Belinostat and Azacitidine in Treating Patients With Advanced Hematologic Cancers or Other Diseases

NCT00351975 | Completed Phase 1

• 10 other identifiers: NCI-2009-00146UCCRC-14510ANCI-7285CDR000048641814510A7285U01CA069852U01CA132123P30CA014599U01CA062491
• Study Type: interventional
• Target: 56
• Locations: 3 countries
• Sites: 4

Brief Summary

This phase I trial is studying the side effects and best dose of belinostat when given together with azacitidine in treating patients with advanced hematologic cancers or other diseases. Belinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving belinostat together with azacitidine may kill more cancer cells.

Conditions

Accelerated Phase of Disease; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndrome; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of belinostat in combination with azacitidine

  Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 or 4.0.

  Course 1 (28 days)

Secondary Outcomes (3)

• Changes in pharmacodynamic variables (target gene expression, apoptosis)

  Course 1 (baseline to day 5)

• Association of methylation status, categorized as positive or negative, with changes in target gene expression

  Baseline, days 4 or 5, and days 25-28

• Clinical activity (complete remission, partial remission, stable disease, hematologic improvement)

  After 4, 8, and 16 weeks

Study Arms (2)

Arm I (chemotherapy)

EXPERIMENTAL

Patients receive azacitidine SC on days 1-5.

Drug: Azacitidine; Other: Laboratory Biomarker Analysis

Arm II (chemotherapy, enzyme inhibitor therapy)

EXPERIMENTAL

Patients receive azacitidine as in arm I and belinostat at the MTD IV over 30 minutes on days 1-5.

Drug: Belinostat; Drug: Azacitidine; Other: Laboratory Biomarker Analysis

Interventions

Belinostat DRUG

Given IV

Also known as: Beleodaq, PXD 101, PXD101

Arm II (chemotherapy, enzyme inhibitor therapy)

Azacitidine DRUG

Given SC

Also known as: 5-AC, 5-AZC, U-18496

Arm I (chemotherapy); Arm II (chemotherapy, enzyme inhibitor therapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (chemotherapy); Arm II (chemotherapy, enzyme inhibitor therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of 1 of the following:
• Relapsed or refractory acute myeloid leukemia (AML)
• Relapsed or refractory acute promyelocytic leukemia (must have failed both tretinoin and arsenic trioxide)
• Relapsed or refractory acute lymphoblastic leukemia
• Secondary AML, including AML arising from antecedent hematologic diseases, such as myelodysplastic syndromes (MDS) or myeloproliferative disorders, OR therapy-related AML
• Chronic myelogenous leukemia in accelerated or blast phase
• Advanced phases of Philadelphia chromosome-negative (Ph-) chronic myeloproliferative disorders, as defined by ≥ 1 of the following:
• Presence of anemia (hemoglobin \< 10 g/dL and/or red blood cell transfusion dependent)
• Presence of palpable splenomegaly
• MDS, including chronic myelomonocytic leukemia
• Must have intermediate or high-risk International Prognostic Scoring System (IPSS) scores (≥ 0.5)
• Low-risk IPSS scores allowed provided ≥ 1 of the following criteria are met:
• Hemoglobin \< 10 g/dL and/or red blood cell transfusion dependent
• Platelet count \< 50,000/mm³
• Absolute neutrophil count \< 1,000/mm³

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Princess Margaret Hospital

Cashmere, Canterbury, 8022, New Zealand

Location

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Acute; Leukemia, Promyelocytic, Acute; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Blast Crisis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Myeloproliferative Disorders; Primary Myelofibrosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Recurrence

Interventions

belinostat; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Olatoyosi Odenike

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2006
• First Posted: July 14, 2006
• Study Start: June 1, 2006
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: December 23, 2014

Record last verified: 2013-10

Locations

US (2); CA (1); NZ (1)