Study of LBH589, A Deacetylase Inhibitor in Patients With Recurrent or Refractory Hodgkin or Non-Hodgkin's Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Roswell Park Cancer Institute
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01032148
First received: December 14, 2009
Last updated: July 14, 2014
Last verified: July 2014

December 14, 2009
July 14, 2014
December 2009
July 2015   (final data collection date for primary outcome measure)
Determine maximum tolerated dose (MTD) of LBH589 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01032148 on ClinicalTrials.gov Archive Site
  • Determine toxicity profile in study population [ Time Frame: 28 days after Cycle 2 Day 1 ] [ Designated as safety issue: Yes ]
  • Determine anti-lymphoma activity of LBH589 in (non-CTCL) Hodgkin's and non-Hodgkin's lymphoma patients [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Study of LBH589, A Deacetylase Inhibitor in Patients With Recurrent or Refractory Hodgkin or Non-Hodgkin's Lymphoma
Phase I Study of LBH589, A Novel Oral Deacetylase Inhibitor in Patients With Recurrent or Refractory Hodgkin or Non-Hodgkin's Lymphoma

The purpose of this study is to find out the effects of a drug called LBH589 when given to people with recurrent or refractory Hodgkin or Non-Hodgkin's lymphoma. The safety of this drug will also be studied. The participants' physical state, changes in the size of the tumor, or state of Hodgkin or non-Hodgkin's Lymphoma, and laboratory findings taken while on-study will help the researchers decide if LBH589 is safe and effective.

This is an open-label, standard 3-3 dose finding scheme with a modification that allows intra-patient dose modification to determine maximum tolerated dose and toxicity profile of LBH589 in patients with recurrent or refractory Hodgkin's or non-Hodgkin's lymphoma.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hodgkin's Lymphoma
  • Non-Hodgkin's Lymphoma
Drug: LBH589
LBH589 will be administered orally as once daily dose of 20 mg po q M, W, F on a q28 day cycle.
Experimental: LBH589
LBH589 administered orally as once daily dose of 20 mg po q M, W, F on a q 28 day cycle, escalating to a maximum dase of 60 mg
Intervention: Drug: LBH589
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
33
July 2015
July 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male or female patients age ≥ 18 years old with relapsed/refractory Hodgkin lymphoma or NHL patients who have relapsed or are refractory after receiving a minimum of two prior therapies
  • Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed

Laboratory requirements:

  • ANC ≥ 1.5 x 10(9th)/L, unless due to bone marrow involvement with lymphoma
  • Hemoglobin ≥ 9 g/dl without packed red blood cell dependency, unless due to bone marrow involvement with lymphoma
  • Platelets ≥ 100 x 10(9th)/L, unless due to bone marrow involvement with lymphoma
  • Serum creatinine ≤ 1.5 x Upper limit of Normal, or calculated Creatinine Clearance ≥ 50 mL/min
  • AST and ALT ≤ 2.5 x Upper limit of Normal, unless due to liver involvement with lymphoma
  • Serum bilirubin ≤ 1.5 x Upper limit of Normal
  • Albumin > 3.0 g/dl
  • Serum potassium ≥ Lower limit of Normal
  • Total serum calcium [corrected for serum albumin] or ionized calcium ≥ Lower limits of normal
  • Serum magnesium ≥ Lower limit of Normal
  • Serum phosphorus ≥ Lower limit of Normal
  • TSH ≥ LLN and free T4 within normal limits. Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
  • Baseline MUGA or ECHO must demonstrate LVEF ≥ 50%
  • ECOG Performance Status of ≤ 2

Exclusion Criteria:

  • Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
  • Patients who will need valproic acid for any medication during the study or within 5 days prior to first LBH589 treatment
  • Peripheral neuropathy ≥ CTCAE grade 1
  • Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
  • Patients with congenital QT syndrome
  • History or presence of sustained ventricular tachyarrhythmia.
  • Any history of ventricular fibrillation or torsade de pointes
  • Bradycardia defined as Heart Rate < 50 bpm. Patients with pacemakers are eligible if Heart Rate ≥ 50 bpm
  • Screening EKG with a QTc.450msec
  • Right Bundle branch block + left anterior hemiblock (bifascicular block)
  • Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug
  • other clinically significant heart disease (e.g. CHF NY Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension or history of poor compliance with an antihypertensive regimen)
  • Impairment of GI function or GI disease that may significantly alter the absorption of LBH589
  • Patients with Diarrhea > CTCAE grade 1
  • Other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values that could cause unaccepted safety risks or compromise compliance with the protocol
  • Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
  • Concomitant use of CYP3A4 inhibitors
  • Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites(which ever is longer) and who have not recovered from side effects of those therapies
  • Patients who have received either immunotherapy within ≤ 8 weeks;chemotherapy within ≤ 4 weeks or radiation therapy to >30% of marrow-bearing bone within ≤ weeks prior to starting study treatment or who have not yet recovered from side effects of such therapies
  • Patients with an active bleeding tendency or is receiving any treatment with therapeutic doses of sodium warfarin or coumadin derivatives. Low doses of Coumadin (e.g.≤2 mg/day) to maintain line patency is allowed.
  • Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Women who are pregnant or breast feeding or women of childbearing potential not using effective method of birth control
  • Male patients whose sexual partners are women of childbearing potential not using effective birth control
  • Patients with prior malignancy within 5 years (except for basal or squamous cell carcinoma, in situ cancer of the cervix or early stage prostate or bladder carcinomas)
  • Patients with known positivity for HIV or hepatitis C: baseline testing for HIV and Hepatitis C is not required
  • Prior allogenic stem cell transplant
  • Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff
  • Patients taking CYP2D6 inhibitors should be carefully monitored, but these drugs are not necessarily contraindicated when use concomitantly with LBH. Use of these drugs is not an exclusion criterion
Both
18 Years and older
No
Contact: AskRPCI 1-877-275-7724 AskRPCI@roswellpark.org
United States
 
NCT01032148
RPCI I 147408
Yes
Roswell Park Cancer Institute
Roswell Park Cancer Institute
Novartis
Principal Investigator: Myron Czuczman, MD Roswell Park Cancer Institute
Roswell Park Cancer Institute
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP