Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Chlorambucil

Antineoplastic Agents, Alkylating

Alkylating Agents

chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 treatment cycles

2mg tablets, chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles

chlorambucil, tablets

GSK Clinical Trials

This study is an open-label, single arm, phase II study of chlorambucil in subjects with previously untreated CLL.

The primary objective is to evaluate the response to chlorambucil in Japanese subjects with previously untreated CLL.

Secondary objectives are to evaluate efficacy, safety and pharmacokinetics of chlorambucil in Japanese subjects.

This study is an open-label, single arm, phase II study of chlorambucil in subjects with previously untreated CLL.

The primary objective is to evaluate the response to chlorambucil in Japanese subjects with previously untreated CLL.

Secondary objectives are to evaluate efficacy, safety and pharmacokinetics of chlorambucil in Japanese subjects.

Chlorambucil is an effective and well-tolerated chemotherapeutic agent currently approved for treatment of chronic lymphocytic leukemia (CLL) in the United States of America (US), European Union (EU) and other countries globally but not in Japan. Other more aggressive treatment options such as a combination of fludarabine (F) and cyclophosphamide are available, but are associated with significantly greater toxicities. The addition of ofatumumab to chlorambucil offers potentially a more effective therapy, with limited additional toxicity.

Study OMB110911 has been conducted mainly in the US and EU to evaluate progression-free survival (PFS) and overall response (OR) in subjects with previously untreated CLL with ofatumumab in combination with chlorambucil versus (vs.) chlorambucil monotherapy.

The objective of this study is to evaluate overall response of chlorambucil in Japanese subjects with previously untreated CLL.

A Phase II, Open Label, Single Arm, Multicenter Study of Chlorambucil in Japanese Previously Untreated Patients With Chronic Lymphocytic Leukemia

According to the criteria based on the 2008 revision of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) of the National Cancer Institute-Sponsored Working Group Guidelines (NCI-WG), participants with complete remission (CR), nodular partial remission (nPR), complete remission-incomplete (CRi) and partial remission (PR) were classified as responders, while stable disease (SD) and progressive disease (PD) were classified as non-responders. Participants with unknown or missing responses were considered as non-responders. Assessment was completed by the Investigator, Independent Review Committee (IRC), and IRC with Computed Tomography (CT).

OR is defined as the number of participants achieving either a confirmed CR or PR. Assessment was completed by the Investigator, IRC, and IRC with CT. CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) \> 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils \>1500 per microliter (µL), platelets (PL) \>100,000/µL, hemoglobin (Hb) \>11 grams/deciliter (g/dL), lymphocytes (LC) \<4000/µL, bone marrow (BM) sample must be normocellular for age, \<30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: \>=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL \>100,000/µL or 50% improvement over Baseline (BL), Hb \>11 g/dL or 50% improvement over BL. nPR: persistent nodules BM.

Progression-free survival (PFS) is defined as the time from the start of treatment of investigational product until the first documented sign of PD or death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlargerd lymph nodes (\>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Par. who were alive and had not progressed at the time of analysis or if a progression event or death occurred after extensive lost-to-follow-up time or if new anti-cancer therapy was started were censored at the date of the last visit with adequate assessment.

Overall survival is defined as time from the start of treatment until death due to any cause. Participants who had not died were censored at the date of last contact.

Time to response is defined as time from the start of treatment until the first response (CR/PR). Time to Response analyses was restricted to the subgroup of the population who experienced an overall response (CR/ nPR/CRi/PR) during the study. CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) \> 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils \>1500 per microliter (µL), platelets (PL) \>100,000/µL, hemoglobin (Hb) \>11 grams/deciliter (g/dL), lymphocytes (LC) \<4000/µL, bone marrow (BM) sample must be normocellular for age, \<30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: \>=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL \>100,000/µL or 50% improvement over Baseline (BL), Hb \>11 g/dL or 50% improvement over BL. nPR: persistent nodules BM.

Duration of response is defined as the time from the initial response (CR or PR) until progression or death. CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) \> 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils \>1500 per microliter (µL), platelets (PL) \>100,000/µL, hemoglobin (Hb) \>11 grams/deciliter (g/dL), lymphocytes (LC) \<4000/µL, bone marrow (BM) sample must be normocellular for age, \<30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: \>=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL \>100,000/µL or 50% improvement over Baseline (BL), Hb \>11 g/dL or 50% improvement over BL. nPR: persistent nodules BM.

Time to next CLL therapy is defined as the time from start of treatment until the first administration of the next CLL treatment other than chlorambucil administrations scheduled in this study. Time to next CLL therapy was restricted to the subgroup of the population who receive a next CLL therapy after experiencing disease progression.

ECOG PS is a scale to assess disease progression, extent to which disease affects the daily living abilities and determines appropriate treatment and prognosis. It is scored on a scale of 0 to 5 as, 0 (fully active), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), 2 (ambulatory and capable of all self cares but unable to carry out any work activities, Up and about \> 50% of waking hours), 3 (capable of only limited self cares, confined to bed or chair \> 50% of waking hours), 4 (completely disabled, cannot carry on any self cares, totally confined to bed or chair), 5 (death). Improvement is defined as decrease from baseline by at least one step on the ECOG performance status scale (yes/no). Baseline was last pre-dose assessment performed on Cycle 1 Day 1(C1 D1). When C1 D1 was missing, the last assessment performed prior to pre-dose C1 D1 was used. It was performed on Day 1 of each cycle and follow-up (FU).

The number of participants with no B-symptoms (no night sweat, no weight loss, no fever and no extreme fatigue) and the number of participants with at least one of the B-symptoms are summarized by assessment time. The presence of the B-symptoms was assessed at Baseline, Day 1 of each treatment cycle and follow-up (FU). Baseline was the last pre-dose assessment performed at C1 D1.

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, is a congenital anomaly/birth defect or is associated with protocol specified liver injury and impaired liver function or is any protocol specific AEs.

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product. Non-hematologic AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE V4.03): Grade 0, none; Grade 1, mild; Grade 2, moderate; Grade 3, severe or medically significant; Grade 4, life-threatening consequences; Grade 5, death related to AE

Number of participants with a Grade 3 or Grade 4 adverse event of infection or myelosuppression (anemia, neutropenia, and thrombocytopenia) are presented. Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. AEs were graded according to NCI common terminology criteria for adverse events (CTCAE) grade, version 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).

Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants.Peripheral samples were collected for the analysis of IgA, IgG, and IgM at Baseline and 28 days after Day 1 of the last treatment cycle (FU 1-PDFU 1) for all participants, and 168 days after day of FU 1-PDFU 1 for participants with CR, PR, and SD. Baseline was the last pre-dose assessment performed on Cycle 1-Day 1. The the last assessment performed prior to pre-dose Cycle 1-Day 1 was used if Cycle 1-Day 1 was missing. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

MRD refers to the small number of leukemic cells that remain in the participant during treatment or after treatment at the time the participant achieved a confirmed CR and in whom bone marrow test was performed. A bone marrow sample was examined by flow cytometry (Cluster of differentiation \[CD\]5, CD19, CD20, and CD23). MRD positive is defined as more than one CLL cell per 10000 leukocytes.

Blood samples were collected at the Baseline (Day 1 of Cycle 1) visit for prognostic biomarker Beta 2 microglobulin measurements.

Peripheral samples were collected for the analysis of complement CH50 at Baseline (Day 1 of Cycle 1) and after completion of Cycle 4 (Day 85).

Blood samples for pharmacokinetic (PK) analysis of chlorambucil were collected on Day 1 and Day 4 in Cycle 1, and on Day 1 in Cycle 3. In each sampling, blood samples (2 milliliter \[mL\]/sample) were collected at pre-dose, and 15 minute (min), 30 min, 1 hour (hr), 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. Maximum serum concentration (Cmax), minimum serum concentration (Cmin) were determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Blood samples for PK analysis of chlorambucil were collected on Day 1 and Day 4 in Cycle 1, and on Day 57 in Cycle 3. In each sampling, blood samples (2 mL/sample) were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. AUC from time zero up to a definite time t (AUC\[0-t\]), AUC from time zero up to infinity (AUC\[0-inf\]), AUC from time zero up to 6 hours post dose (AUC\[0-6\]), AUC from time zero up to 24 hours post dose (AUC\[0-24\]) were determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Blood samples for pharmacokinetic (PK) analysis of chlorambucil were collected on Day 1 and Day 4 in Cycle 1, and on Day 57 in Cycle 3. In each sampling, blood samples (2 mL/sample) were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. Elimination half-life (t1/2) was determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Blood samples for pharmacokinetic (PK) analysis of chlorambucil were collected on Day 1 and Day 4 in Cycle 1, and on Day 57 in Cycle 3. In each sampling, blood samples (2 mL/sample) were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. Time of maximum serum concentration (tmax) was determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Blood samples for pharmacokinetic (PK) analysis of chlorambucil and its metabolite phenyl acetic acid mustard were collected on Day 1 and Day 4 in Cycle 1, and on Day 1 in Cycle 3. In each sampling, blood samples (2 milliliter \[mL\]/sample) were collected at pre-dose, and 15 minute (min), 30 min, 1 hour (hr), 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. Maximum serum concentration (Cmax), minimum serum concentration (Cmin) were determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Blood samples for PK analysis of chlorambucil and its metabolite phenyl acetic acid mustard were collected on Day 1 and Day 4 in Cycle 1, and on Day 57 in Cycle 3. In each sampling, blood samples (2 mL/sample) were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. AUC from time zero up to a definite time t (AUC\[0-t\]), AUC from time zero up to infinity (AUC\[0-inf\]), AUC from time zero up to 6 hours post dose (AUC\[0-6\]), AUC from time zero up to 24 hours post dose (AUC\[0-24\]) were determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Blood samples for pharmacokinetic (PK) analysis of chlorambucil and its metabolite phenyl acetic acid mustard were collected on Day 1 and Day 4 in Cycle 1, and on Day 57 in Cycle 3. In each sampling, blood samples (2 mL/sample) were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. Elimination half-life (t1/2) was determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

Blood samples for pharmacokinetic (PK) analysis of chlorambucil and its metabolite phenyl acetic acid mustard were collected on Day 1 and Day 4 in Cycle 1, and on Day 57 in Cycle 3. In each sampling, blood samples (2 mL/sample) were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr post dosing. Time of maximum serum concentration (tmax) was determined. Between participants coefficient of variation (%CVb) was calculated according to the following methods: Transformed Data : 100 \* (square root of the exponential \[standard deviation of loge-transformed \]2-1).

GlaxoSmithKline

On-therapy SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.

Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up \[FU\] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 84 and 168 days after the day of PDFU 1 (PDFU 85 and PDFU 169, respectively) to assess survival status, date of next CLL therapy, and type of therapy. In subsequent visits, the participant continued

Chlorambucil 10 mg/m^2

Age, Continuous

Sex: Female, Male

Asian - Japanese Heritage

Race/Ethnicity, Customized

GSK Response Center

IRC with CT Assessed

IRC Assessed

Investigator-Assessed

All Subjects Population: all participants who received at least one dose of investigational product.

Number of Participants With a Best Response of Either Complete Remission (CR), Nodular Partial Remission (nPR), Complete Remission-incomplete (CRi) or Partial Remission (PR), as Assessed by the Investigator, IRC and IRC With CT

Investigator-Assessed, CR

Investigator-Assessed, CRi

Investigator-Assessed, nPR

Investigator-Assessed, PR

Investigator-Assessed, Responders

IRC Assessed, CR

IRC Assessed, CRi

IRC Assessed, nPR

IRC Assessed, PR

IRC Assessed, Responders

IRC with CT Assessed, CR

IRC with CT Assessed, CRi

IRC with CT Assessed, nPR

IRC with CT Assessed, PR

IRC with CT Assessed, Responders

Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT

Investigator Assessed

Progression Free Survival (PFS), as Assessed by the Investigator and the IRC

Overall Survival (OS)

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Time to Response, as Assessed by the IRC

Duration of Response, as Assessed by the IRC

Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy

Cycle 2-Day 29, Improved, n=5

Cycle 2-Day 29, No Change, n=5

Cycle 2-Day 29, Deteriorated, n=5

Cycle 3-Day 57, Improved, n=4

Cycle 3-Day 57, No Change, n=4

Cycle 3-Day 57, Deteriorated, n=4

Cycle 4-Day 85, Improved, n=4

Cycle 4-Day 85, No Change, n=4

Cycle 4-Day 85, Deteriorated, n=4

Cycle 5-Day 113, Improved, n=4

Cycle 5-Day 113, No Change, n=4

Cycle 5-Day 113, Deteriorated, n=4

Cycle 6-Day 141, Improved, n=4

Cycle 6-Day 141, No Change, n=4

Cycle 6-Day 141, Deteriorated, n=4

Cycle 7-Day 169, Improved, n=1

Cycle 7-Day 169, No Change, n=1

Cycle 7-Day 169, Deteriorated, n=1

Cycle 8-Day 197, Improved, n=1

Cycle 8-Day 197, No Change, n=1

Cycle 8-Day 197, Deteriorated, n=1

Cycle 9-Day 225, Improved, n=1

Cycle 9-Day225, No Change, n=1

Cycle 9-Day 225, Deteriorated, n=1

FU 1-PDFU 1, Improved, n=5

FU 1-PDFU 1, No Change, n=5

FU 1-PDFU 1, Deteriorated, n=5

FU 85-PDFU 85, Improved, n=5

FU 85-PDFU 85, No Change, n=5

FU 85-PDFU 85, Deteriorated, n=5

FU 169-PDFU 169, Improved, n=5

FU 169-PDFU 169, No Change, n=5

FU 169-PDFU 169, Deteriorated, n=5

Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

Baseline, With no B-symptom, n=5

Baseline, With at least one B-symptom, n=5

Cycle 2-Day 29, With no B-symptom , n=5

Cycle 2-Day 29, With at least one B-symptom, n=5

Cycle 3-Day 57, With no B-symptom, n=4

Cycle 3-Day 57, With at least one B-symptom, n=4

Cycle 4-Day 85, With no B-symptom, n=4

Cycle 4-Day 85, With at least one B-symptom, n=4

Cycle 5-Day 113, With no B-symptom, n=4

Cycle 5-Day 113, With at least one B-symptom, n=4

Cycle 6-Day 141, With no B-symptom, n=4

Cycle 6-Day 141, With at least one B-symptom, n=4

Cycle 7-Day 169, With no B-symptom, n=1

Cycle 7-Day 169, With at least one B-symptom, n=1

Cycle 8-Day 197, With no B-symptom, n=1

Cycle 8-Day 197, With at least one B-symptom, n=1

Cycle 9-Day 225, With no B-symptom, n=1

Cycle 9-Day 225,With at least one B-symptom, n=1

FU 1-PDFU 1,With no B-symptom, n=5

FU 1-PDFU 1,With at least one B-symptom, n=5

FU 85-PDFU 85,With no B-symptom ,n=5

FU 85-PDFU 85,With at least one B-symptom, n=5

FU 169-PDFU 169, With no B-symptom, n=5

FU 169-PDFU 169, With at least one B-symptom, n=5

Number of Participants With no B-symptoms and With at Least One B-symptom Over Time

Any AE

Any SAE

Number of Participants With Any Adverse Events (AE) or Serious Adverse Events (SAE)

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Number of Participants With Adverse Events by the Indicated Maximum Toxicity Grade

Infection, Grade 3

Infection, Grade 4

Myelosuppression, Grade 3

Myelosuppression, Grade 4

Number of Participants With at Least One Grade 3/Grade 4 Adverse Event of Infection or Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia)

IgA, FU 1-PDFU 1, n=5

IgA, FU 169-PDFU 169, n=4

IgG, FU 1-PDFU 1, n=5

IgG, FU 169-PDFU 169, n=4

IgM, FU 1-PDFU 1, n=4

IgM, FU 169-PDFU 169, n=3

Change From Baseline in the Immunoglobulin(Ig) Antibodies IgA, IgG, and IgM

Number of Participants With Positive Minimal Residual Disease (MRD)

Expression of Beta 2 Microglobulin

Cycle 1-Day 1, n=4

Cycle 4-Day 85, n=4

Expression of Complement CH50

Cmax, Cycle 1-Day 1, n=5

Cmax, Cycle 1-Day 4, n=4

Cmax, Cycle 3-Day 57, n=4

Cmin, Cycle 1-Day 4, n=5

Cmin, Cycle 3-Day 57, n=4

PK Population: all participants who received at least one dose of investigational product and for whom PK data was collected. Only those participants with non-missing values available at the specified time points were analyzed (represented by n=X in the category titles).

Maximum Serum Concentration (Cmax), and Minimum Serum Concentration (Cmin) for Chlorambucil

AUC(0-t), Cycle 1-Day 1, n=5

AUC(0-t),Cycle 1-Day 4, n=4

AUC(0-t), Cycle 3-Day 57, n=4

AUC(0-inf), Cycle 1-Day 1, n=5

AUC(0-inf), Cycle 1-Day 4, n=4

AUC(0-inf), Cycle 3-Day 57, n=4

AUC(0-24), Cycle 1-Day 1, n=5

AUC(0-24), Cycle 1-Day 4, n=4

AUC(0-24), Cycle 3-Day 57, n=4

AUC(0-6), Cycle 1-Day 1, n=5

AUC(0-6), Cycle 1-Day 4, n=4

AUC(0-6), Cycle 3-Day 57, n=4

PK Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the PK Population.

Area Under the Serum Concentration-time (AUC) for Chlorambucil

Spots Global Cancer Trial Database for leukaemia, lymphoblastic