Relapsed LymphomasPhase 1/2NCT00785798
Vorinostat and Pegylated Liposomal Doxorubicin in Relapsed or Refractory Lymphomas
A Phase 1/2 study testing Vorinostat and Pegylated Liposomal Doxorubicin (PLD), Doxil in people with Relapsed Lymphomas and Refractory Lymphomas, run by Yale University at 1 site in United States.
Trial summary
The study will be a dose-finding, phase I study of the combination of vorinostat and PLD in patients with advanced lymphoma refractory to at least one prior systemic therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Lymphomas, Refractory Lymphomas
- What is being tested?
- Vorinostat and Pegylated Liposomal Doxorubicin (PLD), Doxil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to Sep 2011
- 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
- Patients must have histologically confirmed lymphoma in relapse or refractory to at least one prior systemic therapy. However, patients should be in relapse or refractory to appropriate standard salvage therapy, or have declined or are not deemed eligible for treatment with such salvage therapy including stem cell transplant. Diseases such as T-cell lymphomas, for which there is no standard salvage therapy, may enroll after failing only one prior systemic therapy.
- Patient must have measurable disease within lymph nodes, skin, or leukemic involvement of lymphoma
- Patient must have performance status of ≤2 on the ECOG Performance Scale. (See Section 6.1)
- Prior treatment with an anthracycline is permitted as long as the total doxorubicin dose (or equivalent) does not exceed 450mg/m2.
- Patients must have normal cardiac function, as evidenced by a left ventricular ejection fraction (LVEF) > 50%. A MUGA scan (echocardiogram may be used if MUGA scan is not available, but the same test must be used throughout the study) to evaluate LVEF must be done within 2 weeks prior to first dose of study drug.
- Patients with a minimum of 3 weeks since their last systemic treatment. Patients who have had prior treatment with an HDAC inhibitor may enroll after a 30-day washout period.
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- Patients ≥ 18 years of age of any race, sex, and ethnicity
- Life expectancy of greater than 12 weeks.
- Female patient of childbearing potential has a negative serum pregnancy test β-hCG within 96 hours prior to receiving the first dose of vorinostat.
- Female patients with reproductive potential must use an adequate contraceptive method (e.g., abstinence, intrauterine device, oral contraceptives, barrier device with spermicide or surgical sterilization) during treatment and for three months after completing treatment.
- Male patient agrees to use an adequate method of contraception for the duration of the study.
- Patient must have adequate organ function as indicated by the following laboratory values:
- System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥1000 /mcL Platelets ≥75,000 /mcL Hemoglobin ≥ 9 g/dL Coagulation Prothrombin Time or INR ≤1.5x upper limit of normal (ULN) unless receiving therapeutic anticoagulation Partial thromboplastin time (PTT) ≤1.5x the ULN unless the patient is receiving therapeutic anticoagulation.
- Chemistry K levels Normal limits Mg levels Normal limits Renal Serum creatinine or calculated creatinine clearance ≤2.0mg/dL OR ≥40 mL/min for patients with creatinine levels > 2.0mg/dL Hepatic Serum total bilirubin Normal limits AST (SGOT) and ALT (SGPT) ≤ 3 X ULN Alkaline Phosphatase (liver fraction) ≤ 3 X ULN a Creatinine clearance should be calculated per institutional standard.
- Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent.
- Patient is ≥18 years of age on day of signing informed consent.
- Patient is available for periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study.
- Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of vorinostat will be determined following review of their case by the Principal Investigator.
Who cannot join
- Patients with previously untreated lymphoma
- Patient who has had chemotherapy, radiotherapy, or biological therapy within 3 weeks prior to initial dosing with study drugs or who has not recovered from adverse events due to agents administered more than 3 weeks earlier.
- Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drugs.
- Myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
- QTc prolongation greater than 500ms
- Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for >5 years or are considered by their physician to be at less than 30% risk of relapse.
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- Patient is on any systemic steroids that have not been stabilized during the 3 weeks prior to the start of the study drugs.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or doxorubicin.
- History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin HCL or the components of PLD.
- Patients with active CNS metastases and/or carcinomatous meningitis are excluded. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids or on a stable dose of steroids.
- Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse.
- Patient is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study. Pregnant women are excluded from this study because vorinostat and doxorubicin have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat or PLD, breastfeeding should be discontinued if the mother is treated with vorinostat and PLD.
- Patient has uncontrolled intercurrent illness or circumstances that could limit compliance with the study, including, but not limited to the following: active infection, acute or chronic graft versus host disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric conditions.
- Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate.
- Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs.
- HIV-positive patients receiving combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with vorinostat.
- Patients with known history of Hepatitis B or C are excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale University School of Medicine
New Haven, Connecticut, 06520
About this study
Official title: A Phase I/II Trial of Vorinostat and Pegylated Liposomal Doxorubicin in Relapsed or Refractory Lymphomas
The study will be a dose-finding, phase I study of the combination of vorinostat and PLD in patients with advanced lymphoma refractory to at least one prior systemic therapy.
Read the detailed description
The study will also be a dose-escalating study of vorinostat 200mg to 400 mg twice daily for 7 days with PLD 30mg/m2 on day 3 every 21 days, with intrapatient dose escalation.
Primary endpoint is progression. All endpoints are observational
- Conditions
- Relapsed Lymphomas, Refractory Lymphomas
- Being tested
- Vorinostat, Pegylated Liposomal Doxorubicin (PLD), Doxil
- Keywords
- Relapsed Lymphomas, Refractory Lymphomas
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorinostatDrug
Also called ZOLINZA
200mg to 400 mg twice daily on days 1-7
Pegylated Liposomal Doxorubicin (PLD), DoxilDrug
Also called DOXIL
IV 30mg/m2 on day 3 of a 21-day cycle
| Study group | Role | What they receive |
|---|---|---|
| vorinostat doxil | Experimental | Escalating doses of vorinostat 200mg to 400mg twice daily on days 1-7, and fixed-dose IV PLD 30mg/m2 on day 3 of a 21-day cycle Receives: Drug: Vorinostat; Drug: Pegylated Liposomal Doxorubicin (PLD), Doxil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
number of patients responding
Measured: end of study (up to 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2008 (estimated)
- Study startJan 2009
- Primary completionSep 2011
- Study completionSep 2011
Why it stopped: sponsor requested
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.
- Other trials for Relapsed LymphomasStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Francine Foss, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00785798
- Sponsor's protocol ID
- 0711003269
- Status last verified
- Mar 2022
- First submitted
- 4 Nov 2008
- Last updated
- 4 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Vorinostat and Pegylated Liposomal Doxorubicin in Relapsed or Refractory Lymphomas
- ClinicalTrials.gov ID
- NCT00785798
- Acronym / sponsor ID
- 0711003269
- Conditions
- Relapsed Lymphomas, Refractory Lymphomas
- Keywords
- Relapsed Lymphomas, Refractory Lymphomas
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: sponsor requested
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Jan 2009
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 5 Nov 2008 (estimated)
- Results
- Posted 27 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will be a dose-finding, phase I study of the combination of vorinostat and PLD in patients with advanced lymphoma refractory to at least one prior systemic therapy.
Detailed description
The study will also be a dose-escalating study of vorinostat 200mg to 400 mg twice daily for 7 days with PLD 30mg/m2 on day 3 every 21 days, with intrapatient dose escalation.
Primary endpoint is progression. All endpoints are observational
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| vorinostat doxil | Experimental | Drug: Vorinostat, Drug: Pegylated Liposomal Doxorubicin (PLD), DoxilEscalating doses of vorinostat 200mg to 400mg twice daily on days 1-7, and fixed-dose IV PLD 30mg/m2 on day 3 of a 21-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have histologically confirmed lymphoma in relapse or refractory to at least one prior systemic therapy. However, patients should be in relapse or refractory to appropriate standard salvage therapy, or have declined or are not deemed eligible for treatment with such salvage therapy including stem cell transplant. Diseases such as T-cell lymphomas, for which there is no standard salvage therapy, may enroll after failing only one prior systemic therapy.
- Patient must have measurable disease within lymph nodes, skin, or leukemic involvement of lymphoma
- Patient must have performance status of ≤2 on the ECOG Performance Scale. (See Section 6.1)
- Prior treatment with an anthracycline is permitted as long as the total doxorubicin dose (or equivalent) does not exceed 450mg/m2.
- Patients must have normal cardiac function, as evidenced by a left ventricular ejection fraction (LVEF) > 50%. A MUGA scan (echocardiogram may be used if MUGA scan is not available, but the same test must be used throughout the study) to evaluate LVEF must be done within 2 weeks prior to first dose of study drug.
Key exclusion criteria (18 listed)
- Patients with previously untreated lymphoma
- Patient who has had chemotherapy, radiotherapy, or biological therapy within 3 weeks prior to initial dosing with study drugs or who has not recovered from adverse events due to agents administered more than 3 weeks earlier.
- Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drugs.
- Myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
- QTc prolongation greater than 500ms
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 |
|---|---|---|
| VorinostatAlso: ZOLINZA200mg to 400 mg twice daily on days 1-7 | Drug | vorinostat doxil |
| Pegylated Liposomal Doxorubicin (PLD), DoxilAlso: DOXILIV 30mg/m2 on day 3 of a 21-day cycle | Drug | vorinostat doxil |
Primary outcome
Overall Response Rate
Time frame: end of study (up to 2 years)
number of patients responding
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Francine Foss, MD principal investigator
Yale University
1 site 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 Vorinostat and Pegylated Liposomal Doxorubicin (PLD), Doxil in people with Relapsed Lymphomas and Refractory Lymphomas, run by Yale University at 1 site 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 18 inclusion and 18 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: stopped early, as of the sponsor's last update on 4 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 27 Jul 2016). 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?
Overall Response Rate (time frame: end of study (up to 2 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Apr 2022.