A Study of Enzastaurin in Participants With Follicular Lymphoma

• ClinicalTrials.gov Identifier: NCT00475644
• Recruitment Status: Completed
• First Posted: May 21, 2007
• Results First Posted: November 5, 2018
• Last Update Posted: November 5, 2018
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

To evaluate the antitumor activity, as measured by tumor response rate, of enzastaurin in participants with Follicular Lymphoma (FL).

Condition or disease	Intervention/treatment	Phase
Lymphoma, Follicular	Drug: Enzastaurin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 66 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Enzastaurin in Participants With Follicular Lymphoma
• Study Start Date: May 2007
• Actual Primary Completion Date: April 2012
• Actual Study Completion Date: December 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Enzastaurin; Enzastaurin: 1125 milligram (mg) loading dose then 500 mg, oral daily, up to 3 years	Drug: Enzastaurin; Administered orally; Other Name: LY317615

Outcome Measures

Primary Outcome Measures :

1. Tumor Response Rate (RR) (Percentage of Participants Exhibiting Complete Response [CR] or Complete Response Unconfirmed [CRu] or Partial Response [PR]) [ Time Frame: Baseline to Measured Progressive Disease (up to 1559 Days) ]
   Tumor response rate is defined as the number of responders divided by the number of treated patients. A responder is a patient who exhibits a complete response (CR), complete response unconfirmed (CRu), or partial response (PR) as defined by Cheson et al. CR, the disappearance of target lesions and any pathological lymph nodes [target or non-target] taking as reference the baseline sum of diameters in response to treatment; CRu, complete disappearance of all detectable clinical and radiographic evidence of disease, return of spleen to non-palpable if involved, residual lymph node mass greater than 1.5 centimeters (cm) has regressed by more than 75%; PR, 50% decrease in the sum of the products of the greatest diameter (SPD) of the 6 largest dominant masses, no increase of other nodes, liver or spleen and no new sites of disease.

Secondary Outcome Measures :

1. Progression-Free Survival (PFS) [ Time Frame: Baseline to Measured Progressive Disease or Death from Any Cause (Up to 1559 Days) ]
   PFS is defined as the time from the date of study enrollment to the first date of measured progressive disease or death from any cause. For patients not known to have died as of the data cut-off date and who do not have objective progressive disease, PFS will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression or death, PFS will be censored at the date of last objective progression-free assessment prior to the initiation of postdiscontinuation anticancer therapy. For reference, PFS will also be calculated and analyzed based on an alternative definition of censoring: for each patient who is not known to have died or to have had objective progression of disease as of the data cut-off date, PFS will be censored for that analysis at the date of last prior contact.
2. Time to Response (TtR) [ Time Frame: Baseline to Date of Confirmed Response (Up to 890 Days) ]
   TtR is defined as the time from the date of study enrollment to the date of response (CR, CRu, or PR) for patients who have responded prior to receiving any subsequent anticancer therapy.CR, the disappearance of target lesions and any pathological lymph nodes [target or non-target] taking as reference the baseline sum of diameters in response to treatment; CRu, complete disappearance of all detectable clinical and radiographic evidence of disease, return of spleen to non-palpable if involved, residual lymph node mass greater than 1.5 centimeters (cm) has regressed by more than 75%; PR, 50% decrease in the sum of the products of the greatest diameter (SPD) of the 6 largest dominant masses, no increase of other nodes, liver or spleen and no new sites of disease.
3. Duration of Response (DoR) [ Time Frame: Time of Response to Measured Progressive Disease (Up to 1415 Days) ]
   DoR is defined as the time from the date when the measurement criteria are met for CR, CRu, or PR (whichever status is recorded first) until the date of first observation of measured progressive disease. For responding participants who die without progressive disease (including death from study disease), DoR will be censored at the date of death. For responding participants not known to have died as of the data cut-off date and who do not have progressive disease, DoR will be censored at the last objective progression-free assessment date prior to the data cut-off date. For responding participants who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to disease progression, DoR will be censored at the date of last objective progression-free assessment prior to the initiation of postdiscontinuation anticancer therapy.
4. Number of Participants With Response With Expression of Protein Biomarkers [ Time Frame: Baseline ]
   Correlative analyses of tumor RR for PKC-β2 (protein kinase C-β) protein expression. Immunohistochemistry (IHC) staining was performed to assess protein expression of PKC-β2 in cytoplasm reported as H scores (logistic model of response rate), which was derived from a weighted average of staining intensity (scale 0 to 3, increasing intensity) and percentage of positive cells (0 to 100%) at each staining intensity. PKC-β2 expression was further classified into high vs. low expression using the cutpoint of the median of the distribution of PKC-β2 H scores.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

All participants must:

1. Have had a histologically confirmed diagnosis of Grade 1 or 2 FL, according to World Health Organization classification (Harris et al. 1999), at the original time of diagnosis. Pathology must be confirmed locally prior to enrollment at the investigational site.
2. Have Ann Arbor Stage III or IV disease.
3. Must be chemo-naive OR have relapsed disease after receiving only one prior chemotherapy regimen. The chemotherapy must have been completed at least 6 months prior to first dose of study treatment. Relapse after one prior course of single-agent rituximab treatment (in the chemo-naive setting) is also allowed if completed at least 6 months prior to first dose of study treatment.
4. Participants must not require cytoreductive therapy for at least 3 months from first dose of study treatment, in the opinion of the investigator.
5. Previous radiation therapy is allowed, but should have been limited and must not have included whole pelvis radiation. Participants must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Prior radiotherapy must be completed 30 days before study entry. Lesions that have been irradiated cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy.

Exclusion Criteria:

Participants will be excluded from the study if they meet any of the following criteria:

1. Are unable to swallow tablets.
2. Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin.
3. Are receiving concurrent administration of any other antitumor therapy.
4. Are pregnant or breastfeeding.
5. Have a serious concomitant systemic disorder (including active bacterial, fungal, or viral infection) that, in the opinion of the investigator, would compromise the participant's ability to adhere to the protocol.

Contacts and Locations

Locations

United States, Arizona

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Casa Grande, Arizona, United States, 85222

United States, California

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La Verne, California, United States, 91750

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Los Angeles, California, United States, 90027

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Sacramento, California, United States, 95816

United States, Florida

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Fort Myers, Florida, United States, 33916

United States, Georgia

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Augusta, Georgia, United States, 30901

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Marietta, Georgia, United States, 30060

United States, Idaho

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Coeur d'Alene, Idaho, United States, 83814

United States, Indiana

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Lafayette, Indiana, United States, 47904

United States, Montana

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Billings, Montana, United States, 59101

United States, Ohio

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Cincinnati, Ohio, United States, 45242

United States, Oklahoma

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Lawton, Oklahoma, United States, 73505

United States, Pennsylvania

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Philadelphia, Pennsylvania, United States, 19107

United States, Tennessee

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Chattanooga, Tennessee, United States, 37404

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Memphis, Tennessee, United States, 38120

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Nashville, Tennessee, United States, 37203

United States, Virginia

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Richmond, Virginia, United States, 23230

United States, Wisconsin

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La Crosse, Wisconsin, United States, 54601

Germany

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Berlin, Germany, D-12203

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Bielefeld, Germany, D-33604

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Hamburg, Germany, D 21075

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Kiel, Germany, 24040

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Munich, Germany, 81377

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours,EST); Eli Lilly and Company

More Information

Additional Information:

Lilly Clinical Trial Registry 

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00475644
• Other Study ID Numbers: 8671; H6Q-MC-S011 ( Other Identifier: Eli Lilly and Company )
• First Posted: May 21, 2007
• Results First Posted: November 5, 2018
• Last Update Posted: November 5, 2018
• Last Verified: October 2018

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Follicular; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin