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Phase I/II Dose-Escalation Study of the Pan-Histone Deacetylase (HDAC) Inhibitor PCI-24781 in Lymphoma

Phase 1/Phase 2
18 Years
Not Enrolling
Lymphoma, Hodgkin Disease, Lymphoma, Non-Hodgkin

Thank you

Trial Information

Phase I/II Dose-Escalation Study of the Pan-Histone Deacetylase (HDAC) Inhibitor PCI-24781 in Lymphoma

Inclusion Criteria:

- • age ≥ 18 years

- Phase I: Any measurable, histologically confirmed, and previously treated

- Phase II: Measurable, histologically confirmed, and previously treated lymphoma
in one of the following categories:

1. Follicular non-Hodgkin's Lymphoma

2. Mantle cell lymphoma

- Ability to swallow oral capsules without difficulty

- Estimated life expectancy > 12 weeks

- ECOG performance status ≤ 1

- Willing and able to sign a written informed consent

Exclusion Criteria:

- • More than four prior systemic treatment regimens (not counting maintenance
rituximab; salvage therapy/conditioning regimen preceding autologous bone marrow
transplantation [ABMT] and ABMT count as one regimen)

- Allogeneic bone marrow transplant

- Immunotherapy, chemotherapy, radiotherapy or experimental therapy within 4 weeks
before first day of study drug dosing

- Major surgery within 4 weeks before first day of study drug dosing

- CNS lymphoma or a history of meningeal carcinomatosis

- Prior treatment with an HDAC inhibitor (unless for treatment of Mycosis
fungoides or Sézary syndrome)

- Creatinine > 1.5 x institutional upper limit of normal (ULN) or creatinine
clearance ≤ 50 mL/min

- Total bilirubin > 1.5 x institutional ULN (unless elevated from documented
Gilbert's syndrome)

- AST and ALT > 2.5 x institutional ULN

- Platelet count < 75,000/µL for Phase I and <100,000>µL for Phase II

- Absolute neutrophil count (ANC) < 1500/µL

- Malabsorption

- Corticosteroids > 20 mg prednisone equivalent per day (topical, inhaled, or
nasal corticosteroids are permitted)

- Concurrent therapeutic anticoagulation (Phase I only)

- Uncontrolled illness including but not limited to: ongoing or active infection,
symptomatic congestive heart failure (New York Heart Association Class III or IV
heart failure), unstable angina pectoris, cardiac arrhythmia, and psychiatric
illness that would limit compliance with study requirements

- Risk factors for, or use of drugs known to prolong QTc interval or that may be

- QTc prolongation (defined as a QTc ≥ 450 msecs) or other significant ECG
abnormalities including 2nd degree AV block type II, 3rd degree AV block, or
bradycardia (ventricular rate less than 50 beats/min). If the screening ECG has
a QTc ≥ 450 msecs, the ECG can be submitted for a centralized, cardiologic

- History of myocardial infarction, acute coronary syndromes (including unstable
angina), coronary angioplasty and/or stenting within the past 6 months.

- For patients with history of myocardial infarction, congestive heart failure,
abnormal left ventricular ejection fraction (LVEF), and/or prior anthracycline
exposure, LVEF < 50%, as assessed by ventriculography (nuclear or heart
catheterization) or echocardiogram, when performed within 28 days of first dose
of study drug.

- For patients with history of coronary artery disease, a cardiac stress test
(either exercise or pharmacologic) that demonstrates clinically significant
abnormalities when performed within 28 days of first dose of study drug.

- Known HIV infection.

- Other medical or psychiatric illness or organ dysfunction which, in the opinion
of the investigator, would either compromise the patient's safety or interfere
with the evaluation of the safety of the study agent.

- Pregnant or lactating women (female patients of child-bearing potential must
have a negative serum pregnancy test within 14 days of first day of drug dosing,
or, if positive, a pregnancy ruled out by ultrasound).

- Women of child-bearing potential, or sexually active men, unwilling to use
adequate contraceptive protection during the course of the study.

Type of Study:


Study Design:

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

Outcome Measure:

Measure: Dose limiting toxicity assessment for each patient at the end of the first 28 day cycle (Phase 1) Measure: Disease response

Outcome Time Frame:

At the end of every 2 cycle

Safety Issue:


Principal Investigator

Thorsten Graef, MD

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

July 2008

Completion Date:

April 2013

Related Keywords:

  • Lymphoma
  • Hodgkin Disease
  • Lymphoma, Non-Hodgkin
  • PCI-24781
  • Lymphoma
  • Hodgkin Disease
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Follicular
  • Lymphoma, B-Cell, Marginal Zone
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymphoma, Mantle Cell
  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, T-Cell, Peripheral
  • Hodgkin Disease
  • Lymphoma
  • Lymphoma, Non-Hodgkin



Washington University School of Medicine Saint Louis, Missouri  63110
University of Nebraska Medical Center Omaha, Nebraska  68198-3330
University of California, San Francisco San Francisco, California  94143
Nebraska Methodist Hospital Omaha, Nebraska  68114
University of Massachusetts Medical School Worcester, Massachusetts  01605
Northwestern University Medical School Chicago, Illinois  60611-2927
Horizon Oncology Center Lafayette, Indiana  47905
University of Vermont and Fletcher Allen Health Care Burlington, Vermont  05405