Everolimus in Treating Cutaneous T-cell Lymphoma

Phase 2

Terminated

Conditions: Cutaneous T-Cell Lymphoma

Interventions: Drug: Everolimus

Registration Number: NCT01637090

Lead Sponsor: Adam Lerner

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
all patients on study	Everolimus	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.

Primary Outcome Measures

Name	Time	Method
Efficacy of Treatment	12 months after beginning treatment	Determine the efficacy of everolimus in the treatment of CTCL as overall response rate (ORR)

Secondary Outcome Measures

Name	Time	Method
Time to Response	three months	Determine time to response (TTR)/duration of objective response (DOR)
Progression-free Survival	two years after discontinuing study treatment	Determine progression-free survival of CTCL patients treated with everolimus
Effect of mTOR on Tumors	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
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	Up to one year	Determine the adverse event profile and tolerability of everolimus in patients with CTCL