thalidomide and B-Cell Chronic Lymphocytic Leukemia

thalidomide has been researched along with B-Cell Chronic Lymphocytic Leukemia in 135 studies

Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.
thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide.
2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group.

Research

Studies (135)

Authors

Clinical Trials (23)

Trial Overview

Trial Outcomes

Overall Survival (OS)

Overall Survival (OS) is defined as the time from randomization to death from any cause. OS will be censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented. (NCT00774345)
Timeframe: Up to approximately 11 years

Progression Free Survival 2 (PFS2)

Progression Free Survival (PFS2) assessed by investigator is defined as the time from randomization to the second objective disease progression, or death from any cause, whichever occurs first. (NCT00774345)
Timeframe: Up to 6 years

Number of Participants With Adverse Events (AEs)

Number of participants with adverse events (AEs) that measure type, frequency and severity of AEs graded by National Cancer Institute Common Terminology Criteria (NCI CTCAE V 3.0) including any grade adverse events (AEs), Grade 3-4 AEs, AEs related to study drug, grade 3-4 AEs related to study drug. (NCT00774345)
Timeframe: From first dose to 30 days post last dose (up to 9 years)

Number of Participants That Experience Acute Haploidentical Alpha Beta Depleted Transplant (aGVHD)

Patients will be monitored for Grade IV aGVHD and organ toxicity. Acute assessment will be done using the modified Keystone (Glucksberg) consensus criteria. (NCT02193880)
Timeframe: From baseline and before day +100 of transplant.

Number of Participants That Experience Chronic Haploidentical Alpha Beta Depleted Transplant (cGVHD)

Patients will be monitored for Grade IV cGVHD and organ toxicity. Chronic assessment will be done using the conventional criteria. (NCT02193880)
Timeframe: From baseline and before day +100 of transplant.

Overall Response Rate (ORR)

ORR defined as number of participants with best response of Complete Response (CR) or Partial Response (PR) out of total number of participants. CR is defined as absence of lymphadenopathy, hepatomegaly or splenomegaly on physical exam. Normal Complete Blood Count (CBC) with polymorphonuclear leukocytes >1500/µL, platelets >100,000/µL, hemoglobin >11.0 g/dL (untransfused); lymphocyte count <5,000/µL; Bone marrow aspirate and biopsy must be normocellular for age with <30% of nucleated cells being lymphocytes. Lymphoid nodules must be absent. PR requires a 50% decrease in peripheral lymphocyte count from , 50% reduction in lymphadenopathy, and/or 50% reduction in splenomegaly/hepatomegaly for a period of at least two months from completion of therapy. These patients must have one of the following: Polymorphonuclear leukocytes 1,500/µL or 50% improvement ; Platelets >100,000/µL or 50% improvement ; Hemoglobin >11.0 g/dL (untransfused) or 50% improvement from pre-treatment value. (NCT00535873)
Timeframe: From 3 cycles (90 days) up to 6 cycles (approximately 180 days)

Kaplan-Meier Estimate of Duration of Response

Duration of response (DOR) was defined as the time from the first visit where PR, CRi, or CR was documented to progressive disease (PD). Duration of response was censored at the last date that the participant was known to be progression-free for participants who had not progressed at the time of analysis or who withdrew consent or were lost to follow-up prior to documentation of progression. (NCT00963105)
Timeframe: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.

Kaplan-Meier Estimate of Event-Free Survival

Event-free survival (EFS) is the interval between the start of treatment to the first sign of disease progression, or treatment for relapse or death (whichever occurred first). If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression. (NCT00963105)
Timeframe: From randomization until the end of the study; maximum time on study was 91 months.

Kaplan-Meier Estimate of Overall Survival

Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who had withdrawn consent or were lost to follow-up before death was documented. (NCT00963105)
Timeframe: From randomization until the end of the study; maximum time on study was 91 months.

Kaplan-Meier Estimate of Progression Free Survival

Progression-free survival (PFS) was calculated as the time from randomization to the first documented progression or death due to any cause during or after the treatment period, whichever occurred first. The progression date was assigned to the earliest time when any progression is observed without prior missing assessments. If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression. (NCT00963105)
Timeframe: From randomization until the end of the study; maximum time on study was 91 months.

Kaplan-Meier Estimate of Time to Progression

Time to progression (TTP) was defined as the time from randomization to the first documented progression. For participants who did not progress during the study, TTP was censored at the last adequate response assessment showing evidence of no disease progression. (NCT00963105)
Timeframe: From randomization until the end of the study; maximum time on study was 91 months.

Overall Response Rate (ORR)

ORR was defined as the percentage of patients with a complete response (CR), CR with incomplete bone marrow (BM) recovery (CRi) or partial response (PR) during treatment. Response was assessed according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines. Per the guidelines, a CR required peripheral blood lymphocytes below 4 x 10^9/L, absence of lymphadenopathy, no hepatomegaly or splenomegaly, absence of disease and blood counts neutrophils >1.5 x 10^9/L, platelets >100 x 10^9/L, hemoglobin (hgb) >11g/dL) and BM at least normocellular for age. CRi = CR with incomplete BM recovery. PR = required at least 2 months from end of treatment, a ≥50% decrease in peripheral blood lymphocyte count from the pre-treatment value and either a ≥ 50% reduction in lymphadenopathy or ≥50% reduction of liver enlargement or ≥50% reduction of spleen enlargement plus neutrophils >1.5 x 10^9/ or ≥50% increase, platelets >100 x 10^9/L or ≥50% increase, hgb 11 g/dL. (NCT00963105)
Timeframe: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.

Time to Response

Time to response (TTR) was calculated as the time from randomization to the first documented date of response (PR, CRi or CR) based on iwCLL guidelines for participants with an objective response during the treatment period. (NCT00963105)
Timeframe: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.

Number of Participants With Treatment-emergent Adverse Events

Adverse events (AEs) were graded for severity by the investigator according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 with the exceptions of hematologic toxicities and tumor lysis syndrome, according to the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening or disabling AE Grade 5 = Death The investigator determined the relationship of each AE to study drug based on the timing of the AE and whether other medications, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the observed event. (NCT00963105)
Timeframe: From first dose of study drug to 30 days after the last dose; the maximum duration of treatment was 251, 265, and 267 weeks in the 5 mg, 10 mg, and 15 mg treatment groups respectively.

Time to Progression

The primary objective is progression-free survival (PFS). Tumor measurements and disease assessments will be performed at the time of screening, following cycles 3 and 6 of induction chemotherapy, every 4 cycles during the maintenance portion of treatment, and at the end of treatment (EOT). Subjects with clinical evidence of progression prior to a planned disease assessment will be evaluated at the time of clinically suspected progression. Follow-up visits for disease assessment will occur every 3 months after the EOT visit until PD, initiation of alternate anti-neoplastic therapy, decision by the subject to withdraw from the study, or death. The follow-up period will begin after the EOT visit, and all subjects will be followed for at least 2 years after completion of therapy or until death or progression and until the last patient has been followed for at least 1 year following completion of therapy. (NCT01754857)
Timeframe: At least 24 months following completion of therapy, an average of 5 years

Count of Events Related to Toxicity

To determine toxicities observed with induction chemotherapy and maintenance therapy. Safety evaluations will be based on the incidence, intensity, and type of adverse events (AEs) and clinical laboratory results. Drug doses will be modified as required based on toxicity as assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. (NCT01754857)
Timeframe: Up to 30 months

Number of Patients Reaching Disease-free Survival (DSF) Overall

Response will be assessed by clinical examination, peripheral blood, bone marrow aspirate and biopsy, radiographic evaluation. Response will be evaluated at three different levels: clinical, cytometric and molecular. (NCT00727415)
Timeframe: After 6 months from study entry (end of treatment)

Number of Patients With Severe Infections

Severe infection requiring more than 2 weeks of antibiotic therapy. (NCT00727415)
Timeframe: At 24 months from study entry (end of follow-up)

Overall Complete Response (CR) Rate (Phase II)

Response will be assessed by clinical examination, peripheral blood, bone marrow aspirate and biopsy, radiographic evaluation. Response will be evaluated at three different levels: clinical, cytometric and molecular. (NCT00727415)
Timeframe: After 6 months from study entry (end of treatment).

Toxicity as Assessed by NCI CTCAE v3.0

Data from all subjects who receive any study drug will be included in the safety analyses. (NCT00727415)
Timeframe: At 24 months from study entry (end of follow-up)

Correlation Between Complete Response (CR) and Baseline Biologic Parameters (i.e., IgHV, CD38, Etc.).

(NCT00727415)
Timeframe: After 6 months from study entry (end of treatment).

Maximum Tolerated Dose of Lenalidomide (Phase I)

Maximum tolerated dose of lenalidomide given in combination with fludarabine. (NCT00727415)
Timeframe: The MTD of Lenalinomide will be evaluated during the two courses given with the escalated dose of Lenalinomide defined by the respective dose level.

Kaplan Meier Estimate for Overall Survival at the Final Analysis

Overall Survival is defined as the time between randomization and death from any cause. Overall survival was censored at the last date that the subject was known to be alive for participants who were alive as of the data cutoff date and for participants who were lost to follow-up before death was documented. (NCT00910910)
Timeframe: Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months

Kaplan Meier Estimate of Overall Survival

Overall Survival is defined as the time between randomization and death from any cause. (NCT00910910)
Timeframe: Up to data cut off of 31 March 2014; median follow-up for all participants was 18.8 months

Kaplan-Meier Estimate for Duration of Response

Duration of response was defined as the time from first nPR, PR, CRi, or CR to PD. Duration of response was censored at the last date that the patient was known to be progression-free for: 1) participants who had not progressed at the time of analysis; 2) participants who had withdrawn consent or were lost to follow-up prior to documentation of progression (NCT00910910)
Timeframe: Up to data cut-off of 18 Feb 2013; up to approximately 39 months

Kaplan-Meier Estimate for Duration of Response With a Later Cut-off Date of 31 March 2014

Duration of response was defined as the time from first nPR, PR, CRi, or CR to PD. Duration of response was censored at the last date that the patient was known to be progression-free for: 1) patients who had not progressed at the time of analysis; 2) patients who had withdrawn consent or were lost to follow-up prior to documentation of progression (NCT00910910)
Timeframe: Up to data cut-off of 31 March 2014; up to approximately 53 months

Kaplan-Meier Estimate of Progression Free Survival (PFS)

Progression-free survival was defined as the time from randomization to the first documented progression confirmed per investigator's assessment or death due to any cause on study, whichever occurred first. The progression date was assigned to the earliest time when any progression was observed without prior missing assessments. If withdrawal of consent or lost to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression (NCT00910910)
Timeframe: From first dose of study drug to date of data cut-off of 18 Feb 2013; up to approximately 39 months

Kaplan-Meier Estimate of Progression Free Survival (PFS) With a Later Cut-off Date of 14 March 2014

Progression-free survival was defined as the time from randomization to the first documented progression confirmed per investigator's assessment or death due to any cause on study, whichever occurred first. Progressive disease included lymphadenopathy, an appearance of any new lesion such as enlarged lymph nodes (> 1.5 cm), splenomegaly, hepatomegaly or other organ infiltrates, an increase by 50% or more in greatest determined diameter of any previous site or an increase by 50% or more in the sum of the product of diameters of multiple nodes. The progression date was assigned to the earliest time when any progression was observed without prior missing assessments. If withdrawal of consent or lost to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression. (NCT00910910)
Timeframe: From randomization to data cut off date of 31 March 2014; median follow up time for all participants was 12.6 months

Number of Participants Deaths During the Treatment and Survival Follow-Up Phase

The number of study participants deaths during the treatment and follow-up phase (NCT00910910)
Timeframe: From the first dose of study drug up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months

Percentage of Participants With a Best Overall Response Based on IWCLL Guidelines With a Later Cut-off Date of 31 March 2014

"A best overall response rate is a CR, CRi, nPR or PR and is defined as:~Complete Remission (CR):~No lymphadenopathy~No hepatomegaly or splenomegaly~Absence of constitutional symptoms~Polymorphonuclear leukocytes ≥ 1500/ul~No circulating clonal B-lymphocytes~Platelets > 100,000/ul~Hemoglobin > 11.0 g/dl~Normocellular <30% lymphocytes, no B-lymphoid nodules;~Incomplete Clinical Response (CRi):~• CR without bone marrow biopsy confirmation.~Nodular Partial Response:~• CR with the presence of residual clonal nodules.~Partial Response requires:~≥ 50% decrease in peripheral blood lymphocyte count~≥ 50% reduction in lymphadenopathy~≥ 50% reduction in size of liver and/or spleen~1 or more of the following:~Polymorphonuclear leukocytes ≥ 1500/ul~Platelets >100,000/ul" (NCT00910910)
Timeframe: Up to data cut-off of 31 March 2014; approximately 53 months

Percentage of Participants With the Best Overall Response Based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines

"A best overall response rate is a CR, CRi, nPR or PR and is defined as:~Complete Remission (CR):~No lymphadenopathy~No hepatomegaly or splenomegaly~Absence of constitutional symptoms~Polymorphonuclear leukocytes ≥ 1500/ul~No circulating clonal B-lymphocytes~Platelets > 100,000/ul~Hemoglobin > 11.0 g/dl~Normocellular <30% lymphocytes, no B-lymphoid nodules;~Incomplete Clinical Response (CRi):~• CR without bone marrow biopsy confirmation.~Nodular Partial Response (nPR):~• CR with the presence of residual clonal nodules.~Partial Response (PR) requires:~≥ 50% decrease in peripheral blood lymphocyte count~≥ 50% reduction in lymphadenopathy~≥ 50% reduction in size of liver and/or spleen~1 or more of the following:~Polymorphonuclear leukocytes ≥ 1500/ul~Platelets >100,000/ul" (NCT00910910)
Timeframe: Up to data cut-off date of 18 Feb 2013; approximately 39 months

Time to Response

Time to response was calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines (NCT00910910)
Timeframe: Up to data cut-off of 18 Feb 2013; up to approximately 39 months

Time to Response for a Later Cut-off Date of 31 March 2014

Time to response was calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines (NCT00910910)
Timeframe: Up to data cut-off of 31 March 2014; up to approximately 53 months

Number of Participants and Types of Subsequent Anti-cancer Therapies Received Post Treatment

Subsequent anti-cancer therapies administered to participants following the discontinuation of study drug (either Lenalidomide or Chlorambucil) (NCT00910910)
Timeframe: Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months

Number of Participants With Adverse Events (AEs)

AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death (NCT00910910)
Timeframe: From randomization up to data cut-off of 18 Feb 2013; Up to approximately 39 months; maximum duration of exposure for Lenalidomide was 1086 days and 406 days for Chlorambucil

Number of Participants With Adverse Events With a Later Cut-off Date of 31 March 2014

AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death (NCT00910910)
Timeframe: From randomization to the data cut-off date of 31 March 2014; Up to 53 months; maximum duration of exposure for Lenalidomide was 1140 days and 406 days for Chlorambucil

To Establish the Overall Response Rate Measured at 24 Weeks After First Dose of Lenalidomide Using This Dosing Regimen

To establish the overall response rate based on peripheral blood measures (absolute neutrophil count, platelets, and/or hemoglobin), lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; and bone marrow biopsy measured at 24 weeks after first dose of lenalidomide using this dosing regimen (NCT00439231)
Timeframe: 24 weeks of lenalidomide therapy

Overall Participant Response Rate: Percentage of Participants With Complete + Partial Response According to Revised National Cancer Institute-sponsored Working Group Guidelines

Complete response: Absence lymphadenopathy, hepatomegaly or splenomegaly & constitutional symptoms; Normal complete blood count (CBC) exhibited by polymorphonuclear leukocytes>1500/µL, platelets>100,000/µL, hemoglobin>11.0 g/dL (untransfused); lymphocyte count <5,000/µL; Bone marrow aspirate & biopsy normocellular for age with <30% nucleated cells lymphocytes; Absence Lymphoid nodules. Fulfillment CR criteria after induction with exception of treatment related persistent cytopenia & bone marrow lymphoid nodules both considered partial response; Partial response: Requires 50% decrease in peripheral lymphocytes from pre-treatment, 50% reduction in lymphadenopathy, &/or 50% reduction in splenomegaly/hepatomegaly for 2+ months from therapy completion. Additionally one following from pre-treatment: Polymorphonuclear leukocytes 1,500/µL or 50% improvement; Platelets>100,000/µL or 50% improvement; Hemoglobin>11.0 g/dL (untransfused) or 50% improvement. (NCT00759603)
Timeframe: Responses assessed after 12 cycles, up to 48 weeks with interim assessments performed after 3, 6 and 12 cycles.

Duration of Response

(NCT00096018)
Timeframe: 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years

Overall Responders (Complete and Partial Response)

Criteria for response were based on the Revised National Cancer Institute-sponsored Working Group Guidelines for response, which includes clinical, hematologic, and bone marrow features (Cheson, B.D., et al., National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87:4990-97.) (NCT00096018)
Timeframe: 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years

Complete Response

Analysis of the Primary Endpoint: The complete responses will be estimated by the number of patients with CR divided by the total number of evaluable patients. (NCT01723839)
Timeframe: 28 day cycle, up to 4 cycles

Overall Response Rate

Analysis of the other Secondary Endpoints: The overall response rate will be estimated by the number of patients with complete and partial responses divided by the total number of evaluable patients. (NCT01723839)
Timeframe: 28 day cycle, up to 6 cycles

Response Rate to Lenalidomide-dexamethasone + Rituximab Therapy in Relapsed Small B-cell Lymphoma With Rituximab Resistance

Response rate is defined as a complete response or partial response using anatomic criteria of the International Workshop Response Critieria (Cheson, 1999). (NCT00783367)
Timeframe: 3 months

Time Until Progression After Lenalidomide-dexamethasone + Rituximab Therapy in Relapsed Small B-cell Lymphomas With Rituximab Resistance

Progression free survival time in months (NCT00783367)
Timeframe: 9 years from enrollment of first subject

Number of Patients in Overall Response Categories

Overall Response defined as participant had either complete response (CR) or partial response (PR) assessed after three cycles, at six months and yearly thereafter using the NCI-Working Group Criteria: Complete Response, Complete Response with Nodules, Partial Response, or No Response. (NCT00267059)
Timeframe: Evaluated after three 28-day cycles of lenalidomide.

Reviews

37 reviews available for thalidomide and B-Cell Chronic Lymphocytic Leukemia

Trials

42 trials available for thalidomide and B-Cell Chronic Lymphocytic Leukemia

Other Studies

56 other studies available for thalidomide and B-Cell Chronic Lymphocytic Leukemia