Everolimus in Treating Cutaneous T-cell Lymphoma (CTCL)

November 25, 2016 updated by: Adam Lerner

PHASE II TRIAL OF THE mTOR INHIBITOR EVEROLIMUS IN RELAPSED OR REFRACTORY CUTANEOUS T-CELL LYMPHOMA (CTCL)

CTCL is a rare form of lymphoma of the skin. While early stages are usually confined to the skin, later stages may spread to blood, lymph nodes and other organs. At this point, patients usually require systemic chemo. This study will investigate the effect of everolimus as treatment for recurrent or refractory CTCL. Participation in this study will last as long as the study doctor believes disease has not gotten worse, and patients continue to tolerate the study medication for a maximum of 1 year. Once off the treatment, patients will be followed for two years.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Cutaneous T-cell lymphoma is a rare form of lymphoma of the skin. While early stages are usually confined to the skin, later stages may spread to blood, lymph nodes and other organs. At this point, patients usually require systemic chemotherapy. This study will investigate the effect of everolimus as a treatment for patients diagnosed with CTCL that has either not responded to previous treatments or has recurred despite previous treatments. Everolimus is the common name for the commercial drug Afinitor® (Novartis). It is approved by the U.S. Food and Drug Administration (FDA) for use in kidney and brain cancer. In several different forms of lymphomas, everolimus is used as an investigational drug, which means it has not been approved by the FDA for this group of diseases.

Everolimus blocks a protein (mTOR) that helps cells and tumors to grow. Earlier studies have indicated that the drug everolimus may work against lymphomas including cutaneous T-cell lymphomas. Participation in this study will last as long as the study doctor believes disease has not gotten worse, and patients continue to tolerate the study medication for a maximum of 1 year. Once off the treatment, patients will be followed for two years.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Clinically and histologically confirmed diagnosis of CTCL (at least stage IB for mycosis fungoides and Sézary syndrome, and T2 and/or refractory to at least one prior treatment for CTCL other than mycosis fungoides/Sézary syndrome)
  • Relapsed or refractory disease after at least one standard systemic treatment including extracorporeal photopheresis (ECP), oral bexarotene, interferon, HDAC inhibitors
  • ≥18 years old
  • WHO performance status ≤ 2
  • Life expectancy ≥ 6 months
  • ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb >9 g/dL
  • Serum bilirubin ≤ 1.5 x ULN
  • ALT and AST ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases)
  • INR ≤1.5 (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for >2 weeks at time of randomization)
  • Serum creatinine ≤ 1.5 x ULN
  • Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L
  • Fasting triglycerides ≤ 2.5 x ULN.

Exclusion Criteria:

  • Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of stating study drug
  • Treatment with any investigational drug within the past 4 weeks
  • Patients, who have had major surgery or significant traumatic injury within 4 weeks of starting study drug, patients who have not recovered from the side effects of any major surgery, or patients that may require major surgery during the study
  • Patients receiving chronic, systemic treatment with corticosteroids or any immunosuppressive agent other than topical or inhaled corticosteroids
  • Patients receiving immunization with attenuated live vaccines within one week of study entry or during study period
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
  • Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
  • Symptomatic congestive heart failure of New York heart Association Class III or IV
  • unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
  • severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air
  • uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN (Note: Optimal glycemic control should be achieved before starting trial therapy.)
  • active (acute or chronic) or uncontrolled severe infections
  • liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
  • A known history of HIV seropositivity
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus
  • Patients with an active, bleeding diathesis
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Adequate contraception must be used throughout the trial and for 8 weeks after the last dose of study drug, by both sexes.
  • Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
  • Patients who have received prior treatment with an mTOR inhibitor
  • Patients with a known hypersensitivity to everolimus or other rapamycins or to its excipient
  • History of noncompliance to medical regimens
  • Patients unwilling to or unable to comply with the protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: all patients on study

This will be a prospective, phase II non-randomized, open label study of single agent everolimus for the treatment of CTCL recurrent or refractory to at least one previous treatment other than topical medication. The purpose will be evaluation of safety and anti-tumor response as evaluated by serial skin examinations and assessment of tumor burden in tissue and blood.

This study will be conducted in 2 stages. During stage 1 we will enroll a maximum of 11 subjects to evaluate response rate and will only continue to stage 2, if we observe two or more responses. During stage 2, we will expand the study to an overall N of 28 patients.
Drug: Everolimus

The study drug everolimus will be self-administered (by the patients themselves). The investigator will instruct the patient to take the study drug exactly as specified in the protocol. Everolimus should be administered orally once daily, preferably in the morning, at the same time every day with our without food. Everolimus tablets should be swallowed whole with a glass of water. The tablets must not be chewed or crushed.

Everolimus will be administered orally as once daily dose of 10 mg continuously from study day 1 until progression of disease or unacceptable toxicity.

If vomiting occurs, no attempt should be made to replace the vomited dose. All dosages prescribed and dispensed to the patient and all dose changes during the study must be recorded.

Other Names:
  • Afinitor

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Efficacy of Treatment
Time Frame: 12 months after beginning treatment
Determine the efficacy of everolimus in the treatment of CTCL as overall response rate (ORR)
12 months after beginning treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to Response
Time Frame: three months
Determine time to response (TTR)/duration of objective response (DOR)
three months
Progression-free Survival
Time Frame: two years after discontinuing study treatment
Determine progression-free survival of CTCL patients treated with everolimus
two years after discontinuing study treatment
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time Frame: Up to one year
Determine the adverse event profile and tolerability of everolimus in patients with CTCL
Up to one year
Effect of mTOR on Tumors
Time Frame: one year
Determine mTOR (mammilian target of rapamycin) pathway activation and number of regulatory T cells (Tregs) in pre-treated tumor tissue and evaluate changes following treatment
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Adam Lerner

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novartis

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Adam Lerner, MD, Boston University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 2, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 6, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 10, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 12, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 25, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • H-30213

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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