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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: Targretin® (bexarotene)
* Drug: pegylated liposomal doxorubicin hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Doxil and Targretin® (bexarotene)<br>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: Targretin® (bexarotene)<br> <br> Drug: pegylated liposomal doxorubicin hydrochloride<br> <br> |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome