Entinostat and Clofarabine in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Poor-Risk Acute Lymphoblastic Leukemia or Bilineage/Biphenotypic Leukemia

Recurrent Adult Acute Lymphoblastic Leukemia Clinical Trial

Official title: A Phase I Study of the Histone Deacetylase Inhibitor Entinostat (SNDX-275, NSC 706995) Plus Clofarabine for Philadelphia Chromosome-Negative, Poor Risk Acute Lymphoblastic Leukemia or Bilineage/Biphenotypic Leukemia in Newly Diagnosed Older Adults or in Adults With Relapsed and Refractory Disease

Status Completed

Clinical Trial Summary

This phase I trial studies the side effects and best dose of entinostat when given together with clofarabine in treating patients with newly diagnosed, relapsed, or refractory poor-risk acute lymphoblastic leukemia or bilineage/biphenotypic leukemia. Entinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving entinostat with clofarabine may kill more cancer cells.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the feasibility, tolerability, toxicities, and maximum tolerated dose (MTD) of entinostat plus clofarabine for: adult patients age 40 and over with newly diagnosed, poor-risk Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) or bilineage/biphenotypic leukemia (ABL) prior to traditional cyclical multi-agent chemotherapy, and adults age 21 and over with relapsed or refractory ALL/ABL.

II. To determine if entinostat plus clofarabine can induce clinical responses in adults with newly diagnosed, poor-risk ALL/ABL and in adults with relapsed/refractory ALL/ABL.

SECONDARY OBJECTIVES:

I. To determine pharmacokinetics (PK) of entinostat alone and in combination with clofarabine.

II. To obtain descriptive preliminary pharmacodynamic (PD) data regarding the effects of entinostat alone and in combination with clofarabine on histone acetylation and global and gene specific methylation in leukemic blasts.

III. To obtain descriptive preliminary data regarding the effects of entinostat alone and in combination with clofarabine on deoxyribonucleic acid (DNA) damage and apoptosis in leukemic blasts and residual disease monitored by 6-color flow cytometry.

OUTLINE: This is a dose-escalation study of entinostat.

Patients receive entinostat orally (PO) on days 1 and 8 and clofarabine intravenously (IV) over 2 hours on days 3-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity (only for patients at least 60 years of age with newly diagnosed ALL or ABL who are unable or unwilling to tolerate standard multi-agent chemotherapy and patients with relapsed or refractory ALL or ABL).

Patients 40-59 years of age with newly diagnosed ALL receive standard multi-agent induction chemotherapy beginning on day 11. Patients at least 21 years of age in their first relapse with sensitive disease begin initiation of allogeneic transplant after one course of entinostat and clofarabine.

After completion of study treatment, patients are followed up at 30, 60, 90, 180, and 360 days. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Leukemias of Ambiguous Lineage
• Leukemia
• Leukemia, Lymphoid
• Philadelphia Chromosome
• Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent Adult Acute Lymphoblastic Leukemia
• Untreated Adult Acute Lymphoblastic Leukemia

• NCT number: NCT01132573
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 1
• Start date: April 2010