Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Cytarabine

Dexamethasone

Rituximab

Cisplatin

Dexamethasone acetate

Ofatumumab

Antineoplastic Agents, Immunological

Immunologic Factors

This study is a parallel arm study, with ofatumumab + DHAP. The Investigators are required to prospectively choose to treat all of their subjects with either DHAP chemotherapy regimens in combination with ofatumumab. All subjects will receive the same ofatumumab regimen and dose.

This study is a parallel arm study, with rituximab + DHAP. The Investigators are required to prospectively choose to treat all of their subjects with either DHAP chemotherapy regimens in combination with rituximab. All subjects will receive the same rituximab regimen and dose.

3 cycles of treatment will be administered. Each cycle will last 21 days. ofatumumab dose: cycle 1, day 1 - 1000 mg; cycle 1, day 8 - 1000 mg; cycle 2, day 1 and cycle 3, day 1 - 1000 mg. DHAP regimen: dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m2/24hrs continuous on day 1 of dosing cycle; cytarabine - 2g/m2 q12 hrs (2 doses) on day 2 of dosing cycle.

OFATUMUMAB + DHAP

3 cycles of treatment will be administered. Each cycle will last 21 days. rituximab dose: cycle 1, day 1 - 375 mg/m2; cycle 1, day 8 - 375 mg/m2; cycle 2, day 1 and cycle 3, day 1 - 375 mg/m2. DHAP regimen: dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m2/24hrs continuous on day 1 of dosing cycle; cytarabine - 2g/m2 q12 hrs (2 doses) on day 2 of dosing cycle.

RITUXIMAB + DHAP

GSK Clinical Trials

This study is being conducted to compare the efficacy and safety of ofatumumab in addition to salvage chemotherapy versus rituximab in addition to salvage chemotherapy in CD20 positive DLBCL subjects relapsing, or with persistent disease, after first-line treatment with rituximab combined with an anthracycline-based chemotherapy regimen and be eligible for ASCT.

As rituximab-based regimens have become standard first-line treatment in CD20 positive DLBCL, the efficacy of rituximab combined with salvage chemotherapy in the second-line setting has decreased and there is a need for new therapies in patients progressing or relapsing after first-line rituximab-based therapy. Replacement of rituximab with ofatumumab in the second-line setting, following progression/relapse after first-line rituximab-containing regimens, offers the potential to overcome relative or complete rituximab resistance and thus improve response rates, the ability to proceed to consolidative HDT/ASCT, and overall survival.

Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma

Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant (ASCT) in Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)

Progression-free survival is defined as the interval of time from the randomization date until the date of stable disease (SD; failure to attain the criteria needed for a CR or PR and no fulfillment of the criteria for progressive disease \[PD\]) after two cycles of salvage chemotherapy, progression, or death, whichever occurs first. Disease progression was based on the assessments of independent reviewers for the disease under study. Disease progression was based on imaging data via the Revised Response Criteria for Malignant Lymphoma (RRCML).

OR is defined as the number of participants achieving either a complete response (CR) or a partial response (PR). CR is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR is defined as at least a 50% decrease from Baseline in the sum of the product of the diameters of target lesions. RRCML was used to assess CR and PR.

Event-free survival is defined as the time from randomization to progressive disease (PD; disease whose course is growth, or spread of the disease), stable disease (SD; failure to attain the criteria needed for a CR or PR and no fulfillment of the criteria for PD) after completion of 2 cycles of therapy, commencement of a new treatment for diffuse large B cell lymphoma (DLBCL) (e.g., radiotherapy), or death from any cause, whichever occurs first. Disease progression was based on the assessments of independent reviewers for the disease under study. Disease progression was based on imaging data via the Revised Response Criteria for Malignant Lymphoma (RRCML).

OS is defined as the time from randomization to death due to any cause. Participants who were still alive by the end of the study were censored.

Stem cell mobilization is the process of stimulating the hematopoietic stem cells (CD34+) to move out of the bone marrow and into the bloodstream, where they can be collected via a process called apheresis. Successful mobilization is defined as the collection of \>2\*10\^6 CD34+ cells/kg. Only those participants, who commenced harvest, following the administration of rituximab or ofatumumab in combination with DHAP combination chemotherapy, were assessed. The number of participants with adequate harvest of CD34+ stem cells (at least 2\*10\^6 CD34+ cells/kg) after dosing of salvage therapy in Cycle 2 and Cycle 3 was analyzed.

The number of participants who completed ASCT is reported.

The FACT-G was developed by the Functional Assessment of Chronic Illness Therapy (FACIT) group for use in adults in a wide range of oncology clinical trial populations. The 27 items of the FACT-G are scored in the following domains: Physical Well-being (7 items), Social/Family Wellbeing (7 items), Emotional Well-being (6 items), and Functional Well-being (7 items). Participants responded to the items on a five-point Likert scale ranging from 0, "Not at all" to 4, "Very much." The total score ranges from 0 to 108; higher scores indicate a better patient-reported outcome/quality of life. Participants were asked to think back over the past week when responding to the items.

The FACT-Lym TOI is a measure that combines the FACT-Lym subscale (15 items; responses to each item range from 0, "Not at all" to 4, "Very much") with two domains taken from the FACT-G (responses to each item range from "Not at all " to "Very much"): Physical Well-being (7 items: lack of energy, nausea, meeting family needs, pain, side effects, feels ill, spends time in bed) and Functional Well-being (7 items: ability to work, work fulfilment, ability to enjoy life, illness acceptance, ability to sleep well, enjoying things done for fun, satisfaction with quality of life). This index is designed to be sensitive to changes in treatment regimens. The total FACT-Lym TOI score ranges from 0 to 116; higher scores indicate a better patient-reported outcome/quality of life. Participants were asked to think back over the past week when responding to the items.

Neutrophil (absolute neutrophil count \[ANC\]) recovery is defined as ANC \>=0.5\*10\^9/Liter and increasing, and platelet (PLT) recovery is defined as PLT \>=10\*10\^9/Liter and increasing. For each cycle, time to ANC recovery is defined as the time from the first dose to the first ANC \>=0.5\*10\^9/Liter and increasing after the nadir in the cycle. For each cycle, time to PLT recovery is defined as the time from the first dose to the first PLT \>=10\*10\^9/L and increasing after the nadir in the cycle.

Engraftment is defined as 1) three consecutive days when the ANC is ≥0.5x109/L and 2) an unsupported platelet count of ≥20x109/L, and the engraftment date is the date that this occurs. If engraftment was not achieved by Day 42 or the last observation, engraftment was deemed to be a failure, and censoring took place at Day 42 or at the last observation.

GlaxoSmithKline

Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of study drug.

Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin \[DHAP\]) or the DVD regimen (DHAP-VIM \[etoposide, ifosfamide, mesna, methotrexate\]-DHAP). Rituximab (375 milligrams per meters squared \[mg/m\^2\]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m\^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m\^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m\^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m\^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram \[kg\] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m\^2 IV on Days 1 and 5).

Rituximab + Chemotherapy

Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter \[mL\]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/\[m\^2\]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m\^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m\^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m\^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m\^2 IV on Days 1 and 5).

Ofatumumab + Chemotherapy

Total

Age, Continuous

Sex: Female, Male

African American/African Heritage

American Indian or Alaska Native

Asian - Central/South Asian Heritage

Asian - East Asian Heritage

Asian - Japanese Heritage

Asian - South East Asian Heritage

Asian - Mixed Race

White - Arabic/North African Heritage

White - White/Caucasian/European Heritage

Missing

Race/Ethnicity, Customized

0 or 1

2 or 3

The secondary age adjusted international prognostic index (SaaIPI) is assessed according to the absence or presence of 3 risk factors (RFs) at the start of Screening: Eastern Cooperative Oncology Group performance status greater than 1, lactate dehydrogenase level greater than the upper level of normal, and Ann Arbor stage II or IV disease. The presence of 0, 1, or more than 1 RFs corresponds to a SaaIPI score reflecting low, intermediate, and high risk of disease progression.

Number of participants with the indicated SaaIPI scores

Late relapsers

Early relapsers/Refractory

Late relapsers are those participants with a complete response (CR: complete disappearance of all detectable clinical evidence of disease/disease-related symptoms) following first line treatment which lasts \>12 months from diagnosis. Early relapsers/refractory are those participants with a CR \<= 12 months, PR (\>=50% decrease from Baseline in the sum of the product of the diameters of target lesions), SD (failure to attain CR or PR; no fulfillment of PD), or PD (disease that has grown or spread) after first-line treatment.

Number of participants in the indicated categories per best response to first-line treatment

GSK Response Center

Intent-to-Treat (ITT) Population: all participants who were randomized and commenced study therapy (at least one dose of a study drug)

Progression-free Survival as Assessed by Independent Reviewers

Independent reviewer-assessed OR

Independent reviewer-assessed CR

Number of Participants With Overall Response (OR) and Complete Response (CR) After Salvage Chemoimmunotherapy

ITT Population. Only participants completing HDT/ASCT are included.

Number of Participants With Overall Response (OR) and Complete Response (CR) Three Months After Autologous Stem Cell Transplant

Event-free Survival

Overall Survival (OS)

ITT Population. Only participants commencing leukapheresis are included.

Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram From Peripheral Blood

Number of Participants Completing Autologous Stem Cell Transplant (ASCT)

ITT Population. Only those participants who provided data were assessed.

Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) During Treatment

Change From Baseline in the Functional Assessment of Cancer Therapy Lymphoma Trial Outcome Index (FACT-Lym TOI) Total Score During Treatment

Statistics are presented for Category-Neutrophils, Cycle 1. Confidence Interval (CI) estimated using the Brookmeyer-Crowley method. HR are estimated using the Pike estimator. A hazard ratio \<1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.

Statistics are presented for Category-Neutrophils, Cycle 2. Confidence Interval (CI) estimated using the Brookmeyer-Crowley method. HR are estimated using the Pike estimator. A hazard ratio \<1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.

Statistics are presented for Category-Neutrophils, Cycle 3. Confidence Interval (CI) estimated using the Brookmeyer-Crowley method. HR are estimated using the Pike estimator. A hazard ratio \<1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.

Statistics are presented for Category-Platelets, Cycle 1. Confidence Interval (CI) estimated using the Brookmeyer-Crowley method. HR are estimated using the Pike estimator. A hazard ratio \<1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.

Statistics are presented for Category-Platelets, Cycle 2. Confidence Interval (CI) estimated using the Brookmeyer-Crowley method. HR are estimated using the Pike estimator. A hazard ratio \<1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.

Statistics are presented for Category-Platelets, Cycle 3. Confidence Interval (CI) estimated using the Brookmeyer-Crowley method. HR are estimated using the Pike estimator. A hazard ratio \<1 indicates a lower probability of recovery with Ofatumumab compared to Rituximab. HR was adjusted for stratification factors.

Neutrophils, Cycle 1, n=223, 222

Neutrophils, Cycle 2, n=196, 199

Neutrophils, Cycle 3, n=137, 129

Platelets, Cycle 1, n=223, 222

Platelets, Cycle 2, n=196, 199

Platelets, Cycle 3, n=137, 129

Safety Population. Only those participants available for analysis in the given cycle were assessed.

Time to Neutrophil and Platelet Recovery After Each Cycle of Salvage Chemotherapy

Safety population. Only participants completing HDT/ASCT are included.

Time to Engraftment After High-dose Therapy (HDT)/ASCT

Overall Study

Behaviors and Mental Disorders

Lymphoma, Follicular

Aggression

Follicular Lymphoma

Carboplatin

Etoposide

Ifosfamide

Etoposide phosphate

Isophosphamide mustard

Mesna

Antibodies

Antibodies, Monoclonal

Immunoglobulins

This study is a single arm study, but the Investigators are required to prospectively choose to treat all of their subjects with either ICE or DHAP chemotherapy regimens in combination with ofatumumab. Regardless of whether the subject receives ICE or DHAP chemotherapy, all subjects will receive the same ofatumumab regimen and dose.

3 cycles of treatment will be administered. Each cycle will last 21 days. ofatumumab dose: cycle 1, day 1 - 1000 milligrams (mg); cycle 1, day 8 - 1000 mg; cycle 2, day 1 and cycle 3, day 1 - 1000 mg

ICE regimen:

ifosfamide + mesna - 5 grams (g)/meters squared (m\^2)/24 hours (hrs) continuous on day 2 of dosing cycle; carboplatin - AUC 5 (800 mg maximum) on day 2 of dosing cycle; etoposide - 100 mg/m\^2 on days 1, 2 and 3 of dosing cycle.

ofatumumab + ICE

3 cycles of treatment will be administered. Each cycle will last 21 days. ofatumumab dose: cycle 1, day 1 - 1000 mg; cycle 1, day 8 - 1000 mg; cycle 2, day 1 and cycle 3, day 1 - 1000 mg.

DHAP regimen:

dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m\^2/24 hrs continuous on day 1 of dosing cycle; cytarabine - 2 g/m\^2 q12 hrs (2 doses) on day 2 of dosing cycle.

ofatumumab + DHAP

The purpose of this study is to evaluate the safety and efficacy of ofatumumab used in combination with ifosfamide, carboplatin, etoposide (ICE) or dexamethasone, cytarabine, cisplatin (DHAP) salvage chemotherapy regimens in subjects with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who are eligible for autologous stem cell transplant.

Rituximab combined with anthracycline based chemotherapy is the most common first-line treatment for subjects with diffuse large B cell lymphoma (DLBCL). Subjects requiring second-line therapy will most often receive rituximab in combination with salvage chemotherapy as an induction therapy prior to autologous stem cell transplant. With rituximab being in first-line therapy, the response rates for subjects receiving rituximab plus salvage chemotherapy has significantly decreased. Treatment with ofatumumab may be able to overcome the resistance to rituximab in the second-line setting and offer improved response rates. The objective of this study is to evaluate the overall response rate of ofatumumab in combination with ICE or DHAP chemotherapy prior to autologous stem cell transplant. Additional objectives are to evaluate the complete response rate, ability to mobilize cluster of differentiation (CD)34+ cells, progression-free survival (PFS) and overall survival.

Phase II Study of Ofatumumab Plus Ifosfamide, Carboplatin, Etoposide (ICE) or Dexamethasone, Cytarabine, Cisplatin (DHAP) Chemotherapy Regimen in Relapsed/ Refractory Diffuse Large B Cell Lymphoma (DLBCL)

A Single Arm, Safety and Efficacy Study of Ofatumumab in Combination With ICE or DHAP Chemotherapy in Relapsed or Refractory Aggressive Lymphoma Prior to Autologous Stem Cell Transplantation

Responders with OR included participants with complete response (CR) and partial response (PR). This was based on adequate responses from the investigator assessment after the completion of treatment. CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR: at least a 50% decrease from baseline in the sum of the product of the diameters of target lesions.

CR is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms.

CD34+ cells are a mixture of stem cells and white blood cells of various degrees of maturity. Stem cell mobilization is the process of stimulating the hematopoietic stem cells (CD34+) to move out of the bone marrow and into the bloodstream, where they can be collected via a process called apheresis. Successful mobilization was defined as the collection of \>2x10\^6 CD34+ cells/kg. Only those participants, who commenced mobilization, following the administration of ofatumumab in combination with either ICE or DHAP combination chemotherapy, were assessed.

PFS is defined as the interval of time between the date of treatment start and the earlier of the date of disease progression and the date of death due to any cause. Disease progression was based on the assessments locally by investigators for the disease under study. Disease progression was based on imaging data or clinical assessment data (if radiologic assessment data were not possible or assessment was not performed).

Overall survival is defined as the interval of time between the date of treatment start and the date of death due to any cause. For participants who did not die, time of death was censored at the date of last contact.

AUC is defined as the area under the ofatumumab (Ofa) concentration-time curve as a measure of drug exposure. AUC(0-inf) is AUC from the start of infusion extrapolated to infinite time. Results are reported by first dose group and combined, as appropriate.

AUC(0-tau) is the area under the plasma concentration-time curve from time zero (0) over the dosing interval, tau, and is a measure of drug exposure. Tau is 21 days (504 hours) in this study.

CL is the clearance of drug from plasma, which is defined as the volume of plasma from which drug is removed per unit time.

Cmax is defined as the maximum concentration of drug in plasma samples for the dosing occasion.

Ctrough is defined as the trough plasma concentration, which is the measured concentration at the end of a dosing interval (taken directly before the start of the next infusion).

t1/2 is defined as terminal phase half-life, which is the time required for the amount of the drug in the body to decrease by half.

Vss is the apparent volume of distribution when plasma concentrations are measured under steady state conditions. At steady state, the plasma concentration-time profile of the drug is similar after each dose.

Human anti-human antibodies (HAHA) indicate immune response to the administered human monoclonal antibody in a two-step assay. A positive screening result is confirmed in a second step. Negative Conclusive is subset of Negative and is a negative HAHA test result with an ofatumumab concentration \<200 µg/mL in a pharmacokinetic sample collected at the same time as the HAHA sample. Data are presented when a HAHA sample was collected. WD, withdrawal; FU, follow up.

Neutropenia is defined as an abnormal decrease in the number of neutrophils (type of white blood cell in blood) in the blood. Febrile neutropenia is the development of fever in participants with neutropenia. Pancytopenia is defined as inadequate blood-cell formation by bone marrow, resulting in a lack of all blood-cell types.

Anaemia is defined as a pathological deficiency in the oxygen-carrying component of the blood, measured in unit volume concentrations of hemoglobin, red blood-cell volume, or red blood-cell number. Pancytopenia is defined as inadequate blood-cell formation by bone marrow, resulting in a lack of all blood-cell types.

Thrombocytopenia is defined as an abnormal decrease in the number of platelets in circulatory blood. Pancytopenia is defined as inadequate blood-cell formation by bone marrow, resulting in a lack of all blood-cell types.

Participants received 3 cycles (21 days per each cycle) of ofatumumab combined with salvage chemotherapy. Ofatumumab (1000 milligrams \[mg\]) was intravenously (IV) infused on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the salvage chemotherapy, and then on Day 1 only of Cycles 2 and 3. The DHAP (dexamethasone, cytarabine, cisplatin) regimen (salvage chemotherapy) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/square meter \[m\^2\]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 gram (g)/m\^2 over 3 hours (hr) every 12 hr (2 doses) for each infusion on Day 2 of each cycle.

Ofatumumab + DHAP

Participants received 3 cycles (21 days per each cycle) of ofatumumab combined with salvage chemotherapy. Ofatumumab (1000 mg) was IV infused on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the salvage chemotherapy, and then on Day 1 only of Cycles 2 and 3. The ICE (ifosfamide, carboplatin, etoposide) regimen (salvage chemotherapy) contained: etoposide (100 mg/m\^2/day) administered IV on Days 1, 2, and 3 of each cycle; carboplatin (up to 800 mg) on Day 2 of each cycle; and ifosfamide plus mesna, both at 5 g/m\^2/day as an IV continuous infusion on Day 2 of each cycle.

Ofatumumab + ICE

Participants received 3 cycles (21 days per each cycle) of ofatumumab combined with salvage chemotherapy (either DHAP or ICE). Ofatumumab (1000 mg) was IV infused on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the salvage chemotherapy, and then on Day 1 only of Cycles 2 and 3. DHAP contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m\^2/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m\^2 over 3 hr every 12 hr (2 doses) for each infusion on Day 2 of each cycle. ICE contained: etoposide (100 mg/m\^2/day) administered IV on Days 1, 2, and 3 of each cycle; carboplatin (up to 800 mg) on Day 2 of each cycle; and ifosfamide plus mesna, both at 5 g/m\^2/day as an IV continuous infusion on Day 2 of each cycle.

Total Ofatumumab + Chemotherapy

Age Continuous

Asian-Central/South Asian Heritage

Asian-Japanese/East or South East Asian Heritage

White

The secondary age adjusted international prognostic index (SaaIPI) is assessed according to the absence or presence of 3 risk factors (RFs) at the start of Screening: Eastern Cooperative Oncology Group performance status greater than 1, lactate dehydrogenase level greater than the upper level of normal, and Ann Arbor stage II or IV disease. The presence of 0, 1, and 2/ 3 RFs corresponds to an SaaIPI score reflecting low, intermediate, and high risk of disease.

Number of participants with the indicated number of risk factors

Late relapsers are those participants with a complete response (CR) \>12 months after adequate R-CHOP-like first-line treatment. Early relapsers are those participants with a CR \<= 12 months and \>=28 days prior to study treatment after adequate first-line treatment. Refractory participants are those with a CR \<28 days, partial response, stable disease, or progressive disease following first-line treatment.

Number of participants in the indicated categories per best response to first line treatment

Per protocol (PP) Population: all participants who received at least one dose of ofatumumab. Participants with major protocol deviations that could have impacted the efficacy outcome, and participants not exposed to ofatumumab or without CD20+ aggressive lymphoma were excluded from assessment. CD, cluster of differentiation.

Number of Participants With Overall Response (OR), as Assessed by the Investigator

Number of Participants With CR, as Assessed by the Investigator

Stem Cell Mobilization Population. All participants in the PP Population in whom stem cell mobilization was attempted and CD34+ cell data are available.

Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram (kg) From Peripheral Blood

Progression-free Survival (PFS)

Overall Survival

Cycle 1 Day 1, 300 mg; n=4, 17, 21

Cycle 1 Day 1, 1000 mg; n=22, 18, 40

Cycle 3, 300 mg; n=4, 6, 10

Cycle 3, 1000 mg; n=14, 13, 30

Cycle 3, both doses; n=18, 19, 40

Pharmacokinetic Population: all participants (par.) exposed to ofatumumab from whom a pharmacokinetic sample was obtained and analyzed. Data for par. who switched chemotherapy regimen are not included in the summaries by chemotherapy after the switch but are included in the total summaries. Data are provided for the par. attending each visit.

Area Under the Concentration-time Curve From Time Zero to Infinity, AUC(0-inf), of Ofatumumab at the First Infusion (Cycle 1, Day 1) and the Last Infusion (Cycle 3)

Cycle 3 both doses; n=18, 19, 40

Pharmacokinetic Population. Data for participants who switched chemotherapy regimen are not included in the summaries by chemotherapy after the switch but are included in the total summaries. Data are provided for the number of participants attending each visit. Results are reported by first dose group and combined, as appropriate.

Area Under the Concentration-time Curve During the Dosing Interval (AUC(0-tau)) of Ofatumumab at the Last Infusion (Cycle 3)

Clearance (CL) of Ofatumumab

Cycle 1 Day 8, 300 mg; n=4, 13, 17

Cycle 1 Day 8, 1000 mg; n=21, 18, 39

Cycle 3, 300 mg; n=4, 11, 15

Cycle 3, 1000 mg; n=14, 14, 33

Cycle 3, both doses; n=18, 25, 48

Maximum Plasma Concentration (Cmax) of Ofatumumab at the First Infusion (Cycle 1 Day 1), Second Infusion (Cycle 1 Day 8), and Last Infusion (Cycle 3)

Cycle 1 Day 8, 300 mg; n=4, 15, 19

Cycle 1 Day 8, 1000 mg; n=19, 18, 37

Cycle 2, 300 mg; n=4, 16, 20

Cycle 2, 1000 mg; n=21, 18, 39

Cycle 3, 300 mg; n=4, 13, 17

Cycle 3, 1000 mg; n=18, 18, 40

Cycle 3, both doses; n=22, 31, 57

Trough Plasma Concentration (Ctrough) of Ofatumumab Prior to Second Infusion (Cycle 1 Day 8), Third Infusion (Cycle 2), and Last Infusion (Cycle 3)

Terminal Phase Half-life (t1/2) of Ofatumumab

Volume of Distribution at Steady State (Vss) of Ofatumumab

Positive at Day 1; n=26, 35, 61

Negative at Day 1; n=26, 35, 61

Safety Population. Data are presented for those participants who contributed a sample.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma	NCT01014208	Lymphoma, Large...	OFATUMUMAB + DH... RITUXIMAB + DHA...	18 Years -	GlaxoSmithKline
Phase II Study of Ofatumumab Plus Ifosfamide, Carboplatin, Etoposide (ICE) or Dexamethasone, Cytarabine, Cisplatin (DHAP) Chemotherapy Regimen in Relapsed/ Refractory Diffuse Large B Cell Lymphoma (DLBCL)	NCT00823719	Lymphoma, Large...	ofatumumab + IC... ofatumumab + DH...	18 Years -	GlaxoSmithKline
Phase II Study of Ofatumumab Plus Ifosfamide, Carboplatin, Etoposide (ICE) or Dexamethasone, Cytarabine, Cisplatin (DHAP) Chemotherapy Regimen in Relapsed/ Refractory Diffuse Large B Cell Lymphoma (DLBCL)	NCT00823719	Lymphoma, Large...	ofatumumab + IC... ofatumumab + DH...	18 Years -	GlaxoSmithKline

Spots Global Cancer Trial Database for ofatumumab + dhap