Bexarotene + Radiotherapy for Cutaneous T-Cell Lymphoma

Overseen By Shamir Geller

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Oral retinoids, Gemfibrozil

Disqualifiers: Anaplastic large cell lymphoma, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 82 days

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the safety of combining bexarotene, a vitamin A derivative, with TSEB radiotherapy in patients with mycosis fungoides, a type of skin lymphoma. Bexarotene helps stop and kill cancer cells, while TSEB radiotherapy uses low-dose radiation to treat the skin. Researchers believe this combination may be more effective than using each treatment separately. Bexarotene has been used for both early and advanced cutaneous T-cell lymphoma (CTCL).

Do I need to stop my current medications to join the trial?

The trial does not specify that you must stop all current medications, but you cannot take oral retinoid therapy within 3 weeks of starting the study drug. Gemfibrozil is prohibited, and you should avoid strong/moderate CYP3A4 inducers and inhibitors if possible. Systemic steroids are not allowed within two weeks of the first dose, unless approved by the investigator.

Do I need to stop my current medications for this trial?

You may need to stop certain medications before joining the trial. Specifically, you cannot take oral retinoid therapy within 3 weeks of starting the study drug, and you should avoid gemfibrozil and certain other medications that interact with bexarotene. It's best to discuss your current medications with the study team to see if any changes are needed.

What data supports the idea that Bexarotene + Radiotherapy for Cutaneous T-Cell Lymphoma is an effective treatment?

The available research shows that Bexarotene, when used alone, has been effective in treating Cutaneous T-Cell Lymphoma. In one study, 71% of patients who took Bexarotene capsules experienced a positive response, with improvements starting in about 27 days and lasting for an average of 92 days. Another study found that Bexarotene had a response rate of over 50% in patients who did not respond to other treatments. These results suggest that Bexarotene is effective on its own, and it is considered a good candidate for combination with other treatments like radiotherapy. However, the specific combination of Bexarotene and radiotherapy was not directly studied in the available research. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Bexarotene for treating cutaneous T-cell lymphoma?

Research shows that Bexarotene has been effective in treating cutaneous T-cell lymphoma, with more than 50% of patients responding positively, even those who did not respond to previous treatments. In one study, 71% of patients achieved a partial response, indicating that Bexarotene can be a beneficial option for this condition. ^{1 2 3 4 5}

What safety data is available for Bexarotene treatment in cutaneous T-cell lymphoma?

Bexarotene, also known as Targretin, has been studied for its safety in treating cutaneous T-cell lymphoma. Adverse events associated with its use include bleeding, hemorrhage, coagulopathy, hypertriglyceridemia, central hypothyroidism, and xeroderma. These side effects can often be managed with dose adjustments or additional medications. Bexarotene is generally well-tolerated and has shown efficacy in clinical trials, with a response rate greater than 50% in patients who were refractory or intolerant to previous therapies. It is considered a good candidate for combination therapy due to its minimal bone marrow toxicity. ^{1 2 3 4 6}

Is the combination of Bexarotene and Radiotherapy safe for treating Cutaneous T-Cell Lymphoma?

Bexarotene, used for treating Cutaneous T-Cell Lymphoma, can cause side effects like bleeding, high triglycerides (a type of fat in the blood), and thyroid issues. These side effects can often be managed with medication adjustments or additional treatments. ^{1 2 3 4 6}

Is the drug Bexarotene a promising treatment for cutaneous T-cell lymphoma?

Yes, Bexarotene is a promising drug for treating cutaneous T-cell lymphoma. It has shown a good response rate in patients who did not respond to previous treatments. It is generally well-tolerated and can be used in combination with other therapies, making it a flexible option for treatment. ^{1 2 3 4 7}

What makes the drug Bexarotene unique for treating cutaneous T-cell lymphoma?

Bexarotene is a unique drug for cutaneous T-cell lymphoma because it is a synthetic retinoid that specifically targets retinoid X receptors, offering a novel mechanism of action compared to other treatments. It is effective in patients who have not responded to previous therapies and can be used in combination with other treatments due to its low bone marrow toxicity. ^{1 2 3 4 7}

Research Team

Brandon Imber, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with a skin lymphoma called mycosis fungoides (MF) can join this trial. They should be in relatively good health, able to consent, and have an ECOG performance status of 0-2. Participants must not be pregnant, use two forms of contraception if applicable, and cannot have had certain other treatments or conditions that would interfere with the study.

Inclusion Criteria

I am 18 years old or older.

Baseline mSWAT score of at least 10

My skin cancer is at least stage IB or I have Sézary syndrome, and I haven't had systemic treatments or they didn't work.

Exclusion Criteria

Pregnancy

High likelihood of protocol non-compliance (in opinion of investigator)

I have been diagnosed with ALCL or another type of non-Hodgkin lymphoma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bexarotene and TSEB radiotherapy. Bexarotene starts at 150 mg daily on Day 1, increasing to 300 mg daily on Day 15. TSEB starts on Day 22 with safety assessment on Day 52.

82 days

Multiple visits for treatment and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of radiation dermatitis and skin response.

1 month

Treatment Details

Interventions

• Bexarotene
• Total Skin Electron Beam (TSEB)

Trial Overview The trial is testing the safety and effectiveness of combining bexarotene (a vitamin A-like drug) with TSEB radiotherapy—a type of radiation treatment for the skin—in treating MF. The goal is to see if using both treatments together works better than using them separately.

Participant Groups

Group I: Bexarotene Combined With Radiotherapy Experimental Treatment 2 Interventions

Patients will be initiated on bexarotene 150 mg daily on Day 1, with dose increase to 300 mg daily on Day 15. Patients will receive Cycle 1 of TSEB on Day 22 (with 2 Gy given on two consecutive days -Day 22 and 23), with safety assessment on Day 52. Efficacy will first be assessed on Day 52 and then again on Day 82 by global response assessment, including mSWAT. Patients who have less than 70% reduction from baseline mSWAT score will be eligible for subsequent cycles of TSEB (administered as 4 Gy over 2 consecutive days), until mSWAT score reduction of ≥ 70%, and up to a total of 6 cycles. Treatment may continue until disease progression, unacceptable toxicity, recommended termination by treating physician, or termination of the study.

Bexarotene is already approved in United States, European Union for the following indications:

Approved in United States as Targretin for:

• Cutaneous T-cell lymphoma

Approved in European Union as Targretin for:

• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

Bexarotene, an antitumoral agent for cutaneous T-cell lymphoma, has been shown to increase clotting times in both in vitro and in vivo studies, indicating its anticoagulant effects.

The drug primarily inhibits factor IX and factor X without significantly affecting other coagulation factors, suggesting that patients on bexarotene should be monitored for coagulation issues, especially if they have existing deficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interactions of bexarotene (LGD1069, Targretin) with the coagulation system. Hespel, A., Mejdoubi-Charef, N., Yous, S., et al.[2018]

In a study involving eight patients with cutaneous T-cell lymphoma, bexarotene showed significant efficacy, with 71% of those taking the oral formulation achieving a partial response within an average of 27 days.

Bexarotene was generally well-tolerated, although the oral form caused hypertriglyceridemia in some patients; the topical gel showed long-lasting effects, with one patient maintaining a partial response for 31 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene capsules and gel for previously treated patients with cutaneous T-cell lymphoma: results of the Australian patients treated on phase II trials. Prince, HM., McCormack, C., Ryan, G., et al.[2019]

In a phase III study involving 50 patients with early-stage cutaneous T-cell lymphoma, topical bexarotene gel 1% showed substantial efficacy, with overall response rates of 44% to 54% depending on the assessment method used.

The treatment was generally well tolerated, with only mild to moderate side effects such as skin irritation and pruritus, and no serious treatment-related adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. Heald, P., Mehlmauer, M., Martin, AG., et al.[2019]

Bexarotene is an effective treatment for cutaneous T-cell lymphoma, showing over a 50% response rate in patients who did not respond to or could not tolerate previous therapies, based on Phase II/III trials.

While bexarotene can cause side effects like central hypothyroidism and elevated cholesterol, these can be managed, making it a strong candidate for combination therapies with other treatments for cutaneous T-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene: a clinical review. Farol, LT., Hymes, KB.[2018]

In a study of 66 patients with advanced cutaneous T-cell lymphoma (CTCL), bexarotene showed an overall response rate of 44%, with 9% achieving complete response and 35% achieving partial response, indicating its efficacy across different stages of the disease.

Bexarotene was well tolerated, with common side effects including central hypothyroidism and hyperlipidaemia, both of which were manageable, suggesting a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene therapy for mycosis fungoides and Sézary syndrome. Abbott, RA., Whittaker, SJ., Morris, SL., et al.[2018]

Bexarotene, an antitumoral agent, causes hypertriglyceridemia by activating the RXR/LXR heterodimer, which specifically influences lipogenic gene expression in the liver.

The study found that while bexarotene increases triglyceride levels, it does not affect cholesterol homeostasis, indicating a selective action on metabolic pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rexinoid bexarotene modulates triglyceride but not cholesterol metabolism via gene-specific permissivity of the RXR/LXR heterodimer in the liver. Lalloyer, F., Pedersen, TA., Gross, B., et al.[2021]

In a pilot trial involving 10 patients with advanced cutaneous T-cell lymphomas, bexarotene showed limited efficacy, achieving only short partial remissions in 2 patients and lasting stabilization in 4 patients, while 4 patients experienced disease progression.

Bexarotene treatment led to significant adverse effects, including hypertriglyceridemia in 6 patients, resulting in therapy suspension for 3 patients, indicating that the risks may outweigh the benefits for standard treatment use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene--an alternative therapy for progressive cutaneous T-cell lymphoma? First experiences. Bohmeyer, J., Stadler, R., Kremer, A., et al.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Interactions of bexarotene (LGD1069, Targretin) with the coagulation system. [2018]

2. Australia pubmed.ncbi.nlm.nih.gov

Bexarotene capsules and gel for previously treated patients with cutaneous T-cell lymphoma: results of the Australian patients treated on phase II trials. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Bexarotene: a clinical review. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Bexarotene therapy for mycosis fungoides and Sézary syndrome. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Rexinoid bexarotene modulates triglyceride but not cholesterol metabolism via gene-specific permissivity of the RXR/LXR heterodimer in the liver. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Bexarotene--an alternative therapy for progressive cutaneous T-cell lymphoma? First experiences. [2019]