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LeukemiaPhase 1NCT00686218

Panobinostat (LBH589) and Imatinib Mesylate in Treating Patients With Previously Treated Chronic Phase Chronic Myelogenous Leukemia

A Phase 1 study testing imatinib mesylate, panobinostat and polymerase chain reaction in people with Leukemia, run by City of Hope Medical Center at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Panobinostat and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with imatinib in treating patients with previously treated chronic phase… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia
What is being tested?
imatinib mesylate, panobinostat and polymerase chain reaction
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
3 sitesUnited States
Study dates
May 2008to Aug 2014
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

  • Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
  • CML CP patients who have been treated with and tolerated Imatinib for 1 year or more, have achieved at least major cytogenetic response and continue to be BCR-ABL positive (Patients should be receiving Imatinib at a dose of 400 daily at the time of entry into the study)
  • ANC and PLT need to be in the normal range
  • Serum albumin >= 3g/dL
  • AST/SGOT and ALT/SGPT =< 2.5 x upper limit of normal (ULN)
  • Serum bilirubin =< 1.5 x ULN
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  • Serum creatinine =< 1.5 x ULN or 24-hour creatinine clearance >= 50 ml/min
  • Serum potassium >= lower limit of normal (LLN)
  • Serum phosphorus >= LLN
  • Serum total calcium (corrected for serum albumin) or serum ionized calcium >= LLN
  • Serum magnesium >= LLN
  • ECOG performance status of =< 2

Who cannot join

  • Prior treatment with an HDAC inhibitor
  • Patient who have been treated with Imatinib < 1 year or patients are currently being treated with Imatinib at a dose > 400 mg daily
  • Impaired cardiac function including any one of the following: Screening ECG with a QTc > 450 msec; Patients with congenital long QT syndrome; History or presence of sustained ventricular tachycardia; Any history of ventricular fibrillation or torsades de pointes; Bradycardia defined as heart rate < 50 beats per minute (patients with a pacemaker and heart rate >= 50 beats per minute are eligible); Patients with a myocardial infarction or unstable angina within 6 months of study entry; Congestive heart failure (NY Heart Association class III or IV); Right bundle branch block and left anterior hemiblock (bifascicular block)
  • Uncontrolled hypertension
  • Concomitant use of drugs with a risk of prolonging the QT interval or inducing torsades de pointes
  • Concomitant use of CYP3A4 inhibitors
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  • Patients with unresolved diarrhea > CTCAE grade 1
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
  • Other concurrent severe and/or uncontrolled medical conditions
  • Patients who have received chemotherapy, any investigational drug or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Concomitant use of any other anti-cancer therapy or radiation therapy
  • Patients being treated with Coumadin (unless patients who require anticoagulation can be switched to a low-molecular weight or standard heparin)
  • Female patients who are pregnant or breast feeding or patients of reproductive potential not willing to use a double method of contraception including a barrier method (i.e. condom) during the study and 3 months after the end of treatment (Women of childbearing potential [WOCBP] must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589)
  • Male patients whose sexual partners are WOCBP not willing to use a double method of contraception including condom during the study and 3 months after the end of treatment
  • Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin
  • Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
  • Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • City of Hope Medical Center

    Duarte, California, 91010-3000

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

  • South Pasadena Cancer Center

    South Pasadena, California, 91030

Other trials in United States

About this study

Official title: A Phase I Dose Escalation Study of LBH589 in Combination With Imatinib Mesylate for Patients With Chronic Myeloid Leukemia in Cytogenetic Remission With Residual Disease Detectable by Q-PCR

RATIONALE: Panobinostat and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with imatinib in treating patients with previously treated chronic phase chronic myelogenous leukemia.

Read the detailed description

OBJECTIVES:

Primary

  • To determine the safety and tolerability of LBH589 given in combination with imatinib mesylate in CML patients who are in Major Cytogenetic Remission (MCR) with residual BCR-ABL positive cells after at least 1 year of daily imatinib mesylate treatment.
  • To determine the maximum tolerated dose (MTD) and dose-limiting toxicity of LBH589 given in combination with imatinib mesylate in CML patients.

Secondary

  • To study the effect of LBH589 given in combination with imatinib mesylate on cytogenetic response status and BCR-ABL levels in CML patients in major cytogenetic remission on imatinib mesylate treatment.

Tertiary

  • To study the effect of LBH589 given in combination with imatinib mesylate on residual BCR-ABL positive primitive progenitors in CML patients in major cytogenetic remission on imatinib mesylate treatment.

OUTLINE: This is dose-escalation study of panobinostat.

Patients receive oral panobinostat once daily on days 1, 3 and 5; 8, 10, and 12; 15, 17, and 19; and 22, 24, and 26. Patients also receive oral imatinib mesylate once daily on days 1-28. Treatment repeats every 21 or 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 month and then every 3 months for up to 1 year.

Conditions
Leukemia
Being tested
imatinib mesylate, panobinostat, polymerase chain reaction, protein expression analysis, western blotting
Keywords
chronic phase chronic myelogenous leukemia
Medical subject headings
Leukemia, Leukemia, Myeloid, Chronic-Phase

What participants receive

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

  • imatinib mesylateDrug

    Also called CGP 57148, Gleevec, Glivec

    Given orally

  • panobinostatDrug

    Also called Faridak, HDAC inhibitor LBH589, histone deacetylase inhibitor LBH589, LBH589

    Given orally

  • polymerase chain reactionGenetic

    Testing

  • protein expression analysisGenetic

    Testing

  • western blottingGenetic

    Testing

  • flow cytometryOther

    Testing

  • laboratory biomarker analysisOther

    Testing

  • pharmacological studyOther

    Testing

Study groups in NCT00686218
Study groupRoleWhat they receive
Treatment (panobinostat, imatinib mesylate)ExperimentalPatients receive oral panobinostat once daily on days 1, 3 and 5; 8, 10, and 12; 15, 17, and 19; and 22, 24, and 26. Patients also receive oral imatinib mesylate once daily on days 1-28. Treatment repeats every 21 or 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: imatinib mesylate; Drug: panobinostat; Genetic: polymerase chain reaction; Genetic: protein expression analysis; Genetic: western blotting; Other: flow cytometry; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

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

  1. Maximum tolerated dose of histone deacetylase inhibitor LBH589 in combination with imatinib mesylate

    Measured: 1 month

  2. Safety and tolerability of histone deacetylase inhibitor LBH589 in combination with imatinib mesylate

    Measured: 4 months

Secondary outcomes (2)

  1. Effect of treatment with histone deacetylase inhibitor LBH589 in combination with imatinib mesylate on cytogenetic response status and BCR-Abl levels

    Measured: 4 months

  2. Effect of treatment with histone deacetylase inhibitor LBH589 in combination with imatinib mesylate on residual BCR-Abl positive primitive progenitors

    Measured: 4 months

Timeline

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

  1. First posted29 May 2008 (estimated)
  2. Study startMay 2008
  3. Primary completionMar 2013
  4. Study completionAug 2014

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
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00686218
Sponsor's protocol ID
07203
Other IDs
P30CA033572, NOVARTIS-CSTI571AUS275T, CDR0000596065, NCI-2010-00528
Status last verified
Aug 2014
First submitted
28 May 2008
Last updated
15 Aug 2014
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing imatinib mesylate, panobinostat and polymerase chain reaction in people with Leukemia, run by City of Hope Medical Center at 3 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 12 inclusion and 17 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: finished, as of the sponsor's last update on 15 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum tolerated dose of histone deacetylase inhibitor LBH589 in combination with imatinib mesylate (time frame: 1 month). The study lists 2 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 NCT00686218.

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 15 Aug 2014.

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