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

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00255801
• Collaborator: National Cancer Institute (NCI) (NIH), Tibotec Pharmaceutical Limited (Industry), M.D. Anderson Cancer Center (Other), NYU Langone Health (Other), Hackensack Meridian Health (Other), Roswell Park Cancer Institute (Other)
• Enrollment: 37
• Locations: 5
• Arm: 1
• Duration (Months): 143
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: Targretin® (bexarotene); Drug: pegylated liposomal doxorubicin hydrochloride	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Doxorubicin HCl Liposome Injection (Doxil®) in Advanced Stage Cutaneous T-Cell Lymphoma Followed by Bexarotene (Targretin®)
• Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: Oct 1, 2017
• Actual Study Completion Date: Oct 1, 2017

Arms and Interventions

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: Targretin® (bexarotene); Drug: pegylated liposomal doxorubicin hydrochloride

Outcome Measures

Primary Outcome Measures

1. Median Progression-free Survival [3 years]

   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

1. Maximum Therapeutic Response [2 years]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey	United States	07601
2	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
3	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
4	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
5	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009

Sponsors and Collaborators

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

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 9, 2008

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00255801
• Other Study ID Numbers: 05-098; MSKCC-05098
• First Posted: Nov 21, 2005
• Last Update Posted: Aug 16, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Memorial Sloan Kettering Cancer Center: 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
• Additional relevant MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous; Doxorubicin; Liposomal doxorubicin; Bexarotene

Study Results

Participant Flow

Arm/Group Title	Doxil and Targretin® (Bexarotene)
Arm/Group 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.
Period Title: Overall Study
STARTED	37
COMPLETED	37
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Doxil and Targretin® (Bexarotene)
Arm/Group 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.
Overall Participants	37
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56
Sex: Female, Male (Count of Participants)
Female	17 45.9%
Male	20 54.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 18.9%
Not Hispanic or Latino	30 81.1%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 2.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	13 35.1%
White	22 59.5%
More than one race	0 0%
Unknown or Not Reported	1 2.7%
Region of Enrollment (Count of Participants)
United States	37 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Doxil and Targretin® (Bexarotene)
Arm/Group 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.
Measure Participants	37
Median (Full Range) [months]	5

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Doxil and Targretin® (Bexarotene)
Arm/Group 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.
Measure Participants	37
Clinical Complete Response	2 5.4%
Partial Response	12 32.4%
Stable Disease	6 16.2%
Progressive Disease	14 37.8%
Not Evaluable	3 8.1%

Adverse Events

Time Frame	2 years
Arm/Group Title	Doxil and Targretin® (Bexarotene)
Arm/Group 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.
All Cause Mortality
	Doxil and Targretin® (Bexarotene)
	Affected / at Risk (%)	# Events
Total	12/37 (32.4%)
Serious Adverse Events
	Doxil and Targretin® (Bexarotene)
	Affected / at Risk (%)	# Events
Total	15/37 (40.5%)
Cardiac disorders
Cardiac Arrhythmia, other	1/37 (2.7%)
Gastrointestinal disorders
Gastritis (incl bile reflux gastritis)	1/37 (2.7%)
General disorders
Death not assoc w CTCAE term-Disease prog NOS	1/37 (2.7%)
Fever (in the absence of neutropenia)	1/37 (2.7%)
Rigors/chills	2/37 (5.4%)
Infections and infestations
Inf norm ANC/gr1/2 neut-Cellulitis(skin)	1/37 (2.7%)
Inf unknown ANC-Blood	1/37 (2.7%)
Inf unknown ANC-Cellulitis(skin)	1/37 (2.7%)
Infection, other	5/37 (13.5%)
Injury, poisoning and procedural complications
Fracture	1/37 (2.7%)
Investigations
Leukocytes (total WBC)	1/37 (2.7%)
Neutrophils/granulocytes (ANC/AGC)	1/37 (2.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain - Tumor pain	1/37 (2.7%)
Respiratory, thoracic and mediastinal disorders
Cough	1/37 (2.7%)
Pneumonitis/pulm infiltrates	1/37 (2.7%)
Skin and subcutaneous tissue disorders
Pain - Skin	1/37 (2.7%)
Pruritus/itching	1/37 (2.7%)
Ulceration	1/37 (2.7%)
Other (Not Including Serious) Adverse Events
	Doxil and Targretin® (Bexarotene)
	Affected / at Risk (%)	# Events
Total	37/37 (100%)
General disorders
Fatigue	4/37 (10.8%)
Investigations
White blood cells	9/37 (24.3%)
Cholesterol, high	7/37 (18.9%)
Neutrophils	4/37 (10.8%)
Lymphopenia	3/37 (8.1%)
Metabolism and nutrition disorders
Hyperglycemia	11/37 (29.7%)
Triglyceride, high	7/37 (18.9%)
Musculoskeletal and connective tissue disorders
Pain - Back	2/37 (5.4%)
Skin and subcutaneous tissue disorders
Pruritus/itching	3/37 (8.1%)
Rash: hand-foot skin reaction	2/37 (5.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.