A Study of Participants With Lymphoma Who Take R-CHOP and Enzastaurin Compared to Participants Who Take R-CHOP Only

Phase 2

Completed

• Conditions: Lymphoma
• Interventions: Drug: rituximab; Drug: enzastaurin; Drug: cyclophosphamide; Drug: doxorubicin; Drug: vincristine; Drug: prednisone

• Registration Number: NCT00451178
• Lead Sponsor: Eli Lilly and Company

Brief Summary

To compare R-CHOP plus enzastaurin versus R-CHOP for progression-free survival (PFS) time measured in participants with intermediate and/or high risk for diffuse large B-cell lymphoma (DLBCL) receiving first-line treatment.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2007-03-21
• Study First Submitted QC: 2007-03-21
• Study First Posted: 2007-03-23
• Study Start: 2007-05
• Primary Completion: 2012-02
• Disposition First Submitted: 2012-05-24
• Disposition First Submitted QC: 2012-05-24
• Disposition First Posted: 2012-06-01
• Study Completion: 2013-01
• Results First Submitted: 2020-06-09
• Status Verified: 2020-07
• Results First Submitted QC: 2020-07-20
• Last Update Submitted: 2020-07-20
• Results First Posted: 2020-07-21
• Last Update Posted: 2020-07-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 101

Inclusion Criteria

Participants must:

1. Have a histologically confirmed diagnosis of DLBCL based on the World Health Organization classification (Harris et al. 1999) at the time of original diagnosis. Pathology must be reviewed and confirmed prior to enrollment at the investigational site where the participant is entered. Participants with a prior history of an indolent lymphoma or a histological diagnosis of follicular Grade 3 lymphoma will not be eligible for enrollment.

2. Have received no prior chemotherapy.

3. Have an International Prognostic Index (IPI) score ≥2 at time of original diagnosis.

4. Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology group (ECOG) scale.

5. Have adequate organ function as follows:

   • Hepatic: total bilirubin ≤1.5 times the upper limit of normal (x ULN); alanine transaminase (ALT) and aspartate transaminase (AST) ≤1.5 x ULN, (≤5 x ULN, if liver involvement).
   • Renal: serum creatinine ≤1.5 x ULN.
   • Adequate bone marrow reserve: platelets ≥75 x 10^9 per Liter (L), absolute neutrophil count (ANC) ≥1.0 x 10^9 per L, unless there is bone marrow involvement.

Exclusion Criteria

Participants must not: 6. Have received treatment within the last 30 days with a drug (not including enzastaurin) that has not received regulatory approval for any indication at the time of study entry. 7. Are receiving concurrent administration of any other systemic anticancer therapy. 8. Are pregnant or breastfeeding. 9. Are unable to swallow tablets. 10. Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin at least 14 days prior to study enrollment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
R-CHOP and Enzastaurin	vincristine	R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
R-CHOP and Enzastaurin	prednisone	R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
R-CHOP and Enzastaurin	doxorubicin	R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
R-CHOP	rituximab	R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
R-CHOP	cyclophosphamide	R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
R-CHOP	doxorubicin	R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
R-CHOP	vincristine	R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
R-CHOP	prednisone	R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
R-CHOP and Enzastaurin	enzastaurin	R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
R-CHOP and Enzastaurin	cyclophosphamide	R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.
R-CHOP and Enzastaurin	rituximab	R-CHOP includes rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment therapies.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) Time	Randomization to measured PD or death from any cause (up to 55 months)	PFS time is the elapsed time from the date of randomization to the first date of objectively-determined PD or death from any cause. PD was assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new or increased lymph nodes/masses and reappearance of bone marrow infiltrate. For participants not known to have died as of the data cut-off date and who did not have objective PD, PFS was censored at the date of the last objective progression-free disease assessment. For participants who received subsequent anticancer therapy (other than enzastaurin maintenance therapy) prior to objectively determined disease progression or death, PFS was censored at the date of the last objective progression-free disease assessment prior to the date of subsequent therapy.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Complete Response (CR and CRu) and Objective Response [CR, CRu, and Partial Response (PR)] (Overall Response Rate)	Baseline through long-term follow-up (up to 2 years post last dose)	CR, CRu, and PR were defined using International Working Group recommendations (Cheson et al. 1999). CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow must be negative if positive at baseline. Normalization of markers. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate bone marrow. PR is a 50% decrease in the sum of the products of diameters for up to 6 identified dominant lesions, including splenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. The percentage of participants with complete response (CR/CRu) and objective response (Cr/CRu/PR)=(Number of participants whose best overall response was CR/CRu or Cr/CRu/PR)/(Number of participants treated)\*100.
Percentage of Participants With Complete Response (CR/CRu) and/or Post-Baseline PET-Negative Scan (Concordance Between Response and PET Scan)	Cycle 6 (21 days/cycle)	Lesion response was assessed according to International Working Group recommendations (Cheson et al. 1999). CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow must be negative if positive at baseline. Normalization of markers. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate bone marrow. Percentage of participants with CR/CRu and/or PET-negative scan=(Number of participants with complete response and/or PET-negative scan at Cycle 6)/(Number of participants with a PET-positive scan at baseline)\*100.
Event-Free Survival (EFS)	Randomization to measured PD, start of new therapy, or death from any cause (up to 55 months)	EFS is the elapsed time from the date of randomization to the first date of objectively-determined PD, institution of a new anticancer treatment (other than maintenance therapy), or death from any cause. PD was assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new or increased lymph nodes/masses and reappearance of bone marrow infiltrate. For participants not known to have died as of the data cut-off date, who did not have objectively determined disease progression, and who were not treated with a new anticancer treatment, EFS was censored at the date of the last objectively determined disease-free assessment.
Percentage of Participants Alive Progression-Free at Year 2 (2-Year PFS Rate)	Randomization to measured PD (up to Year 2)	PD was assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new or increased lymph nodes/masses and reappearance of bone marrow infiltrate. Percentage of participants alive progression-free at Year 2=(Number of participants alive progression free at Year 2)/(Number of participants assessed)\*100.
Percentage of Participants With a PET-Negative Scan (PET-Negative Rate)	Cycle 6 (21 days/cycle)	The percentage of participants with a PET-negative scan=(Number of participants who had a PET-negative scan at Cycle 6)/(Number of participants who had a PET-positive scan at baseline)\*100.
Overall Survival (OS)	Baseline to death from any cause (up to 55 months)	OS is the elapsed time from the date of study enrollment (baseline) to the date of death from any cause. For participants not known to have died as of the data cutoff date, OS was censored at the last contact date or last date known to be alive, whichever was later.
Duration of Complete Response (CR or CRu)	Time of response to PD (up to 55 months)	Duration of response (DOR) either CR or CRu: Elapsed time from date CR or CRu criteria met to first objectively-determined PD. For responding participants (pts) who died without PD and pts not known to have died as of data cut-off date, who did not have PD, DOR censored at date of last objective progression-free disease assessment. For responding pts who received subsequent systemic anticancer therapy (other than enzastaurin maintenance therapy) prior to PD, DOR was censored at date of last objective progression-free disease assessment prior to subsequent therapy. CR and CRu defined using International Working Group recommendations (Cheson et al. 1999). CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate BM.
Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died (Evaluate Toxicity and Tolerability of R-CHOP Plus Enzastaurin)	First dose through 30 days post study treatment discontinuation (up to 56 months)	Data presented are the number of participants who experienced at least 1 TEAE, Grade 3 or 4 Common Terminology Criteria for Adverse Events (CTCAE), serious adverse event (SAE), as well as the number of participants who discontinued due to an adverse event (AE) or SAE, who died on therapy, died within 30 days post treatment or within 60 days of first dose. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
PFS of Participants With High or Low Expression of Protein Biomarkers and Correlation of Biomarkers to PFS	Randomization to measured PD or death from any cause (up to 55 months)]	Reported is PFS of participants (pts) with high or low biomarker expression levels. PFS: time from randomization to first date of PD/death from any cause. PD assessed according to International Working Group recommendations (Cheson et al. 1999). PD: Enlarging liver/spleen nodules, new/increased lymph node/masses and reappearance of bone marrow infiltrate. For pts who had subsequent anticancer therapy, PFS censored at date of last assessment prior to subsequent therapy. Biomarkers and number of pts censored: EIF4EBP1 Cytoplasm (C) 4,3,7,3; EIF4EBP1 Nucleus (N) 0,2,11,4; EIF4E C 5,2,6,4; EIF4E N 0,0,11,6; HDAC2 N 5,1,5,5; PCREB N 5,3,6,4; PEIF3746 C 4,2,7,4; PEIF3746 N 5,2,6,4; PEIFS209 C 5,2,5,4; PEIFS65 N 7,2,4,4; PEIFT70 C 5,2,6,4; PEIFT70 N 6,4,5,2; P GSK3B C 7,3,4,3; PKCb2 C 4,3,7,3; PS6 C 9,4,1,1; PTEN C 5,2,6,4; PTEN N 3,0,8,6. Correlation of biomarkers with PFS (statistical analyses) reported if high expression groups combined and low expression groups combined each had ≥10 pts.

Trial Locations

Locations (1)

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.; 🇺🇸 La Crosse, Wisconsin, United States