Liposomal Doxorubicin in Treating Patients With Stage IIB, Stage IVA, or Stage IVB Recurrent or Refractory Mycosis Fungoides

Phase II Clinical Trial With Caelyx Mono-Chemotherapy in Patients With Advanced Mycosis Fungoides Stage IIb, IVa and IVb With or Without Previous Chemotherapy

RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin, use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of liposomal doxorubicin in treating patients who have stage IIB, stage IVA, or stage IVB recurrent or refractory mycosis fungoides.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: pegylated liposomal doxorubicin hydrochloride

Detailed Description

OBJECTIVES:

Primary

• Determine the antitumor activity of doxorubicin HCl liposome, in terms of response rate (complete response and partial response), in patients with stage IIB, IVA, or IVB recurrent or refractory mycosis fungoides.

Secondary

• Determine the time to progression and duration of response in patients treated with this drug.
• Determine the toxicity of this drug in these patients.

OUTLINE: This is an open-label, nonrandomized, multicenter study.

Patients receive doxorubicin HCl liposome IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity or until a maximum cumulative anthracycline(s) dose of 400 mg/m^2 has been reached (including anthracyclines from prior treatment).

Patients are followed every 12 weeks until disease progression.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study within 1 year.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, A-8010
    • Karl-Franzens-University Graz
  • Vienna, Austria, A-1090
    • Allgemeines Krankenhaus - Universitatskliniken
• Germany
  • Essen, Germany, D-45122
    • Universitaetsklinikum Essen
  • Jena, Germany, D-07740
    • Klinikum der Friedrich-Schiller Universitaet Jena
  • Mannheim, Germany, D-68135
    • Klinikum der Stadt Mannheim
  • Minden, Germany, D-32423
    • Klinikum Minden
  • Wuerzburg, Germany, D-97080
    • Julius Maximilians Universitaet Hospital
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
• Italy
  • Turin, Italy, 10126
    • Università di Torino
• Switzerland
  • Zurich, Switzerland, CH-8091
    • Universitaetsspital Zuerich
• United Kingdom
  • England
    • London, England, United Kingdom, SE1 9RT
      • St. Thomas' Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 116 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed mycosis fungoides

  • Stage IIB, IVA, or IVB

• Refractory or recurrent disease after at least 2 of the following prior therapies:

  • Local and/or systemic steroids
  • Retinoids
  • Interferon alfa
  • Local carmustine
  • Systemic chemotherapy
  • Psoralen and ultraviolet A (PUVA) light therapy
• No CNS involvement
• No erythroderma (T4)

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count at least 1,500/mm^3
• WBC at least 2,000/mm^3
• Platelet count at least 75,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT and SGPT no greater than 2.5 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• LVEF normal by echocardiography or radionuclide angiocardiography

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 2 years after study participation
• No psychological, familial, sociological, or geographical condition that would preclude study compliance or follow-up
• No active infection requiring specific therapy (e.g., antibiotics or anti-HIV therapy)
• No other prior or concurrent primary malignant tumor except adequately treated carcinoma in situ of the cervix or squamous cell or basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• More than 2 weeks since prior immunotherapy

Chemotherapy

• See Disease Characteristics

• Prior systemic chemotherapy allowed provided all of the following conditions are met:

  • Cumulative anthracycline dose is less than 200 mg/m^2
  • No allergy to anthracyclines
  • Prior methotrexate is low dose (i.e., weekly dose less than 30 mg)
• More than 2 weeks since prior chemotherapy

Endocrine therapy

• See Disease Characteristics
• No concurrent systemic steroids

Radiotherapy

• More than 2 weeks since prior radiotherapy

Surgery

• Not specified

Other

• Recovered from toxic effects of prior therapy, excluding alopecia
• No other concurrent anticancer therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Caelyx; doxorubicin HCl liposome IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses.	Drug: pegylated liposomal doxorubicin hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response (complete clinical [CCR] and partial resp. [PR]) rate by Tumor Burden Index for cutaneous disease and appearance or disappearance of lesions for noncutaneous disease every 8 wks during treatment and then every 12 wks until progression

Secondary Outcome Measures

Outcome Measure
Time to progression measured by Tumor Burden Index for cutaneous disease and appearance or disappearance of lesions for noncutaneous disease every 8 weeks during treatment
Duration of response measured by Tumor Burden Index for cutaneous disease and appearance or disappearance of lesions for noncutaneous disease every 8 weeks during treatment and then every 12 weeks until progression
Toxicity assessed by CTC v.2.0 at the end of each course

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Study Chair: Reinhard Dummer, MD, Universitaetsspital Zuerich

Publications and helpful links

General Publications

• Dummer R, Quaglino P, Becker JC, Hasan B, Karrasch M, Whittaker S, Morris S, Weichenthal M, Stadler R, Bagot M, Cozzio A, Bernengo MG, Knobler R. Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012. J Clin Oncol. 2012 Nov 20;30(33):4091-7. doi: 10.1200/JCO.2011.39.8065. Epub 2012 Oct 8.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: December 10, 2003
• First Submitted That Met QC Criteria: December 10, 2003
• First Posted (Estimate): December 11, 2003

Study Record Updates

• Last Update Posted (Actual): July 9, 2018
• Last Update Submitted That Met QC Criteria: July 6, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: stage IV cutaneous T-cell non-Hodgkin lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; stage IV mycosis fungoides/Sezary syndrome; recurrent mycosis fungoides/Sezary syndrome; stage II cutaneous T-cell non-Hodgkin lymphoma; stage II mycosis fungoides/Sezary syndrome
• Additional Relevant MeSH Terms: Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Bacterial Infections and Mycoses; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Lymphoma; Mycoses; Mycosis Fungoides; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: EORTC-21012; 2004-001746-32 (EudraCT Number)