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

NCT00106431 | Completed Phase 2 Results DMC

• 1 other identifier: GPI-04-0001
• Study Type: interventional
• Target: 102
• Locations: 6 countries
• Sites: 11

Brief Summary

GPI-04-0001 was a Phase II, non-randomized, open label, single arm study that was conducted at approximately 30 sites, primarily in the United States, Europe and Russia. It assessed the efficacy, safety, and tolerability of romidepsin as a treatment for cutaneous T-cell lymphoma (CTCL). Study patients (pts) received romidepsin in a dose of 14 mg/m\^2 intravenously over 4 hours on Days 1, 8 and 15 of each 28-day cycle. The duration of study treatment was 6 cycles although pts who showed an objective response or stable disease could continue to receive therapy, at the discretion of the investigator, until disease progression or another withdrawal criterion was met.

Conditions

Cutaneous T-cell Lymphoma

Keywords

romidepsin

Outcome Measures

Primary Outcomes (1)

• The Percent of Patients (Pts) With Objective Disease Response

  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).

  6 months

Secondary Outcomes (6)

• Duration of Objective Disease Response

  Up to 10 months; median duration of follow up was 5.1 months

• Time to Objective Disease Response

  Up to 10 months

• Time to Disease Progression

  Up to 10 months; median duration of follow up was 6.1 months

• Decrease in Pruritus Visual Analogue Scale (VAS) Score of ≥30 mm or a Score of 0 for at Least 2 Consecutive Cycles.

  Up to 10 months

• Duration of Objective Disease Control (ODC)

  Up to 10 months; median duration of follow up was 6.0 months

Interventions

romidepsin (depsipeptide, FK228) DRUG

Study patients received romidepsin at a dose of 14 mg/m\^2 intravenously over 4 hours on Days 1, 8 and 15 of each 28-day cycle. The duration of study treatment was 6 cycles although patients who showed an objective response or stable disease could continue to receive therapy, at the discretion of the investigator, until disease progression or another withdrawal criterion was met.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celgene: lead
• Celgene Corporation: collaborator

Study Sites (11)

UCLA Jonsson Cancer Center

Los Angeles, California, 90095, United States

Location

Stanford Comprehensive Cancer Center

Stanford, California, 94305, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

University of Pennsylvania Abrahamson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Research Site

Multiple Locations, France

Location

Research Site

Multiple Locations, Germany

Location

Research Site

Multiple Locations, Poland

Location

Research Site

Multiple Locations, Russia

Location

Research Site

Multiple Locations, United Kingdom

Location

Related Publications (7)

• Duvic M, Bates SE, Piekarz R, Eisch R, Kim YH, Lerner A, Robak T, Samtsov A, Becker JC, McCulloch W, Waksman J, Whittaker S. Responses to romidepsin in patients with cutaneous T-cell lymphoma and prior treatment with systemic chemotherapy. Leuk Lymphoma. 2018 Apr;59(4):880-887. doi: 10.1080/10428194.2017.1361022. Epub 2017 Aug 30.

  PMID: 28853310 BACKGROUND

• Foss F, Duvic M, Lerner A, Waksman J, Whittaker S. Clinical Efficacy of Romidepsin in Tumor Stage and Folliculotropic Mycosis Fungoides. Clin Lymphoma Myeloma Leuk. 2016 Nov;16(11):637-643. doi: 10.1016/j.clml.2016.08.009. Epub 2016 Aug 10.

  PMID: 27637428 BACKGROUND

• Foss F, Coiffier B, Horwitz S, Pro B, Prince HM, Sokol L, Greenwood M, Lerner A, Caballero D, Baran E, Kim E, Nichols J, Balser B, Wolfson J, Whittaker S. Tolerability to romidepsin in patients with relapsed/refractory T-cell lymphoma. Biomark Res. 2014 Sep 8;2:16. doi: 10.1186/2050-7771-2-16. eCollection 2014.

  PMID: 25279222 BACKGROUND

• Demierre M, et al. Pooled analyses of two international, multicenter clinical studies of romidepsin in 167 patients with cutaneous T-cell lymphoma (CTCL). Presented at 2009 ASCO Annual Meeting, May 29-June 2, 2009, Orlando, FL. Abstract No: 8546. J Clin Oncol 27:15s, 2009 (suppl)

  BACKGROUND

• Cabell C, et al. Systematic Assessment of Potential Cardiac Effects of the Novel Histone Deacetylase (HDAC) Inhibitor Romidepsin. Presented at 2009 ASCO Annual Meeting, May 29-June 2, 2009, Orlando, FL. Abstract No: e19533. C J Clin Oncol 2009;27(suppl)

  BACKGROUND

• Kim YH, et al. Clinically Significant Responses Achieved with Romidepsin in 37 Patient with Cutaneous T-Cell Lymphoma (CTCL) with Blood Involvement. Presented at American Society of Hematology 2009, New Orleans, LA. Abstract No. 2683.

  BACKGROUND

• Whittaker SJ, Demierre MF, Kim EJ, Rook AH, Lerner A, Duvic M, Scarisbrick J, Reddy S, Robak T, Becker JC, Samtsov A, McCulloch W, Kim YH. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. J Clin Oncol. 2010 Oct 10;28(29):4485-91. doi: 10.1200/JCO.2010.28.9066. Epub 2010 Aug 9.

  PMID: 20697094 RESULT

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous

Interventions

romidepsin; Depsipeptides

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Elizabeth Faust, PhD, Vice President, Clinical Research Services
• Organization: Celgene Corporation

EFaust@Celgene.com

617/583-1300

Study Officials

• Jean Nichols, Ph.D.

  Gloucester Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2005
• First Posted: March 25, 2005
• Study Start: January 1, 2005
• Primary Completion: June 1, 2008
• Study Completion: December 1, 2008
• Last Updated: October 30, 2019
• Results First Posted: April 23, 2010

Record last verified: 2019-10

Locations

DE (1); US (6); PL (1); GB (1); FR (1); RU (1)