Combination Drug Study of Bexarotene and Rosiglitazone to Treat CTCL

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Rosiglitazone and Bexarotene

About this trial

This is an interventional treatment trial for Cutaneous T-cell Lymphoma focused on measuring Cutaneous T-cell Lymphoma, CTCL, Mycosis Fungoides, Sezary Syndrome, Bexarotene, Targretin, Rosiglitazone, Avandia

Eligibility Criteria

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

Inclusion Criteria: Patients with biopsy proven persistent or recurrent cutaneous cell lymphoma (CTCL) Stage IA-IVA Patients with a pathologic proven diagnosis of CTCL that is documented in the patient history. Patient has preserved organ function. Patient has an ECOG performance status between 0 - 2. Women of childbearing potential should be screened for pregnancy prior to treatment and utilize effective contraceptive methods (e.g. barrier) during treatment period. Patients over the age of 18 who are willing and able to provide Informed Consent The patient has been taking Targretin capsules for at least the last 4 months and the dose has remained relatively stable. The patient has had stable or progressive disease over the past 4 months. Patient has adequate laboratory parameters for liver and kidney function. Exclusion Criteria: Patients with CD30+ Anaplastic Large Cell Lymphoma Patients with pathology consistent with peripheral T-cell lymphoma. Patients with Stage IVB (visceral involvement with CTCL). Patients with history of Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C infection. Patients with a diagnosis of congestive heart failure. Patients exhibiting significant edema or unstable cardiovascular disease. Patients with a fasting triglyceride level greater then 500mg/dl. Patients that have started any new treatment for CTCL in the past 4 months. Pregnant women will be excluded from the study.

Sites / Locations

Vanderbilt University Medical Center

Outcomes

Primary Outcome Measures

Number of Participants With a 50% Improvement in Baseline Skin Score

mSWAT scoring. Range 0 to 400. Measured every 4 weeks.

Secondary Outcome Measures

Quality of Life Evaluations

FACT-G, Functional Assessment of Cancer Therapy-General (quality-of-life scale) 0= worst 108=best

Pruritus Score

10-cm visual analog scale, 10= worst, 1=best

Full Information

NCT ID

NCT00178841

First Posted

September 12, 2005

Last Updated

January 20, 2016

Sponsor

Vanderbilt University

1. Study Identification

Unique Protocol Identification Number

NCT00178841

Brief Title

Combination Drug Study of Bexarotene and Rosiglitazone to Treat CTCL

Official Title

Open Label Pilot Study of Combination Therapy With Rosiglitazone and Bexarotene to Investigate a Possible Synergism in the Treatment of Cutaneous T-Cell Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

January 2016

Overall Recruitment Status

Completed

Study Start Date

June 2005 (undefined)

Primary Completion Date

March 2007 (Actual)

Study Completion Date

March 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vanderbilt University

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

The purpose of this trial is to determine if combination therapy with rosiglitazone and bexarotene might have a synergistic effect in the treatment of patients with CTCL.

Detailed Description

Treatment options for CTCL include both skin-directed and systemic therapies. Topical treatments are effective for early-stage disease that is localized to the skin. However, disease involving the lymph nodes or visceral sites can be palliated but rarely cured, even with the most aggressive regimens of systemic chemotherapy. Unfortunately, current treatment options at this stage only provide a short term response. Thus, it is important that additional therapies are investigated to manage this malignancy. Bexarotene has been approved by the FDA for the treatment of Cutaneous T-Cell Lymphoma (CTCL).Bexarotene binds the RXR(Retinoid X Receptor)inside the cell, a receptor that forms heterodimers with a multitude of other nuclear receptors. One of these is the PPARγ (Peroxisome Proliferator Activator Receptor Gamma), a nuclear receptor that binds Rosiglitazone.Rosiglitazone is an FDA approved antidiabetic agent of the Thiazolidinedione class. Rosiglitazone increases insulin sensitivity and is useful in the treatment of type 2 diabetes. In vitro data suggest that rosiglitazone and bexarotene may act synergistically to induce apoptosis in cell lines derived from patients with cutaneous T cell lymphoma (CTCL). This pilot study will investigate this possible synergism in a small cohort of patients with stable or progressive CTCL already being treated with bexarotene.

6. Conditions and Keywords

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

Cutaneous T-cell Lymphoma, Mycosis Fungoides, Sezary Syndrome

Keywords

Cutaneous T-cell Lymphoma, CTCL, Mycosis Fungoides, Sezary Syndrome, Bexarotene, Targretin, Rosiglitazone, Avandia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Rosiglitazone and Bexarotene

Intervention Description

rosiglitazone added to bexarotene capsules

Primary Outcome Measure Information:

Title

Number of Participants With a 50% Improvement in Baseline Skin Score

Description

mSWAT scoring. Range 0 to 400. Measured every 4 weeks.

Time Frame

16 weeks

Secondary Outcome Measure Information:

Title

Quality of Life Evaluations

Description

FACT-G, Functional Assessment of Cancer Therapy-General (quality-of-life scale) 0= worst 108=best

Time Frame

baseline and every 4 weeks

Title

Pruritus Score

Description

10-cm visual analog scale, 10= worst, 1=best

Time Frame

16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Patients with biopsy proven persistent or recurrent cutaneous cell lymphoma (CTCL) Stage IA-IVA Patients with a pathologic proven diagnosis of CTCL that is documented in the patient history. Patient has preserved organ function. Patient has an ECOG performance status between 0 - 2. Women of childbearing potential should be screened for pregnancy prior to treatment and utilize effective contraceptive methods (e.g. barrier) during treatment period. Patients over the age of 18 who are willing and able to provide Informed Consent The patient has been taking Targretin capsules for at least the last 4 months and the dose has remained relatively stable. The patient has had stable or progressive disease over the past 4 months. Patient has adequate laboratory parameters for liver and kidney function. Exclusion Criteria: Patients with CD30+ Anaplastic Large Cell Lymphoma Patients with pathology consistent with peripheral T-cell lymphoma. Patients with Stage IVB (visceral involvement with CTCL). Patients with history of Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C infection. Patients with a diagnosis of congestive heart failure. Patients exhibiting significant edema or unstable cardiovascular disease. Patients with a fasting triglyceride level greater then 500mg/dl. Patients that have started any new treatment for CTCL in the past 4 months. Pregnant women will be excluded from the study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John A Zic, MD

Organizational Affiliation

Vanderbilt University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232-5227

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

8085692

Citation

Bunn PA Jr, Hoffman SJ, Norris D, Golitz LE, Aeling JL. Systemic therapy of cutaneous T-cell lymphomas (mycosis fungoides and the Sezary syndrome). Ann Intern Med. 1994 Oct 15;121(8):592-602. doi: 10.7326/0003-4819-121-8-199410150-00007.

Results Reference

background

PubMed Identifier

8522490

Citation

Koh HK, Charif M, Weinstock MA. Epidemiology and clinical manifestations of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 1995 Oct;9(5):943-60.

Results Reference

background

PubMed Identifier

11331325

Citation

Duvic M, Hymes K, Heald P, Breneman D, Martin AG, Myskowski P, Crowley C, Yocum RC; Bexarotene Worldwide Study Group. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol. 2001 May 1;19(9):2456-71. doi: 10.1200/JCO.2001.19.9.2456.

Results Reference

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PubMed Identifier

15245439

Citation

Zhang C, Ni X, Konopleva M, Andreeff M, Duvic M. The novel synthetic oleanane triterpenoid CDDO (2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid) induces apoptosis in Mycosis fungoides/Sezary syndrome cells. J Invest Dermatol. 2004 Aug;123(2):380-7. doi: 10.1111/j.0022-202X.2004.23207.x.

Results Reference

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PubMed Identifier

14962523

Citation

Carr A, Workman C, Carey D, Rogers G, Martin A, Baker D, Wand H, Law M, Samaras K, Emery S, Cooper DA; Rosey investigators. No effect of rosiglitazone for treatment of HIV-1 lipoatrophy: randomised, double-blind, placebo-controlled trial. Lancet. 2004 Feb 7;363(9407):429-38. doi: 10.1016/S0140-6736(04)15489-5.

Results Reference

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PubMed Identifier

14759393

Citation

Wang TD, Chen WJ, Lin JW, Chen MF, Lee YT. Effects of rosiglitazone on endothelial function, C-reactive protein, and components of the metabolic syndrome in nondiabetic patients with the metabolic syndrome. Am J Cardiol. 2004 Feb 1;93(3):362-5. doi: 10.1016/j.amjcard.2003.10.022.

Results Reference

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PubMed Identifier

12502676

Citation

Raji A, Seely EW, Bekins SA, Williams GH, Simonson DC. Rosiglitazone improves insulin sensitivity and lowers blood pressure in hypertensive patients. Diabetes Care. 2003 Jan;26(1):172-8. doi: 10.2337/diacare.26.1.172.

Results Reference

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PubMed Identifier

15781673

Citation

Demierre MF, Tien A, Miller D. Health-related quality-of-life assessment in patients with cutaneous T-cell lymphoma. Arch Dermatol. 2005 Mar;141(3):325-30. doi: 10.1001/archderm.141.3.325.

Results Reference

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PubMed Identifier

445521

Citation

Bunn PA Jr, Lamberg SI. Report of the Committee on Staging and Classification of Cutaneous T-Cell Lymphomas. Cancer Treat Rep. 1979 Apr;63(4):725-8. No abstract available.

Results Reference

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PubMed Identifier

9207472

Citation

Willemze R, Kerl H, Sterry W, Berti E, Cerroni L, Chimenti S, Diaz-Perez JL, Geerts ML, Goos M, Knobler R, Ralfkiaer E, Santucci M, Smith N, Wechsler J, van Vloten WA, Meijer CJ. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood. 1997 Jul 1;90(1):354-71.

Results Reference

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PubMed Identifier

8718481

Citation

Shapiro PE. Advances in the histologic diagnosis of cutaneous T-cell lymphoma. Adv Dermatol. 1996;11:255-84; discussion 285. No abstract available.

Results Reference

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Links:

URL

http://www.ncbi.nlm.nih.gov/pubmed/17184879

Description

Pubmed link to article

Cutaneous T-cell Lymphoma, Mycosis Fungoides, Sezary Syndrome

About this trial

Eligibility Criteria

Sites / Locations

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