Romidepsin for Cancer and Chronic Lymphocytic Leukemia with Liver Dysfunction

No longer recruiting at 11 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Thiazolidinediones, Warfarin, others

Disqualifiers: Prostate cancer, Neuroendocrine tumors, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 28 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects and optimal dose of romidepsin (Istodax) for individuals with cancer, including lymphoma, chronic lymphocytic leukemia, or solid tumors, who also have liver issues. Romidepsin halts cancer cell growth and survival, potentially slowing or stopping disease progression. It suits those whose cancer has not responded to standard treatments and who have liver dysfunction. Participants must have a life expectancy of over three months and stable liver function. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking research.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications at least 7 days before starting romidepsin. If you're on medications that affect the activity of romidepsin, your eligibility will be reviewed by the principal investigator. Some medications, especially those affecting the heart's rhythm, are not allowed.

Is there any evidence suggesting that romidepsin is likely to be safe for humans?

Research has shown that the FDA has approved romidepsin to treat cutaneous T-cell lymphoma (CTCL), confirming its safety for people with this condition. Studies have found that romidepsin is generally well-tolerated, though some patients may experience side effects. Common side effects include nausea, fatigue, and changes in blood cell counts, which are usually manageable.

This trial tests romidepsin on patients with liver problems, who might react differently. As an early phase trial, the main goal is to understand the side effects and determine the best dose for these patients. Researchers focus on safety and closely monitor participants for any adverse effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Romidepsin is unique because it works as a histone deacetylase (HDAC) inhibitor, a mechanism not commonly used in most current treatments for cancer and chronic lymphocytic leukemia (CLL), which typically include chemotherapy and monoclonal antibodies. Unlike these standard options, romidepsin targets the genetic material within cells, potentially reactivating tumor suppressor genes and inhibiting cancer cell growth. Researchers are excited about romidepsin because it offers a novel approach to treating patients with liver dysfunction, a group that often has limited treatment options due to the liver's role in processing most medications.

What evidence suggests that romidepsin might be an effective treatment for cancer and chronic lymphocytic leukemia with liver dysfunction?

Research has shown that romidepsin, which participants in this trial will receive, is effective for some blood cancers. The FDA has approved it for treating cutaneous T-cell lymphoma. In some individuals with chronic lymphocytic leukemia (CLL), romidepsin reduced cancer cells by more than 50%. However, it did not produce significant results in other blood cancers such as AML and MDS. Romidepsin blocks proteins that aid cancer cell growth and survival. ^{1 2 3 4 6}

Who Is on the Research Team?

Roisin Connolly, MD

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for patients with lymphoma, chronic lymphocytic leukemia, or solid tumors who also have liver dysfunction. They must be relatively active (able to care for themselves), not have had certain cancers that didn't respond to previous phase 2 studies unless they are in moderate/severe liver dysfunction groups, and meet specific health criteria including blood counts and kidney function. Pregnant women and those with significant heart disease or on certain medications like warfarin cannot join.

Inclusion Criteria

I have previously been treated with romidepsin.

You need to have a certain level of red blood cells, white blood cells, platelets, and a substance called creatinine in your blood.

I have relapsed or refractory PTCL or CTCL without time restrictions on my last treatment.

Exclusion Criteria

I do not have prostate, renal cell, neuroendocrine, lung, colorectal cancers, soft tissue sarcomas, glioma, or thyroid cancer.

I haven't had major surgery or antibody therapies recently.

Patients may not be receiving any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive romidepsin intravenously over 4 hours on days 1, 8, and 15 of a 28-day cycle

28 days

3 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Romidepsin

Trial Overview The trial is testing the effects of a drug called Romidepsin on various types of cancer in patients with liver problems. It aims to find the safest dose that can manage cancer growth by blocking proteins essential for cancer cell survival.

How Is the Trial Designed?

Group I: Treatment (romidepsin) Experimental Treatment 2 Interventions

Patients receive romidepsin IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Istodax for:

• Cutaneous T-cell lymphoma (CTCL)
• Peripheral T-cell lymphoma (PTCL)

Approved in European Union as Istodax for:

• Cutaneous T-cell lymphoma (CTCL)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01638533

Romidepsin in Treating Patients With Lymphoma, Chronic ... This phase I trial studies the side effects and best dose of romidepsin in treating patients with lymphoma, chronic lymphocytic leukemia, or solid tumors ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7457146/

A focus on the preclinical development and clinical status ... Romidepsin has mainly been developed as a therapy for hematologic malignancies and is approved by the US FDA for the treatment of cutaneous T-cell lymphomas.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5136743/

Romidepsin Controls Chronic Lymphocytic Leukemia in a ... A phase I trial performed by Byrd et al. demonstrated that patients with CLL who were treated with romidepsin had on average over a 50% decrease in their ...

4. aetna.com aetna.com/cpb/medical/data/800_899/0865.html

Romidepsin - Medical Clinical Policy Bulletins Wang and associates (2017) stated that romidepsin (FK228) is one of the most promising HDAC inhibitors due to its potent anti-tumor activity, and has been used ...

5. sciencedirect.com sciencedirect.com/topics/agricultural-and-biological-sciences/romidepsin

Romidepsin - an overview In patients with chronic lymphocytic leukemia, AML, or MDS, romidepsin did not have significant clinical efficacy [46,47]. The drug did exhibit biological ...

6. news.bms.com news.bms.com/news/details/2021/Bristol-Myers-Squibb-Statement-on-Istodax-romidepsin-Relapsed-Refractory-Peripheral-T-cell-Lymphoma-U.S.-Indication/default.aspx

Bristol Myers Squibb Statement on Istodax® (romidepsin) ... Istodax (romidepsin) for injection is indicated for treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic ...