Acute Leukemia of Ambiguous Lineage

Antineoplastic Agents

All Drugs and Chemicals

Venetoclax

Homoharringtonine

Enzyme Inhibitors

Patients receive omacetaxine SC BID on days 2-3 or 2-4, and venetoclax PO on days 1-7, 1-10 or 1-14. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Omacetaxine Mepesuccinate

Courtney DiNardo, MD

This phase Ib/II trial best dose, possible benefits and/or side effects of omacetaxine and venetoclax in treating patients with acute myeloid leukemia or myelodysplastic syndrome that has come back (recurrent) or does not respond to treatment (refractory) and have a genetic change RUNX1. Drugs used in chemotherapy, such as omacetaxine, 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 may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving omacetaxine and venetoclax may help to control the disease.

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability and recommended phase 2 dose (RP2D) of omacetaxine in combination with venetoclax for patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome harboring a RUNX1 mutation. (Phase 1b) II. To determine the efficacy of omacetaxine in combination with venetoclax for patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome harboring a RUNX1 mutation. (Phase II)

SECONDARY OBJECTIVES:

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

II. To evaluate occurrence of minimal residual disease (MRD) negative status by multiparameter flow cytometry and molecular evaluation.

EXPLORATORY OBJECTIVE:

I. To investigate global gene expression profiles, deoxyribonucleic acid (DNA) methylation profiles, BH3 profiling and other potential prognostic markers to explore predictors of antitumor activity and/or resistance to treatment.

OUTLINE: This is a phase I, dose de-escalation study followed by a phase II study.

Patients receive omacetaxine subcutaneously (SC) twice daily (BID) on days 2-3 or 2-4, and venetoclax orally (PO) on days 1-7, 1-10 or 1-14. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 30 days, then every 3 months for 3 years.

Omacetaxine and Venetoclax for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Harboring Mutant RUNX1

Phase Ib/II Study of Omacetaxine and Venetoclax for Patients With Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Harboring Mutant RUNX1

MRD negative status and exploratory biomarkers will be summarized graphically and with descriptive statistics. The association between molecular and cellular markers and overall response and/or resistance will be assessed through logistic regression analyses. Paired t-test or Wilcoxon signed rank test will be used to assess the marker change over time.

Safety data will be summarized using frequency and percentage, by category and severity.

Defined as the proportion of patients who had complete remission, complete remission with incomplete hematologic recovery, complete remission with incomplete count recovery, partial response or marrow clearance of blasts within 3 months of treatment initiation among adult patients with acute myeloid leukemia. Analyses will be performed for enrolled subjects, with laboratory response assessment occurring +/- 7 days from bone marrow evaluations. The depth of remission such as with exploratory analyses of minimal residual disease negativity by flow cytometry and/or concomitant molecular analysis will also be performed.

The Kaplan-Meier method will be used to estimate the probabilities. Log-rank tests will be used to compare among subgroups of patients in terms of EFS.

The Kaplan-Meier method will be used to estimate the probabilities. Log-rank tests will be used to compare among subgroups of patients in terms of OS.

The Kaplan-Meier method will be used to estimate the probabilities.

M.D. Anderson Cancer Center

Decitabine

Decitabine and cedazuridine drug combination

Antimetabolites

Patients receive decitabine and cedazuridine PO QD on days 1-10. Patients who achieve CR/CRi during consolidation/maintenance may receive decitabine and cedazuridine PO QD on days 1-5. Patients also receive venetoclax PO QD on days 1-28 of cycle 1 and days 1-21 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Decitabine and Cedazuridine

Abhishek Maiti

This phase II trial studies the effects of venetoxlax in combination with decitabine and cedazuridine in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). Chemotherapy drugs, such as venetoclax and decitabine, 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. Cedazuridine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving venetoxlax in combination with decitabine and cedazuridine may help to control acute myeloid leukemia.

PRIMARY OBJECTIVE:

I. To determine the overall response rate (complete remission \[CR\], complete remission with incomplete count recovery \[CRi\], MLFS and partial response \[PR\]) of 10-days decitabine and cedazuridine (oral decitabine) and venetoclax in patients with refractory/relapsed acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

I. To determine the duration of response, event-free survival (EFS), and overall survival (OS) of patients with refractory/relapsed AML treated with this combination.

II. To determine the number of patients who achieve a hematologic improvement (HI) in platelets, hemoglobin, or ANC and the number of patients who achieve \> 50% reduction in blasts on therapy with venetoclax/10-day oral decitabine.

III. To determine the safety of venetoclax in combination with 10-day oral decitabine in patients with refractory/ relapsed AML.

IV. To determine the number of patients who transition towards stem cell transplantation upon achieving response with the combination venetoclax/10-day oral decitabine regimen.

V. To determine the incidence of infectious complications per cycle with venetoclax in combination with 10-day oral decitabine.

EXPLORATORY OBJECTIVE:

I. To investigate global gene expression profiles, cytometry by time of flight (CyTOF), BH3 profiling and other potential prognostic markers to explore predictors of antitumor activity and/or resistance to treatment.

OUTLINE:

Patients receive decitabine and cedazuridine orally (PO) once daily (QD) on days 1-10. Patients who achieve CR/CRi during consolidation/maintenance may receive decitabine and cedazuridine PO QD on days 1-5. Patients also receive venetoclax PO QD on days 1-28 of cycle 1 and days 1-21 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Venetoclax in Combination With Decitabine and Cedazuridine for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

A Phase II Study of Venetoclax in Combination With 10-day Oral Decitabine in Relapsed/Refractory Acute Myeloid Leukemia

Defined as the proportion of patients who had complete remission (CR), complete remission with incomplete count recovery (CRi), partial response (PR) or MLFS. Will estimate the ORR for the combination treatment, along with the Bayesian 95% credible interval.

The overall incidence and severity of all adverse events using Common Toxicity Criteria version 5.0. Safety data will be summarized using frequency and percentage, by category and severity.

Will estimate for the combination treatment, along with the Bayesian 95% credible interval.

The Kaplan-Meier method will be used to estimate the survival probabilities of time-to-event variables such as EFS. Log-rank tests will be used to compare among subgroups of patients in terms of the time-to-event variables.

The Kaplan-Meier method will be used to estimate the survival probabilities of time-to-event variables such as OS. Log-rank tests will be used to compare among subgroups of patients in terms of the time-to-event variables.

Will examine the association between gene expression profiles and prognostic markers and overall response and/or resistance will be assessed through logistic regression analyses. Paired t-test or Wilcoxon signed rank test will be used to assess the marker change over time.

Sarcoma

Sarcoma, Myeloid

Acute Disease

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Myeloid Sarcoma

Anti-Infective Agents

Analgesics

Cytarabine

Mitoxantrone

Lenograstim

Cladribine

2-chloro-3'-deoxyadenosine

2'-deoxyadenosine

Cordycepin

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Adjuvants, Immunologic

Patients will receive induction with granulocyte colony-stimulating factor on days 0-5 (if peripheral white blood cell count is less than 20,000/uL), cladribine on days 1-5, cytarabine on 1-5, and mitoxantrone on days 1-3. Patients also receive venetoclax orally (PO) on days 1-14. Treatment repeats every 28-35 days for up to 2 induction cycles including mitoxantrone, and up to 4 consolidation cycles without mitoxantrone in the absence of disease progression or unacceptable toxicity.

Recombinant Granulocyte Colony-Stimulating Factor

Mary-Beth M. Percival

This phase I trial finds the best dose and side effects of venetoclax in combination with cladribine, cytarabine, granulocyte colony-stimulating factor, and mitoxantrone (CLAG-M) in treating patients with acute myeloid leukemia and high-grade myeloid neoplasms. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as cladribine, cytarabine, and mitoxantrone, 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 with CLAG-M may kill more cancer cells.

OUTLINE:

This is a dose-escalation study of venetoclax.

Patients will receive induction with granulocyte colony-stimulating factor on days 0-5 (if peripheral white blood cell count is less than 20,000/uL), cladribine on days 1-5, cytarabine on 1-5, and mitoxantrone on days 1-3. Patients also receive venetoclax orally (PO) on days 1-14. Treatment repeats every 28-35 days for up to 2 induction cycles including mitoxantrone, and up to 4 consolidation cycles without mitoxantrone in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 12 months.

Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms

A Phase 1 Single-Center Trial Combining Venetoclax With G-CSF, Cladribine, Cytarabine, and Mitoxantrone (CLAG-M) for Patients With AML and High-Grade Myeloid Neoplasms

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Omacetaxine and Venetoclax for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Harboring Mutant RUNX1	NCT04874194	Hematopoietic a... Recurrent Acute... Recurrent Acute... Recurrent Myelo... Refractory Acut... Refractory Acut... Refractory Myel...	Omacetaxine Mep... Venetoclax	18 Years -	M.D. Anderson Cancer Center
Omacetaxine and Venetoclax for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Harboring Mutant RUNX1	NCT04874194	Hematopoietic a... Recurrent Acute... Recurrent Acute... Recurrent Myelo... Refractory Acut... Refractory Acut... Refractory Myel...	Omacetaxine Mep... Venetoclax	18 Years -	M.D. Anderson Cancer Center
Venetoclax in Combination With Decitabine and Cedazuridine for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia	NCT04975919	Recurrent Acute... Recurrent Acute... Refractory Acut... Refractory Acut...	Decitabine and ... Venetoclax	18 Years -	M.D. Anderson Cancer Center
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms	NCT04797767	Acute Biphenoty... Acute Myeloid L... Mixed Phenotype... Myeloid Neoplas... Relapsed Acute ... Relapsed Acute ... Relapsed Mixed ... Relapsed Myeloi... Refractory Acut... Refractory Acut... Refractory Mixe... Refractory Myel... Recurrent Myelo...	Cladribine Cytarabine Mitoxantrone Recombinant Gra... Venetoclax	18 Years -	University of Washington

Spots Global Cancer Trial Database for refractory acute biphenotypic leukemia