A Study for Participants With Relapsed Cutaneous T-Cell Lymphoma

Study Overview
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Brief Summary
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The purpose of the study is to determine the efficacy and safety of enzastaurin in participants with Cutaneous T-Cell Lymphoma (CTCL) who failed prior therapies.

Official Title
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A Phase 2, Open-Label, Multicenter Study of Single-Agent Enzastaurin in Patients With Relapsed Cutaneous T-Cell Lymphoma

Conditions
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Cutaneous T-Cell Lymphoma

Intervention / Treatment
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* Drug: Enzastaurin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed mycosis fungoides or Sezary Syndrome. Stage IB to IVB disease at screening. Recurrent or refractory disease after at least 1 prior systemic therapy. Have adequate organ function defined as: Hepatic: total bilirubin ≤1.5 times the upper limit of normal (ULN); alanine transaminase/aspartate transaminase (ALT/AST) ≤2.5 times the ULN. Renal: serum creatinine ≤1.5 times the ULN. Adequate bone marrow reserve: platelets ≥75 * 10^9/Liters (L); absolute neutrophil count (ANC) ≥1.0 * 10^9/L. At least 30 days must have passed since other treatment for CTCL. Exclusion Criteria: Receiving concurrent treatment for CTCL. Unable to swallow tablets. Receiving high potency oral or topical steroids. Low potency oral steroid may be permitted in participants who have been on a stable dose for at least 4 weeks prior to screening. Oral or topical antihistamine is allowed. Unable to discontinue use of carbamazepine, phenobarbital, or phenytoin. Have a serious concomitant systemic disorder or Human Immunodeficiency Virus (HIV). Have a serious cardiac condition such as myocardial infarction within past 6 months, angina, or heart disease as defined by the New York Heart Association (NYHA) Class III or IV. Have electrocardiogram (ECG) abnormalities. Are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzastaurin<br>Open Label | Drug: Enzastaurin<br>* 1125 milligrams (mg) loading dose then 500 mg, oral, daily, until disease progression<br>* Other names: LY317615;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Confirmed Complete Response (CR) or Partial Response (PR) Among Mycosis Fungoides (MF) and Sezary Syndrome (SS) Participants (Response Rate) | Response rate is percentage of participants with confirmed CR or PR as per modified Severity-Weighted Assessment Tool (mSWAT) for MF group; mSWAT and Sezary count for SS group. mSWAT is a weighted sum of percent (%) of total body surface area attributed to skin lesions which yield a mSWAT score [0 (unaffected) to 400 (severely affected)] transformed into responses. As per mSWAT (CR: No detectable malignant disease for ≥4 weeks; PR: ≥50% mSWAT score reduction from baseline). Sezary cells percentage in lymphocytes measured using flow cytometry. As per Sezary count (CR: Sezary cells <5%; PR: ≥50% reduction in Sezary cells from baseline). Response rate is calculated as total number of participants with CR or PR from the start of study treatment until PD or recurrence divided by the number of participants treated, then multiplied by 100. | Baseline to measured Progressive Disease (PD) [up to 9 cycles (28-day cycles)] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response for Responding Participants | Time from first confirmed response [Complete Response (CR) or Partial Response (PR)] until Progressive Disease (PD) as per mSWAT for MF group; mSWAT and Sezary count for SS group. mSWAT: weighted sum of percent (%) of total body surface area attributed to skin lesions; scores [0 (unaffected) to 400 (severely affected)] transformed into responses. As per mSWAT (CR: No detectable malignant disease for ≥4 weeks; PR: ≥50% reduction in mSWAT score from baseline; PD: ≥25% of mSWAT score from nadir). Sezary cells percentage in lymphocytes measured using flow cytometry. As per Sezary count (CR: Sezary cells <5%; PR: ≥50% reduction in Sezary cells from baseline; PD: ≥40% of Sezary cells from nadir). Responders or those who died without PD were censored at date of last progression-free disease assessment. Responders who received subsequent systemic anticancer therapy were censored at date of last progression-free disease assessment prior to post-discontinuation therapy. | Time of response to PD [up to 9 cycles (28-day cycles)] | 
| Time to Progression | Elapsed time from enrollment (baseline) to date of Progressive Disease (PD) as per mSWAT for Mycosis Fungoides (MF) group; mSWAT and Sezary count for Sezary Syndrome (SS) group. mSWAT: weighted sum of percent (%) of total body surface area attributed to skin lesions; scores [0 (unaffected) to 400 (severely affected)] transformed to responses. PD: ≥25% of mSWAT score from nadir. Sezary cells percentage in lymphocytes measured using flow cytometry. PD: ≥40% Sezary cells from nadir. Responders or those who died without PD were censored at the date of the last progression-free disease assessment. Responders who received subsequent systemic anticancer therapy were censored at the date of the last progression-free disease assessment prior to post-discontinuation therapy. | Baseline to measured PD [up to 9 cycles (28-day cycles)] | 
| Time to Objective Response for Responding Participants | Elapsed time from date of study enrollment (baseline) to first evidence of Complete Response (CR) or Partial Response (PR) as per mSWAT for Mycosis Fungoides (MF) group; mSWAT and Sezary count for Sezary Syndrome (SS) group. mSWAT: weighted sum of percent (%) of total body surface area attributed to skin lesions; scores [0 (unaffected) to 400 (severely affected)] transformed into responses. As per mSWAT (CR: No detectable malignant disease for ≥4 weeks. PR: ≥50% mSWAT score reduction from baseline). Sezary cells percentage in lymphocytes measured using flow cytometry. As per Sezary count (CR: Sezary cells <5%; PR: ≥50% reduction in Sezary cells from baseline). Response must be confirmed, but the time to objective response ended at the first assessment. Participants who were not confirmed responders did not contribute to the time to objective response calculation. | Baseline to confirmed response [up to 9 cycles (28-day cycles)] | 
| European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Utility Score United States (US) Index (Participant-Reported Measure of Health-State Utility) | EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (1 (no problem), 2 (some problems), and 3 (extreme problems)). These combinations of attributes were converted into a single summary health-state index score by applying weights from the US-specific value set to the scoring algorithm. The EQ-5D US value set of health state index scores ranged from 0 (worst imagined health state) to 1 (best imagined health state). | Baseline to study completion [up to 9 cycles (28-day cycles)], end of treatment reported | 
| Pruritus 5-Item Severity Assessment Questionnaire (Participant-Reported Experiences With Pruritus) | Participants assessed their present level of itch through the use of an 11-point numeric rating scale anchored at 0 (no itch) and 10 (itch as bad as can be imagined). | Baseline to study completion [up to 9 cycles (28-day cycles)], end of treatment reported | 
| Change From Baseline in Itchy Quality of Life (QoL) Domain and Total Scores (Participant-Reported Experiences With Pruritus) | The Itchy QoL is a non-validated 22-item questionnaire designed to assess pruritus-associated symptoms with a 7-day recall using 3 domains: Emotions (9 items), Functions (7 items) and Symptoms domain (6 items). Each Itchy QoL item was evaluated by level of itch frequency through the use of a 5-point adjectival scale 1 (never), 2 (rarely), 3 (sometimes), 4 (often), 5 (all the time). Unweighted means were calculated individually for the 3 domains each with scores range from 1 to 5 and the total score is expressed as the mean of the three dimension scores and ranges from 1 (no itch) to 5 (worst imaginable itch). | Baseline, up to study completion [up to 9 cycles (28-day cycles)], end of treatment reported | 
| Number of Participants With Adverse Events (AEs) or Deaths (Safety and Tolerability of Enzastaurin) | Data presented are the number of participants who experienced 1 or more AEs or any serious AEs (SAEs) regardless of causality, deaths during the study including 30 days after treatment discontinuation. A summary of SAEs and other non-SAEs regardless of causality is located in the Reported Adverse Events module. | Baseline to study completion [up to 9 cycles (28-day cycles)] plus 30-day safety follow-up |