LymphomaPhase 1/2PCYC-0403NCT00724984
Study of the Safety and Tolerability of PCI-24781 in Patients With Lymphoma
A Phase 1/2 study testing PCI-24781 in people with Lymphoma and Hodgkin Disease, run by Pharmacyclics LLC. at 8 sites in United States.
Trial summary
The first part of the study will determine the highest dose of study drug that can be taken without causing serious side effects in patients with lymphoma. The appropriate dose determined from the first part of the study will be used in the second part of the study to assess disease response in 2 different types of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Hodgkin Disease, Lymphoma, Non-Hodgkin
- What is being tested?
- PCI-24781
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 8 sitesUnited States
- Study dates
- Jul 2008to Nov 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- • age ≥ 18 years
- Phase I: Any measurable, histologically confirmed, and previously treated lymphoma
- Phase II: Measurable, histologically confirmed, and previously treated lymphoma in one of the following categories:
- Follicular non-Hodgkin's Lymphoma
- Mantle cell lymphoma
- Ability to swallow oral capsules without difficulty
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- Estimated life expectancy > 12 weeks
- ECOG performance status ≤ 1
- Willing and able to sign a written informed consent
Who cannot join
- • 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)
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- 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 associated
- 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 evaluation.
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Vermont and Fletcher Allen Health Care
Burlington, Vermont, 05405
Northwestern University Medical School
Chicago, Illinois, 60611
Horizon Oncology Center
Lafayette, Indiana, 47905
Nebraska Methodist Hospital
Omaha, Nebraska, 68114
University of Nebraska Medical Center
Omaha, Nebraska, 68198
University of California, San Francisco
San Francisco, California, 94143
Washington University School of Medicine
St Louis, Missouri, 63110
University of Massachusetts Medical School
Worcester, Massachusetts, 01655
About this study
Official title: Phase I/II Dose-Escalation Study of the Pan-Histone Deacetylase (HDAC) Inhibitor PCI-24781 in Lymphoma
The first part of the study will determine the highest dose of study drug that can be taken without causing serious side effects in patients with lymphoma. The appropriate dose determined from the first part of the study will be used in the second part of the study to assess disease response in 2 different types of lymphoma patients.
- Conditions
- Lymphoma, Hodgkin Disease, Lymphoma, Non-Hodgkin
- Being tested
- PCI-24781
- Keywords
- 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
- Medical subject headings
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PCI-24781Drug
Phase I Dose Escalation: Up to 5 cohorts will receive PCI-24781 orally at doses starting at 30mg/m2 two times a day approximately 4-6 hours apart ("BID"), up to 90mg/m2 administered 5 days/week during the first 21 days of each 28 day cycle until the maximum tolerated dose (MTD) is reached. If a dose limiting toxicity (DLT) occurs, then the next cohort will receive PCI-24781 BID for 7 days every other week (2 times in a 28 day cycle).
Phase II Efficacy Evaluation: All patients will receive PCI-24781 orally at the dosage and regimen determined in Phase I.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: PCI-24781 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I (Dose Escalation Phase): MTD and DLTs of PCI-24781 Administered Twice Daily (BID) Measure: Disease Response
Number of patients experienced DLT in each cohort
Measured: From the Date of PCI-24781 first administration to Cycle 2 Day 1
Phase II: Overall Response Rate (CR+PR)
Measured: From first response assessment (day 22 to 28 of Cycle 2) to last response assessment on day 22-28 in even-numbered cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2008 (estimated)
- Study startJul 2008
- Primary completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharmacyclics LLC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Thorsten Graef, MD, Study director, Pharmacyclics LLC.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00724984
- Sponsor's protocol ID
- PCYC-0403
- Acronym
- PCYC-0403
- Status last verified
- Feb 2014
- First submitted
- 28 Jul 2008
- Last updated
- 7 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Buggy JJ, Cao ZA, Bass KE, Verner E, Balasubramanian S, Liu L, Schultz BE, Young PR, Dalrymple SA. CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo. Mol Cancer Ther. 2006 May;5(5):1309-17. doi: 10.1158/1535-7163.MCT-05-0442.
PubMed 16731764
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Dose-Escalation Study of the Pan-Histone Deacetylase (HDAC) Inhibitor PCI-24781 in Lymphoma
- ClinicalTrials.gov ID
- NCT00724984
- Acronym / sponsor ID
- PCYC-0403 / PCYC-0403
- Conditions
- Lymphoma, Hodgkin Disease, Lymphoma, Non-Hodgkin
- Keywords
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Pharmacyclics LLC.Industry (pharma, biotech, devices)
- Study start
- Jul 2008
- Primary completion
- Nov 2012 (actual)
- First posted
- 30 Jul 2008 (estimated)
- Results
- Posted 7 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The first part of the study will determine the highest dose of study drug that can be taken without causing serious side effects in patients with lymphoma. The appropriate dose determined from the first part of the study will be used in the second part of the study to assess disease response in 2 different types of lymphoma patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: PCI-24781 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- • age ≥ 18 years
Key exclusion criteria (24 listed)
- • 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PCI-24781Phase I Dose Escalation: Up to 5 cohorts will receive PCI-24781 orally at doses starting at 30mg/m2 two times a day approximately 4-6 hours apart ("BID"), up to 90mg/m2 administered 5 days/week during the first 21 days of each 28 day cycle until the maximum tolerated dose (MTD) is reached. If a dose limiting toxicity (DLT) occurs, then the next cohort will receive PCI-24781 BID for 7 days every other week (2 times in a 28 day cycle). Phase II Efficacy Evaluation: All patients will receive PCI-24781 orally at the dosage and regimen determined in Phase I. | Drug | 1 |
Primary outcome
Phase I (Dose Escalation Phase): MTD and DLTs of PCI-24781 Administered Twice Daily (BID) Measure: Disease Response
Time frame: From the Date of PCI-24781 first administration to Cycle 2 Day 1
Number of patients experienced DLT in each cohort
Phase II: Overall Response Rate (CR+PR)
Time frame: From first response assessment (day 22 to 28 of Cycle 2) to last response assessment on day 22-28 in even-numbered cycles
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 16731764Buggy JJ, Cao ZA, Bass KE, Verner E, Balasubramanian S, Liu L, Schultz BE, Young PR, Dalrymple SA. CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo. Mol Cancer Ther. 2006 May;5(5):1309-17. doi: 10.1158/1535-7163.MCT-05-0442.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thorsten Graef, MD study director
Pharmacyclics LLC.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PCI-24781 in people with Lymphoma and Hodgkin Disease, run by Pharmacyclics LLC. at 8 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 9 inclusion and 24 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 7 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Phase I (Dose Escalation Phase): MTD and DLTs of PCI-24781 Administered Twice Daily (BID) Measure: Disease Response (time frame: From the Date of PCI-24781 first administration to Cycle 2 Day 1). 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 NCT00724984, which also lists 1 linked publication.
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 7 Apr 2014.