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Advanced or Refractory LeukemiaPhase 1NCT00676728

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

A Phase 1 study testing JNJ-26481585 in people with Advanced or Refractory Leukemia and Myelodysplastic Syndromes, run by Johnson & Johnson Pharmaceutical Research & Development, L.L.C. at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
JNJ-26481585
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
2 sitesUnited States
Study dates
Dec 2008to Sep 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Study site

    Baltimore, Maryland

  • Study site

    Houston, Texas

Other trials in United States

About this study

Official title: A Phase 1 Study of the Histone-deacetylase Inhibitor JNJ-26481585 in Subjects With Advanced or Refractory Leukemia or Myelodysplastic Syndrome

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).

Read the 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.

Being tested
JNJ-26481585
Keywords
Advanced or Refractory Leukemia, Myelodysplastic Syndromes, JNJ 26481585, Histone-Deacetylase Inhibitor, Advanced Leukemia, Refractory Leukemia
Medical subject headings
Leukemia, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • JNJ-26481585Drug

    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.

Study groups in NCT00676728
Study groupRoleWhat they receive
JNJ-26481585ExperimentalNot described
Receives: Drug: JNJ-26481585

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of patients with adverse events

    Measured: Upto 14 days after last dose administration of study medication

  2. Number of patients with dose limiting toxicity [DLT]

    Only toxicities that occur during Treatment Cycle 1 will be used for the purposes of defining DLT.

    Measured: From the date of dosing upto 3 months after the date the last patient enrolled in Part I of the study, received the first dose of study medication

  3. Maximum tolerated dose (MTD) of JNJ 26481585

    The MTD is defined as the highest dose with an observed incidence of DLT in no more than 1 in 6 patients.

    Measured: From the date of dosing upto 3 months after the date the last patient enrolled in Part I of the study, received the first dose of study medication

Secondary outcomes (13)

  1. Maximum plasma concentration (Cmax) of JNJ 26481585

    Measured: Days 1, 2, 8, 15 and 21 of Cycle 1

  2. Time to reach maximum plasma concentration (tmax) of JNJ-26481585

    Measured: Days 1, 2, 8, 15 and 21 of Cycle 1

  3. Area under the plasma concentration-time curve from time 0 to 24 hours (AUC0-24)

    Measured: Days 1, 2, 8, 15 and 21 of Cycle 1

  4. Elimination half-life (t1/2) of JNJ-26481585

    Measured: Days 1, 2, 8, 15 and 21 of Cycle 1

  5. Cumulative amount of drug excreted in urine over 24 hours (Ae24)

    Measured: Days 1 and 21 of Cycle 1

  6. Renal clearance (CLR) of JNJ 26395018

    Measured: Days 1 and 21 of Cycle 1

  7. Concentration of biomarker histone acetylation

    Measured: Days 1 and 21 of Cycle 1; Day 21 of Cycles 2 to 20

  8. Concentration of biomarker interleukin-6 (IL-6)

    Measured: Days 1 and 21 of Cycle 1; Day 21 of Cycles 2 to 20

  9. Concentration of biomarker heat shock protein 90 (Hsp90)

    Measured: Days 1 and 21 of Cycle 1; Day 21 of Cycles 2 to 20

  10. Complete Blood Count (CBC)

    Anticancer activity of JNJ-26481585 explored by assessment of response parameters such as CBC.

    Measured: Pre-treatment (within 4 weeks prior to first dose of JNJ-26481585); Days 1, 3, 8, 15 and 21 of Cycle 1; Days 8, 15 and 21 of Cycle 2; Day 21 of Cycle 3 to 20; follow up (within 14 days after last dose of JNJ-26481585)

  11. Assessment of Transfusion Record

    Assessment of Transfusion Record is the parameter for assessment of response.

    Measured: From Day 1 of Cycle 1 upto 14 days after last dose

  12. Radiological Tumor Mass assessment

    Radiological Tumor Mass assessment is the parameter for assessment of response.

    Measured: Pre-treatment, Day 21 of Cycle 2 to 20 and follow up

  13. Bone marrow aspirate/biopsy assessment

    Bone marrow aspirate/biopsy assessment is the parameter for assessment of response.

    Measured: Pre-treatment, Day 21 of Cycles 1 to 20

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 May 2008 (estimated)
  2. Study startDec 2008
  3. Primary completionSep 2011
  4. Study completionSep 2011

Why it stopped: Sponsor Decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00676728
Sponsor's protocol ID
CR013960
Other IDs
26481585CAN1003
Status last verified
Sep 2012
First submitted
8 May 2008
Last updated
14 Sep 2012
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing JNJ-26481585 in people with Advanced or Refractory Leukemia and Myelodysplastic Syndromes, run by Johnson & Johnson Pharmaceutical Research & Development, L.L.C. at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of patients with adverse events (time frame: Upto 14 days after last dose administration of study medication). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00676728.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2012.

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