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A Phase I/II Trial of Vorinostat and Pegylated Liposomal Doxorubicin in Relapsed or Refractory Lymphomas

Phase 1/Phase 2
18 Years
Open (Enrolling)
Relapsed Lymphomas, Refractory Lymphomas

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Trial Information

A Phase I/II Trial of Vorinostat and Pegylated Liposomal Doxorubicin in Relapsed or Refractory Lymphomas

Inclusion Criteria:

- 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

- 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

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.

Exclusion Criteria:

- 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

- 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.

- 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.

Type of Study:


Study Design:

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

Outcome Measure:

To determine the recommended dosing and safety and tolerability for the combination of vorinostat and PLD in patients with relapsed or refractory lymphoma

Outcome Time Frame:

Upon completion of Phase 1 of study

Safety Issue:


Principal Investigator

Francine Foss, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Yale University


United States: Institutional Review Board

Study ID:




Start Date:

January 2009

Completion Date:

November 2010

Related Keywords:

  • Relapsed Lymphomas
  • Refractory Lymphomas
  • Relapsed Lymphomas
  • Refractory Lymphomas
  • Lymphoma



Yale University School Of MedicineNew Haven, Connecticut  06520