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

Phase 1
18 Years
Open (Enrolling)
Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma

Thank you

Trial Information

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

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.

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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine maximum tolerated dose (MTD) of LBH589

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Myron Czuczman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Food and Drug Administration

Study ID:

RPCI I 147408



Start Date:

December 2009

Completion Date:

July 2013

Related Keywords:

  • Hodgkin's Lymphoma
  • Non-Hodgkin's Lymphoma
  • Recurrent
  • Refractory
  • Hodgkin Disease
  • Lymphoma
  • Lymphoma, Non-Hodgkin



Roswell Park Cancer InstituteBuffalo, New York  14263