Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Behaviors and Mental Disorders

Rare Diseases

Lymphoma

Lymphoma, B-Cell

Aggression

Lymphoma, Large B-Cell, Diffuse

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Antirheumatic Agents

Etoposide

Cytarabine

Rituximab

Melphalan

Etoposide phosphate

Antineoplastic Agents, Immunological

Immunologic Factors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Antimetabolites

Antiviral Agents

ZBEAM (Zevalin, BCNU, Etoposide, Aracytine, Melphalan) ASCT Rituximab

Zevalin 0.4 mCi/kg: D-14 BCNU 300 mg/m² : D-6 Etoposide 100 mg/m²/12h : D-6 D-5 D-4 D-3 Aracytine 200 mg/m²/12h : D-6 D-5 D-4 D-3 Melphalan 140 mg/m²: D-2

ZBEAM (Zevalin, BCNU, Etoposide, Aracytine, Melphalan)

ASCT

Christian Gisselbrecht, MD

Christophe Fruchart, MD

The purpose of this study is to evaluate the efficacy and the safety of a preparative regimen utilizing standard-dose Yttrium-90 Ibritumomab Tiuxetan (Zevalin) radioimmunotherapy combined with high-dose BEAM followed by ASCT after first line treatment in patients aged from 18 to 65 years with poor prognosis CD 20 Diffuse Large B-Cell lymphoma

Targeted Intensification With ZBEAM and Autologous Stem Cell Transplantation in Patients With High-grade B-Cell Lymphoma

Targeted Intensification by a Preparative Regimen for Patients With High-grade B-Cell Lymphoma Utilizing Standard-dose Yttrium-90 Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy (RIT) Combined With High-dose BEAM Followed by Autologous Stem Cell Transplantation (ASCT)

Bayer

Lymphoma Study Association

Lymphoma, Follicular

Diffuse Large B-Cell Lymphoma

Follicular Lymphoma

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Pidilizumab

The monoclonal antibody termed CT-011 (currently, pidilizumab).

IV infusion of 1.5 mg/kg of CT-011 on Day 1(60 to 90 days post autologous PBSCT). Treatment was repeated every 42 days for a total of three courses with treatment visits on Days 1, 43, and 85.

CT-011

Leo I Gordon, MD

Arnon Nagler, MD

Autologous peripheral blood stem cell transplantation combined with high dose chemotherapy is the treatment of choice given to patients with diffuse large-B cell lymphoma (DLBCL) following relapse of the disease. Although many people are cured of their lymphoma with this therapy, the disease comes back in a certain proportion of patients. The purpose of this study is to test the safety and effectiveness of the monoclonal antibody, CT-011, in patients with DLBCL who have received autologous peripheral blood stem cell transplantation. All final eligible patients will receive an IV infusion of CT-011 on Day 1 (30 to 90 days post autologous PBSCT). Treatment will be repeated every 42 days for a total of three courses with treatment visits on Days 1, 43, and 85. Follow-up for safety and clinical outcome will be conducted throughout the study till 18 months post autologous PBSCT. Approximately 70 patients will participate in this study.

CT-011 MAb in DLBCL Patients Following ASCT

Phase II Safety and Efficacy Study of the Monoclonal Antibody CT-011 in Patients With Diffuse Large B-Cell Lymphoma Following Autologous Stem Cell Transplantation

PFS (progression-free survival ) will be determined at the eligible patient populations

CureTech Ltd

CT-011 : IV infusion of 1.5 mg/kg of CT-011 on Day 1(30 to 90 days post autologous PBSCT). Treatment was repeated every 42 days for a total of three courses with treatment visits on Days 1, 43, and 85.

CT-011 Antibody

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Israel

India

Chile

Region of Enrollment

Director Clinical Resaerch

Patients who did not meet key study entry criteria were excluded from the eligible data set.

Progression-free Survival

CT-011: IV infusion of 1.5 mg/kg of CT-011 on Day 1(60 to 90 days post autologous PBSCT). Treatment was repeated every 42 days for a total of three courses with treatment visits on Days 1, 43, and 85.

Overall Survival

Overall Study

Gemcitabine

Oxaliplatin

1125 mg loading dose then 500 mg, oral, daily, until disease progression or 3 years

enzastaurin

1000 mg/m², IV, once, every two weeks, four to eight 2 week cycles

gemcitabine

375 mg/m², IV, once every 2 weeks, four to eight 2 week cycles

rituximab

100 mg/m², IV, once every two weeks, four to eight 2 week cycles

oxaliplatin

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)

The primary purpose of this study is to help answer the following research questions:

* To assess whether Enzastaurin combined with rituximab, gemcitabine and oxaliplatin (R-GEMOX) can help participants with Diffuse Large B-Cell Lymphoma (DLBCL) remain free from disease and thus live longer.
* To assess for any side effects that might be associated with enzastaurin and R-GEMOX .
* To look at the characteristics and levels of certain genes and proteins to learn more about DLBCL and how enzastaurin works in the body.
* To look at the level of enzastaurin in the body and how long it remains.

Chemotherapy for Participants With Lymphoma

An Open-label, Single Arm, Phase 2 Study of Rituximab, Gemcitabine and Oxaliplatin Plus Enzastaurin as Treatment for Patients With Relapsed Diffuse Large B-Cell Lymphoma

PFS is defined as the rate at 1 year from the date of first dose of study drug to the first date of measured PD or death from any cause and was determined using the distribution of overall PFS times. The PFS rate at 1 year was determined using Kaplan-Meier estimates. For participants not known to have died as of the data cut-off date and who do not have PD, PFS was censored at the date of the last progression-free disease assessment.

Assessment of response was based on the International Workshop to Standardize Response criteria for lymphoma (Cheson et al. 1999). CR is the complete disappearance of all detectable clinical and radiologic evidence of disease; all lymph nodes and nodal masses must have regressed to normal size (≤1.5 cm in their greatest transverse diameter for nodes \>1.5 cm before therapy).CRu is as CR but with 1 or more of the following features: A residual lymph node mass \>1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameters (SPD) and/or indeterminate bone marrow with normalization of all biologic abnormalities. PR is regression of more than 50% (SPD) of all measurable lesions, disappearance of nonmeasurable lesions and no new lesion. For each response category the number of participants with this response will be divided by the total number of participants treated to achieve the response rate.

PFS was defined as time from randomization until the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) or death from any cause; by Investigator assessment. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter of target lesions taking as reference the smallest sum longest diameter since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s).

PFS rate was defined as the rate of PFS at 2 year from the date of first dose of study drug and was determined using the distribution of overall PFS times.

PFS rate was defined as the rate of PFS at 4 year from the date of first dose of study drug and was determined using the distribution of overall PFS times.

For participants not known to have died as of the data cut-off date and who did not have PD, PFS was censored at the date of the last progression-free disease assessment.

Overall survival was defined as the time from the date of first dose of study drug to the date of death from any cause. For participants who were not still alive at the time of analysis, survival time was censored at the last contact date. For participants not known to have died as of the cut-off date for analysis,OS was censored at the last contact date for participants in post-discontinuation.

Event-free survival time was defined as the time from the date of first dose of study drug to the first date of measured PD,or start of a new treatment for the lymphoma, or death from any cause. For participants not known to have events as of the data cut-off date, EFS was censored at the date of the last tumor assessment.

PFS based on DLBCL molecular subtypes (GCB vs non-GCB) were determined. The molecular characterization of germinal center B-cells (GCBs) vs. non-GCBs was analyzed as separate combination immunohistochemistry (IHC) markers based on the Hans algorithms. Molecular subtype was included as class effect in the analytical models, adjusting for International Prognostic Index (IPI) score.

Reported PFS was based on PKCB2 protein expression assessed by immunohistochemistry (scored in 10% increments for percent of tumor cells). Protein expression levels was grouped into high and low in association with the clinical endpoints. Grouping was based on 1) a pre-specified threshold provided by the pathologist at Cleveland Clinic for the diffuse large B-cell lymphoma (DLBCL)-prognostic markers, and 2) a median cut-point for the enzastaurin-specific markers.

Cmax,ss is defined as the maximum observed drug concentration during a dosing interval at steady state. Non-Compartmental Pharmacokinetic Parameters for Total Analyte (Enzastaurin + LSN326020). LSN326020 is Enzastaurin's major active metabolite.

AUCτ,ss is defined as the area under the concentration versus time curve during 1 dosing interval at steady state.

DFS was calculated as the duration from date of first dose of study drug to the date of first relapse event after CR or CRu or death from any cause. Participants who have not experienced an event at the time of analysis were censored at the most recent date of disease assessment. Events are relapse after a CR or CRu. Related death or death from unknown cause was considered as an event. Unrelated death was not considered as an event and the participant was censored at the time of death for this analysis. Unrelated death was defined as death from a cause not related to the lymphoma, any examination done for the lymphoma, or any treatment of the lymphoma.

Duration of tumor response was defined as the time from the date when the measurement criteria were met for CR and CRu or PR (whichever status was recorded first) until the date of first observation of objective disease progression. For responding patients who died without objective PD (including death from study disease), duration of response was censored at the date of the last objective progression-free disease assessment. For responding patients not known to have died as of the data cut-off date and who do not have objective PD, duration of response was censored at the date of the last objective progression-free disease assessment. For responding patients who received subsequent systemic anticancer therapy (after discontinuation from the study chemotherapy) prior to objectively determined disease progression, duration of response was censored at the date of the last objective progression-free disease assessment prior to post-discontinuation therapy.

Eli Lilly and Company

enzastaurin: 1125 mg loading dose then 500 mg, oral, daily, until disease progression or 3 years

gemcitabine: 1000 mg/m2, IV, once, every two weeks, four to eight 2 week cycles

rituximab: 375 mg/m2, IV, once every 2 weeks, four to eight 2 week cycles

oxaliplatin: 100 mg/m2, IV, once every two weeks, four to eight 2 week cycles

Enzastaurin + R-GEMOX

Enzastaurin: 1125 milligram (mg) loading dose then 500 mg, orally, daily with Gemcitabine: 1000 milligram per square meter (mg/m²) administered intravenously (IV); Rituximab: 375 mg/m² IV; Oxaliplatin: 100 mg/m² IV all given once every 2 weeks (1 Cycle) for 4 Cycles for Induction. If responding participants receive 4 additional Cycles for consolidation, Enzastaurin will be given as maintenance until Progressive Disease/Toxicity or up to 3 years.

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Russia

France

Germany

Chief Medical Officer

All randomized participants who received at least 1 dose of study drug. Participants censored =14

Percent of Participants With Progression Free Survival (PFS) After 1 Year Treatment

End of 4 cycles

End of 8 cycles

All randomized participants who received at least 1 dose of study drug.

Overall Response Rate (ORR) - Percentage of Participants Achieving Complete Response (CR) or Complete Response Unconfirmed (CRu) or Partial Response (PR) (Response)

2 Years

4 Years

All randomized participants who received at least 1 dose of study drug. 8 participants were censored.

Percent of Participants With Progression-Free Survival (PFS) After 2 Years and 4 Years of Treatment

1 Year

All randomized participants who received at least 1 dose of study drug. 14 participants were censored.

Percent of Participants With Overall Survival (OS) After 1 Year, 2 Years and 4 Years

All randomized participants who received at least 1 dose of study drug. 6 participants were censored.

Percent of Participants With Event Free Survival (EFS) After 1 Year, 2 Years and 4 Years

Non-GCB

All randomized participants who received at least 1 dose of study drug and had evaluable samples.

Progression-Free Survival (PFS ) of Participants With Diffuse Large B-cell Lymphoma (DLBCL) Germinal-Center B-cells (GCB) Versus Non-GCB Molecular Subtypes (Assessment of Biomarkers Relevant for Enzastaurin)

Comparing High Expression versus Low Expression

High Expression

Low Expression

PFS of Participants With Diffuse Large B-cell Lymphoma (DLBCL) Protein Kinase C Beta 2 (PKCB2) Expression (Assessment of Biomarkers Relevant for Enzastaurin)

All randomized participants who received at least 1 dose of study drug and evaluable PK data.

Pharmacokinetics (PK): Maximum Observed Drug Concentration During a Dosing Interval at Steady State(Cmax,ss) for Total Analyte [Characterization of Pharmacokinetics of Enzastaurin and Its Metabolites]

All randomized subjects who received at least 1 dose of study drug and evaluable PK data.

PK: Area Under the Concentration vs. Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) for Total Analyte

All randomized participants who received at least 1 dose of study drug. 7 participants were censored.

Percent of Participants With Disease-Free Survival (DFS) at 1 Year, 2 Years and 4 Years

All randomized participants who received at least 1 dose of study drug. Participants censored =13.

Duration of Tumor Response (DOR)

Enzastaurin: 1125 milligram (mg) loading dose then 500 mg, orally, daily with Gemcitabine: 1000 milligram per square meter (mg/m²) administered intravenously (IV); Rituximab: 375 mg/m² IV; Oxaliplatin: 100 mg/m² IV all given once every 2 weeks (1 Cycle) for 4 Cycles for Induction. If responding participants receive 4 additional Cycles for consolidation, Enzastaurin will be given as maintenance until Progressive Disease (PD)/Toxicity or up to 3 years.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Targeted Intensification With ZBEAM and Autologous Stem Cell Transplantation in Patients With High-grade B-Cell Lymphoma	NCT00689169	Lymphoma, Large...	ZBEAM (Zevalin,... ASCT Rituximab	18 Years - 65 Years	Lymphoma Study Association
CT-011 MAb in DLBCL Patients Following ASCT	NCT00532259	Lymphoma, Large... Lymphoma, Mixed... Primary Mediast...	CT-011	18 Years -	CureTech Ltd
Chemotherapy for Participants With Lymphoma	NCT00436280	Lymphoma, Large...	enzastaurin gemcitabine rituximab oxaliplatin	60 Years -	Eli Lilly and Company
Chemotherapy for Participants With Lymphoma	NCT00436280	Lymphoma, Large...	enzastaurin gemcitabine rituximab oxaliplatin	60 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for lymphoma, large cell, diffuse