A Study of the Histone-deacetylase Inhibitor JNJ-26481585 in Patients With Advanced or Refractory Leukemia or Myelodysplastic Syndrome

NCT ID: NCT00676728

Last Updated: 2012-09-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2011-09-30

Brief Summary

The purpose of this study is to explore the safety, pharmacokinetic (what the body does to the medication), pharmacodynamic (what the medication does to the body), and activity of JNJ-26481585 in patients with advanced or refractory leukemia and myelodysplastic syndrome (MDS).

Detailed Description

This is an open-label (all people know the identity of the intervention), Phase 1 dose escalation, 2-part study (Part I and Part II). In Part I of the study, the Maximum Tolerated Dose (MTD) defined as the highest dose with an observed incidence of dose limiting toxicity (DLT) in no more than 1 in 6 patients, will be determined using rapid escalation (Stage 1) followed by conventional escalation (Stage 2). In Stage 1, at least 2 patients will be enrolled at each dose level; dose increments of 100% will be applied. In Stage 2, at least 3 patients will be enrolled at each dose level and dose increments of 20-50% will be implemented. Decisions on dose escalation or de-escalation, changes in the timing of pharmacokinetic/pharmacodynamic sampling, and the exploration of an alternative schedule were to be made by the Study Evaluation Team (SET), which consisted of all principal investigators, the medical monitor, and 1 of the sponsor's clinical pharmacologists. Part II of the study will be the expansion phase, which will begin after the MTD had been determined in Part I and an additional cohort of patients with MDS will be enrolled to further explore the safety and activity of JNJ 26481585 in patients with MDS. The starting dose for patients enrolled in Part II of the study was to be the MTD established in Part I. Depending on the outcome, the SET may decide to continue at the MTD dose, or dose-de-escalate to the next lower level (25 50% decrement from MTD). The cohort for MDS will be expanded to consist of 16 evaluable patients. Safety will be evaluated throughout the study and will include evaluations of adverse events clinical laboratory tests, electrocardiogram (ECG), vital signs, 24 hours Holter ECG, physical examination, Eastern Cooperative Oncology Group performance status and Multiple Gated Acquisition scan or echocardiography.

Conditions

Advanced or Refractory Leukemia; Myelodysplastic Syndromes

Keywords

Advanced or Refractory Leukemia; Myelodysplastic Syndromes; JNJ 26481585; Histone-Deacetylase Inhibitor; Advanced Leukemia; Refractory Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

JNJ-26481585

Group Type: EXPERIMENTAL

JNJ-26481585

Intervention Type: DRUG

In Part 1, Initial dose of JNJ-26481585 4 mg oral capsule is administered once daily on each day of a 21-day cycle. Dose will be escalated or de-escalated until Maximum tolerated dose (MTD) of JNJ-26481585 is determined in Part 1. MTD of JNJ-26481585 will be the initial dose in Part 2.

Interventions

JNJ-26481585

In Part 1, Initial dose of JNJ-26481585 4 mg oral capsule is administered once daily on each day of a 21-day cycle. Dose will be escalated or de-escalated until Maximum tolerated dose (MTD) of JNJ-26481585 is determined in Part 1. MTD of JNJ-26481585 will be the initial dose in Part 2.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed advanced or refractory acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia in blast phase, refractory chronic lymphocytic leukemia, myelodysplastic syndrome, or chronic myelomonocytic leukemia
• For Part II, patients with myelodysplastic syndrome
• Eastern Cooperative Oncology Group Performance Status Score 0, 1 or 2
• Left Ventricular Ejection Fraction greater than or equal to 50%
• Negative hepatitis B, C and human immunodeficiency virus (HIV) test within last 3 months
• Adequate liver and kidney function

Exclusion Criteria

• Known or suspected involvement of the central nervous system
• Chemotherapy (nitrosoureas and mitomycin C within 6 weeks), radiotherapy, immunotherapy or treatment with investigative agent within 3 weeks before study drug administration (except hydroxyurea which should be stopped at least 24 hours prior to first dose)
• Unstable angina or myocardial infarction within the preceding 12 months; congestive heart failure
• Poorly controlled hypertension or diabetes, ongoing active infection and psychiatric illness
• Receiving medications known to have a risk of causing QTc prolongation

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

Role: STUDY_DIRECTOR

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Locations

Baltimore, Maryland, United States

Houston, Texas, United States

Countries

United States

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=766&filename=CR013960_CSR.pdf

A Phase 1 Study of the Histone-Deacetylase Inhibitor JNJ-26481585 in Subjects with Advanced or Refractory Leukemia or Myelodysplastic Syndrome

Other Identifiers

26481585CAN1003

Identifier Type: OTHER

Identifier Source: secondary_id

CR013960

Identifier Type: -

Identifier Source: org_study_id