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A Single Agent Phase II Study of Depsipeptide (FK228) in the Treatment of Cutaneous T-cell Lymphoma


Phase 2
18 Years
N/A
Not Enrolling
Both
Cutaneous T-cell Lymphoma

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Trial Information

A Single Agent Phase II Study of Depsipeptide (FK228) in the Treatment of Cutaneous T-cell Lymphoma


Responses were evaluated according to a composite assessment (Objective Primary Disease
Response Evaluation Criteria [OPDREC]) that included cutaneous manifestations of disease,
lymph node involvement, and circulating malignant T-cells (Sézary cells). Skin involvement
was measured using a weighted body surface area skin assessment tool (WBSA/SWAT) or an
erythroderma score, depending upon the pt's disease. Disease response was assessed by the
Investigators and an Independent Response Review Committee (IRRC) with the IRRC assessment
considered supportive of the Investigator's evaluations using the following criteria:

Complete Response (CR):

- Complete resolution of skin patches, skin plaques, and skin tumors, or erythroderma

- No evidence of abnormal lymph nodes

- Absence of circulating Sézary cells.

- No evidence of new tumors (cutaneous or non-cutaneous)

- Findings confirmed by skin biopsy

Clinical complete response (CCR):

- Same as CR but without skin biopsy

Partial Response (PR):

- ≥50% improvement in the summation of (change in Skin + change in Lymph Node + change in
Peripheral Blood) with

- At least >30% improvement in Skin and

- No worsening in Lymph Node or Sézary cells.

- No evidence of new tumors (cutaneous/non-cutaneous)

Stable Disease (SD):

- Not enough improvement or worsening in the summation of (change in Skin + change in
Lymph Node + change in Peripheral Blood to qualify as PR or PD

- No evidence of new tumors (cutaneous/non-cutaneous)

SD90:

- SD90 was defined as documented evidence of SD for at least 90 Days Duration

Progressive Disease (PD):

- Evidence of new tumor (cutaneous or non-cutaneous), OR

- >25% worsening in the summation of (change in Skin + change in Lymph Node + change in
Peripheral Blood) with >15% worsening in change in Skin.


Inclusion Criteria:

Patients had to fulfill all of the following criteria to be eligible
for study participation:

- Males or non-pregnant females aged 18 or over.

- Histologically confirmed diagnosis of CTCL, including mycosis fungoides and Sézary
syndrome.

- Patients with CTCL stages II-A, II-B, III, and IV-A only.

- Patients with CTCL stage IB who had relapsed following previous therapy and where, in
the investigator's opinion, the potential benefit of treatment with romidepsin
outweighed the possible risks.

- Patients who had failed standardized skin-directed therapy and had had at least one
course of systemic therapy, such as interferon, Ontak®, chemotherapy or Targretin®,
etc., which they were deemed to have failed.

- Anticipated life expectancy greater than six months.

- Written informed consent to participate in the study.

Exclusion Criteria: Patients were ineligible for entry if any of the following criteria
were met:

- ECOG Performance Status >1.

- Patients who had not received at least 1 course of prior systemic therapy for CTCL.

- Visceral involvement i.e. Stage 4B disease (lymphadenopathy was allowed).

- Patients with known cardiac abnormalities such as:

- Congenital long QT syndrome

- QTc (Corrected QT interval on ECG) interval >480 milliseconds

- Any cardiac arrhythmia requiring anti-arrhythmic medication.

- Patients who had had a myocardial infarction within 12 months of study entry.

- Patients who had a history of coronary artery disease (CAD) e.g. angina Canadian
class II to IV. In any patient in whom there was doubt, the patient should have had
a stress imaging study and exercise electrocardiogram (ECG) and, if abnormal,
angiography to define whether or not CAD was present.

- Patients with an ECG recorded at screening showing evidence of cardiac ischaemia (ST
depression of >=2 mm). If in any doubt, the patient should have had a stress imaging
study and exercise ECG and, if abnormal, angiography to define whether or not CAD is
present.

- Patients with congestive heart failure that met New York Heart Association class II
to IV definitions and/or ejection fraction <40% by multiple gated acquisition (MUGA)
scan or <50% by echocardiogram and/or magnetic resonance imaging (MRI)

- Patients with a history of sustained ventricular tachycardia (VT), ventricular
fibrillation (VF), Torsade de Pointes, or cardiac arrest, unless currently addressed
with an automatic implantable cardioverter defibrillator (AICD).

- Patients with hypertrophic cardiomegaly or restrictive cardiomyopathy from prior
treatment or other causes (if in doubt, see ejection fraction criteria above).

- Patients with uncontrolled hypertension, i.e. >=160/95 mmHg.

- Concomitant use of any anti-cancer therapy.

- Concomitant use of warfarin (due to a drug interaction).

- Concomitant use of any investigational agent.

- Use of any investigational agent within 4 weeks of study entry.

- Concomitant use of drugs which may cause a prolongation of the QTc interval.

- Patients with a potassium level of <3.5 mmol/L and a magnesium level of <0.8 mmol/L.

- Clinically significant active infection.

- Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.

- Inadequate bone marrow or other organ function, as evidenced by:

- unsupported haemoglobin <9.0 g/dL (transfusions and/or erythropoietin were
permitted);

- absolute neutrophil count (ANC) <=1.5 x 10^9/L;

- platelet count <100 x 10^9/L;

- total bilirubin >1.25 x upper limit of normal (ULN) for institution,

- aspartate transaminase/glutamic oxaloacetic transaminase (AST/SGOT) and alanine
transaminase/ glutamic pyruvic transaminase (ALT/SGPT) >2.0 x ULN, serum
creatinine >2.0 x ULN for age and sex;

- Coexistent second malignancy or history of prior malignancy within previous 5 years
(excluding basal or squamous cell carcinoma of the skin or cervical epithelial
neoplasm [CIN1, carcinoma in situ] that had been treated curatively).

- Any significant medical or psychiatric condition that might have prevented the
patient from complying with all study procedures.

- Patients who were pregnant or breast-feeding. All women of child bearing potential
were to use an effective method of contraception (either an intrauterine device or a
double barrier method using condoms or a diaphragm plus spermicide) during the study
and for at least one month after receiving the last dose of romidepsin. Male patients
were to use a barrier method of contraception (condoms) during the treatment period
and for at least 1 month thereafter. Hormonal methods of contraception such as the
contraceptive pill or patch (particularly those containing ethinyl estradiol) were to
be avoided due to a potential drug interaction.

- Use of topical steroids in the previous 2 weeks or systemic steroids in the previous
4 weeks.

- Having previously given consent to participate in this study.

- Concomitant use of CYP3A4 inhibitors.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

The Percent of Patients (Pts) With Objective Disease Response

Outcome Description:

The percent of pts with confirmed Objective Disease Response (confirmed best responses of complete response [CR], clinical complete response [CCR], or partial response [PR]). Responses were evaluated according to a composite assessment (Objective Primary Disease Response Evaluation Criteria - OPDREC).

Outcome Time Frame:

6 months

Safety Issue:

No

Principal Investigator

Jean Nichols, Ph.D.

Investigator Role:

Study Director

Investigator Affiliation:

Gloucester Pharmaceuticals, Inc.

Authority:

United States: Food and Drug Administration

Study ID:

GPI-04-0001

NCT ID:

NCT00106431

Start Date:

January 2005

Completion Date:

December 2008

Related Keywords:

  • Cutaneous T-cell Lymphoma
  • romidepsin
  • Lymphoma
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous

Name

Location

MD Anderson Cancer CenterHouston, Texas  77030-4096
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Boston Medical CenterBoston, Massachusetts  02118
UCLA Jonsson Cancer CenterLos Angeles, California  90095
Stanford Comprehensive Cancer CenterStanford, California  94305
University of Pennsylvania Abrahamson Cancer CenterPhiladelphia, Pennsylvania  19104