Liposomal Doxorubicin Followed By Bexarotene in Treating Patients With Cutaneous T-Cell Lymphoma

Phase II Trial of Doxorubicin HCl Liposome Injection (Doxil®) in Advanced Stage Cutaneous T-Cell Lymphoma Followed by Bexarotene (Targretin®)

RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin and bexarotene, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bexarotene may also cause cutaneous T-cell lymphoma cells to look more like normal cells, and to grow and spread more slowly. Giving liposomal doxorubicin followed by bexarotene may be an effective treatment for cutaneous T-cell lymphoma.

PURPOSE: This phase II trial is studying how well giving liposomal doxorubicin followed by bexarotene works in treating patients with cutaneous T-cell lymphoma.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: pegylated liposomal doxorubicin hydrochloride; Drug: Targretin® (bexarotene)

Detailed Description

OBJECTIVES:

Primary

• Determine the progression-free survival of patients with stage IB-IV cutaneous T-cell lymphoma treated with doxorubicin HCl liposome followed by bexarotene.

Secondary

• Determine the complete and partial response rate in patients treated with this regimen.

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

Patients receive doxorubicin HCl liposome IV over 30-90 minutes once on day 1. Treatment repeats every 2 weeks for 8 courses. Beginning within 4 weeks after the last dose of doxorubicin HCl liposome, patients receive oral bexarotene once daily for at least 16 weeks. Patients who achieve a complete or partial response may continue to receive bexarotene in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center Cancer Center
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • NYU Cancer Institute at New York University Medical Center
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M. D. Anderson Cancer Center at University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed cutaneous T-cell lymphoma

  • Stage IB-IV disease
• Measurable disease

• Newly diagnosed or previously treated disease

  • No demonstrated resistance to prior bexarotene

PATIENT CHARACTERISTICS:

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin < 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• Ejection fraction ≥ 50% by MUGA or 2-D echocardiogram
• No New York Heart Association class II-IV heart disease
• No clinical evidence of congestive heart failure

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment
• No history of hypersensitivity reactions attributed to doxorubicin HCl liposome or its components
• No active potentially life-threatening infection
• No other acute disease

PRIOR CONCURRENT THERAPY:

Chemotherapy

• See Disease Characteristics
• Prior doxorubicin allowed provided the cumulative dose is ≤ 300 mg/m^2
• Prior epirubicin hydrochloride allowed provided the cumulative dose is ≤ 540 mg/m^2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Doxil and Targretin® (bexarotene); Patients will be treated with intravenous Doxil® every two weeks for 8 doses (16 weeks). Responses will be assessed. They will then receive Targretin® (bexarotene) orally for at least 16 weeks. Patients who achieve a CR or PR may continue on Targretin® (bexarotene) until relapse.	Drug: pegylated liposomal doxorubicin hydrochloride; Drug: Targretin® (bexarotene)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression-free Survival	CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT; CT scans of chest, abdomen and pelvis for TNM stage IV patients who had positive findings prior to treatment.; CBC with Sézary cell count and/or flow cytometry in patients with Sézary syndrome.; Dermatologic responses will be determined by the Severity-Weighted Assessment Tool (SWAT), a standardized approach to measuring the extent and severity of overall skin disease in patients with CTCL Primary skin tumor assessments were made by the modified Severity-Weighted Assessment Tool (mSWAT) [12, 13]; the Composite Assessment of Index Lesion Severity (CA) [9, 14] was used a secondary scale. Progression was defined as ≥25% increase in mSWAT skin score and ≥50% increase in the sum of the products of the greatest diameters of involved lymph nodes over baseline for patients with involved lymph nodes with stage IV disease	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Therapeutic Response	CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT; CT scans of chest, abdomen and pelvis for TNM stage IV patients who had positive findings prior to treatment.; CBC with Sézary cell count and/or flow cytometry in patients with Sézary syndrome.; Dermatologic responses will be determined by the Severity-Weighted Assessment Tool (SWAT), a standardized approach to measuring the extent and severity of overall skin disease in patients with CTCL Primary skin tumor assessments were made by the modified Severity-Weighted Assessment Tool (mSWAT) [12, 13]; the Composite Assessment of Index Lesion Severity (CA) [9, 14] was used a secondary scale. Progression was defined as ≥25% increase in mSWAT skin score and ≥50% increase in the sum of the products of the greatest diameters of involved lymph nodes over baseline for patients with involved lymph nodes with stage IV disease	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: M.D. Anderson Cancer Center; National Cancer Institute (NCI); NYU Langone Health; Roswell Park Cancer Institute; Hackensack Meridian Health; Tibotec Pharmaceutical Limited
• Investigators: Principal Investigator: David J. Straus, MD, Memorial Sloan Kettering Cancer Center; Principal Investigator: Steven M. Horwitz, MD, Memorial Sloan Kettering Cancer Center; Principal Investigator: Patricia L. Myskowski, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Straus DJ, Duvic M, Horwitz SM, Hymes K, Goy A, Hernandez-Ilizaliturri FJ, Feldman T, Wegner B, Myskowski PL. Final results of phase II trial of doxorubicin HCl liposome injection followed by bexarotene in advanced cutaneous T-cell lymphoma. Ann Oncol. 2014 Jan;25(1):206-10. doi: 10.1093/annonc/mdt480. Epub 2013 Nov 26.

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (ACTUAL): October 1, 2017
• Study Completion (ACTUAL): October 1, 2017

Study Registration Dates

• First Submitted: November 18, 2005
• First Submitted That Met QC Criteria: November 18, 2005
• First Posted (ESTIMATE): November 21, 2005

Study Record Updates

• Last Update Posted (ACTUAL): August 16, 2018
• Last Update Submitted That Met QC Criteria: July 19, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: stage I cutaneous T-cell non-Hodgkin lymphoma; stage I mycosis fungoides/Sezary syndrome; stage III cutaneous T-cell non-Hodgkin lymphoma; stage IV cutaneous T-cell non-Hodgkin lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; stage III mycosis fungoides/Sezary syndrome; 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: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin; Bexarotene
• Other Study ID Numbers: 05-098; MSKCC-05098