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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Targretin® (bexarotene)

pegylated liposomal doxorubicin hydrochloride

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Hackensack University Medical Center Cancer Center
Roswell Park Cancer Institute
NYU Cancer Institute at New York University Medical Center
Memorial Sloan Kettering Cancer Center
M. D. Anderson Cancer Center at University of Texas

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Doxil and Targretin® (bexarotene)

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

NCT ID

NCT00255801

First Posted

November 18, 2005

Last Updated

July 19, 2018

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI), Tibotec Pharmaceutical Limited, M.D. Anderson Cancer Center, NYU Langone Health, Hackensack Meridian Health, Roswell Park Cancer Institute

1. Study Identification

Unique Protocol Identification Number

NCT00255801

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

November 2005 (undefined)

Primary Completion Date

October 2017 (Actual)

Study Completion Date

October 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI), Tibotec Pharmaceutical Limited, M.D. Anderson Cancer Center, NYU Langone Health, Hackensack Meridian Health, Roswell Park Cancer Institute

4. Oversight

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

37 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Doxil and Targretin® (bexarotene)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Targretin® (bexarotene)

Intervention Type

Drug

Intervention Name(s)

pegylated liposomal doxorubicin hydrochloride

Primary Outcome Measure Information:

Title

Median Progression-free Survival

Description

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

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Maximum Therapeutic Response

Description

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

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David J. Straus, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Steven M. Horwitz, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Patricia L. Myskowski, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hackensack University Medical Center Cancer Center

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

Facility Name

Roswell Park Cancer Institute

City

Buffalo

State/Province

New York

ZIP/Postal Code

14263-0001

Country

United States

Facility Name

NYU Cancer Institute at New York University Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

M. D. Anderson Cancer Center at University of Texas

City

Houston

State/Province

Texas

ZIP/Postal Code

77030-4009

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24285015

Citation

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.

Results Reference

derived

Links:

URL

http://www.mskcc.org/

Description

Memorial Sloan Kettering Cancer Center

Lymphoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial