adenine and Lymphoma, Large B-Cell, Diffuse

adenine has been researched along with Lymphoma, Large B-Cell, Diffuse in 108 studies

Lymphoma, Large B-Cell, Diffuse: Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.

Research

Studies (108)

Authors

Clinical Trials (18)

Trial Overview

Trial Outcomes

Duration of Response (DoR): Study Cohort

DOR is defined as the interval between the date of initial documentation of a response including partial response with lymphocytosis (PRL) and date of first documented evidence of progressive disease or death or date of censoring. iWCLL 2008 criteria for progressive disease: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; >= 50% increase from nadir in existing lymph node or >=50% increase from nadir in sum of product of diameters of multiple nodes; >=50% increase from nadir in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (>=5*10^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology. (NCT02329847)
Timeframe: Up to 6 years 11 months

Duration of Stable Disease or Better: Study Cohort

Duration of stable disease or better was defined as duration from the start of the treatment until the criteria for progression were met. IWCLL 2008 criteria for progressive disease: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; >= 50% increase from nadir in existing lymph node or >=50% increase from nadir in sum of product of diameters of multiple nodes; >=50% increase from nadir in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology. (NCT02329847)
Timeframe: Up to 6 years and 11 months

Overall Response Rate (ORR) as Assessed International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008: Disease Cohort

ORR is percentage of participants achieving a complete response (CR), CR with incomplete marrow recovery (CRi), nodular partial response (nPR) or PR. IWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/L, platelets >100*10^9/L, Hgb >11 g/dL and absolute lymphocyte count <4000/mcL; CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but the bone marrow biopsy shows B-lymphoid nodules, may represent a clonal infiltrate; PR- >=50% drop in lymphocyte count from baseline or <=4.0*10^9/L with following: >=50% decrease in sum products of up to 6 lymph nodes, no new enlarged lymph nodes, When abnormal, >=50% decrease in enlargement of spleen from baseline or normalization and a response in 1 of following: Neutrophils >1.5*10^9/L, Platelets>100000/mcL and Hgb>11 g/dL or >=50% improvement over baseline in all. This outcome measure was planned to be analyzed for specified arm only. (NCT02329847)
Timeframe: Up to 6 years 11 months

Overall Response Rate (ORR) as Assessed Non-Hodgkin Lymphoma (NHL), Cheson 2014: Disease Cohort

ORR defined as percentage of participants achieving a CR, CRi, nPR or PR. As per Non-Hodgkin Lymphoma, Cheson 2014, CR is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR is >= 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. Progressive disease (PD) >= 50% increase from nadir in the sum of the products of at least two lymph nodes, or appearance of a new lesion greater than 1.5 cm in any axis even if other lesions are decreasing in size. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. This outcome measure was planned to be analyzed for specified arms only. (NCT02329847)
Timeframe: Up to 6 years 11 months

Overall Survival (OS): Study Cohort

OS was defined as duration from the date of first dose of study drug to the date of the participant's death. (NCT02329847)
Timeframe: Up to 6 years 11 months

Percentage of Participants With Lymphoma-related Symptoms: Study Cohort

Percentage of participants with lymphoma-related symptoms were reported. These symptoms included B-symptoms, recurrent fever, night sweats, weight loss, other disease-related symptoms, itching, fatigue, physical discomfort and any other. (NCT02329847)
Timeframe: Up to 6 years 11 months

Percentage of Participants With Treatment-emergent Adverse Event (TEAEs): Study Cohort

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs for the treatment phase included events with an onset date/time on or after the start of study intervention through end of study were considered as treatment-emergent. (NCT02329847)
Timeframe: Up to 6 years 10 months

Progression-free Survival (PFS): Study Cohort

PFS is defined as the duration from the date of first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first. Participants who were progression-free and alive or had unknown status were censored at the last tumor assessment. IWCLL 2008 criteria for progressive disease: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; >= 50% increase from nadir in existing lymph node or >=50% increase from nadir in sum of product of diameters of multiple nodes; >=50% increase from nadir in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology. (NCT02329847)
Timeframe: Up to 6 years 11 months

Event-Free Survival (EFS) - Activated B-Cell (ABC) Population

EFS: duration from randomization date to PD date, relapse from CR assessed by investigator, initiation of subsequent systemic antilymphoma therapy for either PET-positive/ biopsy-proven residual disease upon completion of >=6 cycles of R-CHOP therapy/death, whichever occurred first. Responses were based on Revised Response Criteria for Malignant Lymphoma. PD: any new lesion or increase by 50% of previously involved sites from nadir; PD criteria: Appearance of new nodal lesion 1.5 cm in any axis, 50% increase in SPD of >1 node or 50% increase in longest diameter of previously identified node 1 cm in short axis. CR: disappearance of all evidence of disease; CR criteria: nodal masses PET positive prior to therapy; mass of any size permitted if PET negative; regression to normal size on CT; spleen and liver: not palpable, nodules disappeared; bone marrow: infiltrate cleared on repeat biopsy. (NCT01855750)
Timeframe: Up to approximately 4.5 years

Event-Free Survival (EFS) - Intent-to-Treat (ITT) Population

EFS: duration from randomization date to disease progression(PD) date, relapse from complete response(CR) assessed by investigator, initiation of subsequent systemic antilymphoma therapy for either positron emission tomography(PET)-positive/ biopsy-proven residual disease upon completion of >=6 cycles of R-CHOP therapy/death, whichever occurred first. Responses were based on Revised Response Criteria for Malignant Lymphoma. PD: any new lesion or increase by 50% of previously involved sites from nadir; PD criteria: Appearance of new nodal lesion 1.5 cm in any axis, 50% increase in sum of product of diameters(SPD) of >1 node or 50% increase in longest diameter of previously identified node 1 cm in short axis. CR: disappearance of all evidence of disease; CR criteria: nodal masses PET positive prior to therapy; mass of any size permitted if PET negative; regression to normal size on CT; spleen and liver: not palpable, nodules disappeared; bone marrow: infiltrate cleared on repeat biopsy. (NCT01855750)
Timeframe: Up to 5.5 years

Overall Survival

Overall survival was defined as the duration from the date of randomization to the date of the participant's death. Median Overall Survival was estimated by using the Kaplan-Meier method. (NCT01855750)
Timeframe: Up to 5.5 years

Percentage of Participants Who Achieved Complete Response (CR)

Percentage of participants with measurable disease who achieved CR were reported. CR: disappearance of all evidence of disease. CR Criteria: Complete disappearance of all disease-related symptoms; all lymph nodes and nodal masses regressed to normal size (less than or equal to [<=]1.5 cm in greatest transverse diameter [GTD] for nodes greater than [>]1.5 cm before therapy). Previous nodes of 1.1 to 1.5 cm in long axis and greater than (>)1.0 cm in short axis before treatment decreased to <=1.0 cm in short axis after treatment. Disappearance of all splenic and hepatic nodules and other extranodal disease; a negative positron emission tomography (PET) scan. A posttreatment residual mass of any size but PET-negative; spleen and liver: not palpable, nodules disappeared; bone marrow: infiltrate cleared on repeat biopsy. (NCT01855750)
Timeframe: Up to approximately 4.5 years

Progression-Free Survival (PFS)

PFS was defined as the duration from the date of randomization to the date of progression, relapse from CR, or death, whichever occurred first. Responses were based on Revised Response Criteria for Malignant Lymphoma. Progressive Disease (PD): any new lesion or increase by 50% of previously involved sites from nadir; PD criteria: Appearance of new nodal lesion 1.5 centimeter (cm) in any axis, 50% increase in SPD of >1 node or 50% increase in longest diameter of previously identified node 1 cm in short axis. CR: disappearance of all evidence of disease; CR criteria: nodal masses PET positive prior to therapy; mass of any size permitted if PET negative; regression to normal size on CT; spleen and liver: not palpable, nodules disappeared; bone marrow: infiltrate cleared on repeat biopsy. (NCT01855750)
Timeframe: Up to approximately 4.5 years

Time to Worsening in the Lymphoma Subscale of Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)

Time to worsening in the Lymphoma subscale of the FACT-Lym, defined as the interval from the date of randomization to the start date of worsening of participant symptoms. Worsening was defined by a 5-point decrease from baseline. FACT-Lym Lymphoma subscale contains 15 questions, scores from 0 to 4 for each question (higher the worse). Lymphoma subscale score is the total of reverse scores, range 0 to 60. Higher scores indicate a better quality of life. (NCT01855750)
Timeframe: Up to approximately 4.5 years

Duration of Response (DOR)

Part 2: DOR will be measured from the time by which the measurement criteria are met for CR or PR until the first date by which recurrent or progressive disease is objectively documented. (NCT02142049)
Timeframe: From initial response date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose.

Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy

Part-1: Overall Response rate (ORR) will defined as the proportion of subjects who achieve either a CR or a PR according to the international Working Group Response Criteria for NHL as assessed by investigator. (NCT02142049)
Timeframe: 1 year after last subjects received the first dose

Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy-ORR

Part 2 - Overall Response rate will be defined as the proportion of subjects who achieve either a Complete Response or a Partial Response according to the international Working Group Response Criteria for NHL as assessed by investigator. (NCT02142049)
Timeframe: 1 year after last subjects received the first dose

Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability

Part-1: To determine the maximum tolerated dose (MTD) of the combination of ibrutinib and lenalidomide with dose adjusted EPOCH-R (NCT02142049)
Timeframe: 1 year after last subjects received the first dose

Number of Subjects With Adverse Events as a Measure of Safety and Tolerability

Part 2: The frequency (number and percentage) of treatment-emergent adverse events will be reported. (NCT02142049)
Timeframe: 1 year after last subjects received the first dose

Progression Free Survival (PFS) and Overall Survival (OS) as a Measure of Efficacy

Part 2: PFS will be measured as time from first study drug administration to disease progression or death from any cause. OS will be measured from the time of first study drug administration until the date of death using Kaplan-Meier methodology. (NCT02142049)
Timeframe: From initial dose date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose, up to 36 months at the most.

Complete Response Rate

Will be defined as complete response or incomplete blood count recovery. Estimated by the number of patients who achieve an incomplete blood count recovery or complete response divided by the total number of evaluable patients. All evaluable patients will be used for this analysis. Exact binomial 95% confidence intervals for the true complete response rate will be calculated in each arm. (NCT02332980)
Timeframe: 1 year

Confirmed All Response Rate of Patients Treated With Combination Therapy

Confirmed response rate will be estimated by the number of patients with an objective status of complete response, incomplete blood count recovery, nodular partial response, clinical complete response or partial response while on the combination therapy divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate to the combination will be calculated. In addition, the responders on this study will be further examined in an exploratory manner to determine if there are any patterns in prognostic factors or disease characteristics, including whether the patient had a Richter's transformation or ibrutinib-resistant disease, for both single agent pembrolizumab and combination therapy responders. (NCT02332980)
Timeframe: 1 year

Duration of Response

The distribution of duration of response will be estimated using the method of Kaplan-Meier. Duration of response (DR) is defined for all evaluable patients who have achieved a PR, nPR, CCR, CRi, or CR (Arms A and B) or PMR, CMR, PR or CR (Arm C) as the date at which the patient's objective status is first noted to be a PR, nPR, CCR, CRi, or CR (Arms A and B) or PMR, CMR, PR or CR (Arm C) to the earliest date relapse is documented. (NCT02332980)
Timeframe: 5 years

Incidence of Adverse Events

Will be measured per National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Adverse events will be evaluated for single-agent pembrolizumab in each arm and also for the combination of pembrolizumab and the signal inhibitor in Arm A and Arm C. This outcome is reported in the adverse events section of this report. (NCT02332980)
Timeframe: 1 year

Overall Survival

The distribution of overall survival will be estimated using the method of Kaplan-Meier. (NCT02332980)
Timeframe: 5 years

Progression-free Survival of Patients Treated in Single Agent Phase

The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT02332980)
Timeframe: 5 years

Progression-free Survival of Patients Treated With Combination Therapy

The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT02332980)
Timeframe: 5 years

Proportion of Patients Who Achieve a Confirmed Response

Confirmed response is defined to be a partial response, nodular partial response, clinical complete response, confirmed response with incomplete blood count recovery or confirmed response (Arm A and B), or complete metabolic response, partial metabolic response, partial response, or confirmed response (Arm C). The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial confidence intervals for the true success proportion will be calculated. (NCT02332980)
Timeframe: 1 year

Time to Next Treatment for Patients on Combination Therapy

The distribution of time to next treatment will be estimated using the method of Kaplan-Meier. (NCT02332980)
Timeframe: 5 years

Time to Next Treatment for Patients Treated With Single-agent Pembrolizumab

The distribution of time to next treatment will be estimated using the method of Kaplan-Meier. (NCT02332980)
Timeframe: 5 years

Treatment-free Survival of Patients Treated With Combination Therapy

The distribution of treatment-free survival will be estimated using the method of Kaplan-Meier. (NCT02332980)
Timeframe: 5 years

Treatment-free Survival of Patients Treated With Single-agent Pembrolizumab

The distribution of treatment-free survival will be estimated using the method of Kaplan-Meier. (NCT02332980)
Timeframe: 5 years

Phase 1b: Complete Response (CR) Rate

The CR rate was defined as the percentage of participants who achieve a CR, according to the Revised International Working Group Response Criteria for Malignant Lymphoma (Cheson 2007), as assessed by the Investigator in response-evaluable population, where CR=disappearance of all evidence of disease, as assessed by the Investigator. (NCT02077166)
Timeframe: Estimated median time on Phase 1b study was 59.6 months.

Phase 1b: ORR

The ORR was defined as the percentage of participants who achieve either a PR or CR, according to the Revised International Working Group Response Criteria for Malignant Lymphoma (Cheson 2007), as assessed by the Investigator in response-evaluable population, where CR=disappearance of all evidence of disease and PR=regression of measurable disease and no new sites. The 95% CI was calculated using the exact method. (NCT02077166)
Timeframe: Estimated median time on study in Phase 1b was 59.6 months.

Phase 1b: Recommended Phase 2 Dose of Lenalidomide in Combination With Fixed Doses of Ibrutinib and Rituximab in Participants With Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)

The dose levels of lenalidomide were explored, and dose escalation of lenalidomide followed the 3+3+3 dose escalation schema. A Dose Level Review Committee evaluated safety data following completion of each dose observation period of the Phase 1b portion. (NCT02077166)
Timeframe: Estimated median time on study in Phase 1b was 59.6 months.

Phase 2: CR Rate

The CR rate was defined as the percentage of participants who achieve a CR, according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (see Cheson, 2014 for detailed criteria) in response-evaluable population, as assessed by the Investigator. (NCT02077166)
Timeframe: Estimated median time on study in Phase 2 was 35.0 months.

Phase 2: Duration of Response (DOR)

DOR is defined as the time from the date of the first documented response (CR or PR) to the first documented evidence of disease progression (PD) according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (Cheson 2014) or death from any cause. For participants who had achieved an overall response but did not die or progress at the time of analysis, DOR was censored on the date of the last adequate post-baseline disease assessment, or on the date of the first occurrence of response (CR or PR) if there was no disease assessment afterwards. 2-sided 95% CI is estimated by Kaplan-Meier method. (NCT02077166)
Timeframe: Estimated median time on study in Phase 2 was 35.0 months.

Phase 2: Overall Response Rate (ORR)

The ORR was defined as the percentage of participants who achieve either a partial response (PR) or complete response (CR), according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (Cheson 2014), as assessed by the investigator in response-evaluable population. The 95% confidence interval (CI) was calculated using the exact method. (NCT02077166)
Timeframe: Estimated median time on study in Phase 2 was 35.0 months.

Phase 2: Overall Survival (OS)

OS is defined as the time from the date of the first dose of study drug to the date of death due to any cause. For participants not known to have died at or prior to the database lock date, OS data was censored at the date last known alive. Participants who withdrew consent prior to study closure were censored on the date of the consent withdrawal. 2-sided 95% CI was estimated by Kaplan-Meier method. (NCT02077166)
Timeframe: Estimated median time on study in Phase 2 was 35.0 months.

Phase 2: Progression Free Survival (PFS)

PFS is defined as the time from the date of the first dose of study drug to confirmed PD according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (Cheson 2014) or death from any cause, whichever occurred first. For participants without disease progression or death, PFS data was censored at the date of the last tumor assessment. 2 sided 95% CI is estimated by Kaplan-Meier method. (NCT02077166)
Timeframe: Estimated median time on study in Phase 2 was 35.0 months.

Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs

An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization > 24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. AEs that started or worsened during the treatment-emergent period and all possibly related or related AEs were considered TEAEs. Related events were those that were considered possibly related or related to study drug per investigator's judgment. Events were graded per the national Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03: Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening; grade 5=death. (NCT02077166)
Timeframe: From first dose of study drug up to 30 days after last dose of study drug. Phase 1b median duration of ibrutinib exposure was 4.4 months; median duration of lenalidomide exposure was 4.4 months; median total number of doses of rituximab received was 4.0.

Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs

An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization > 24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. AEs that started or worsened during the treatment-emergent period and all possibly related or related AEs were considered TEAEs. Related events were those that were considered possibly related or related to study drug per investigator's judgment. Events were graded per the national Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03: Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening; grade 5=death. (NCT02077166)
Timeframe: From first dose of study drug up to 30 days after last dose of study drug. Phase 2 median duration of ibrutinib exposure was 4.9 months; median duration of lenalidomide exposure was 4.7 months; median total number of doses of rituximab received was 5.0.

Number of Patients With Adverse Events as a Measure of Safety and Tolerability

Participants will be followed until progression of the disease or start of another anticancer treatment. The clinical database captured all AEs from baseline through end of treatment. Treatment Emergent AEs were collected pre-dose, at the beginning of each cycle and 30 days post last dose of study drug, unless related to study drug. (NCT01325701)
Timeframe: Adverse events determined to be related to study drug are collected from first dose until study exit (approximately 3 years).

Percentage of Patients With an Overall Response to Study Drug

The primary endpoint of the study was overall response rate (ORR), defined as the proportion of participants who achieved a best overall response of complete response (CR) or partial response (PR), according to the revised International Working Group Criteria for non-Hodgkin's lymphoma (Cheson et al, 2007), as assessed by the investigator. (NCT01325701)
Timeframe: The median follow up time on the study for all treated participants is 1.7 months (range 0.1- 32.3 months)

Ibrutinib and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765

"Treatment Group 1 PK collection schedule:~Cycle 1 Day 1: Pre-dose, 1, 2, 4, 7, and 24 hours post-dose Cycle 1 Day 8: Pre-dose, 1, 2, 4, 7, and 24 hours post-dose Cycle 1 Day 15: Pre-dose and 2 hours post-dose Cycle 1 Day 22: Pre-dose and 2 hours post-dose~Treatment Group 2 PK collection schedule:~Cycle 1 Day 8: Pre-dose, 1, 2, 4 and 7 hours post-dose Cycle 1 Day 15: Pre-dose and 2 hours post-dose Cycle 1 Day 22: Pre-dose and 2 hours post-dose Cycle 3 Day 1: Pre-dose, 1, 2, and 4 hours post-dose" (NCT01325701)
Timeframe: Performed during the first month of receiving study drug.

Reviews

14 reviews available for adenine and Lymphoma, Large B-Cell, Diffuse

Trials

14 trials available for adenine and Lymphoma, Large B-Cell, Diffuse

Other Studies

80 other studies available for adenine and Lymphoma, Large B-Cell, Diffuse