Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Mantle-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Bendamustine Hydrochloride

Rituximab

Lenalidomide

Antineoplastic Agents, Immunological

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Phase I: Maximally tolerable dose of lenalidomide will be determined, starting with 5 mg per day, and up to maximally 25 mg per day. This treatment is given in combination with bendamustine and rituximab.

Phase II: Determination of progression free survival with treatment with lenalidomide (dosing determined in phase I) in combination with bendamustine and rituximab.

lenalidomide, bendamustine, rituximab

lenalidomide: day 1-21, maximum 13 cycles bendamustine: days 1-2, cycle 1-6 rituximab: day1, cycle 1-6

Mats Jerkeman, MD, PhD

Jan Sundberg, RN

In phase I: Establishing maximally tolerated dose of lenalidomide in combination with bendamustine and rituximab.

In phase II: Evaluation of progression free survival with treatment with lenalidomide, bendamustine and rituximab

This trial consists of both a phase I portion and a phase II portion. In phase I, the MTD of lenalidomide is determined, starting with 5 mg/day given up to maximally 25 mg/day. In combination with this treatment, bendamustine and rituximab are given at fixed doses.

The phase I portion follows a sequential dose escalation, 3+3 design. Initially, three subjects are started treatment with dose regimen 1 (5 mg/day). After the third subject completed two cycles of treatment, if no DLT has occured, the next group of three subjects are treated at the next dose level of lenalidomide (10 mg/day). If one of the three initial subjects experiences a DLT, the cohort is expanded to six subjects. If less than two out of the six subjects experiences a DLT, then the next higher dose group is initiated. If two or more subjects experiences a DLT, no higher dose levels will be tested and the MTD dose has been exceeded.

Additional subjects are enrolled at the MTD on the phase II portion of the trial.

The above described treatment with lenalidomide, bendamustine and rituximab are given in 6 cycles, cycle length 22 days. Lenalidomide is given day 1-21, bendamustine day 1-2 and rituximab day 1. During the following maintenance treatment, single treatment with lenalidomide will be given with the same dose of lenalidomide (25 mg/day) for 7 cycles, whether in phase I or phase II portion of the trial.

Lenalidomide, Bendamustine and Rituximab as First-line Therapy for Patients Over 65 Years With Mantle Cell Lymphoma.

Lenalidomide, Bendamustine and Rituximab as First-line Therapy for Patients Over 65 Years With Mantle Cell Lymphoma - a Nordic Lymphoma Group Trial

Mundipharma Pte Ltd.

Celgene

Roche Pharma AG

Lund University Hospital

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Anti-Infective Agents

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Cytarabine

Dexamethasone

Cisplatin

Dexamethasone acetate

Ofatumumab

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Lenalidomide, Bendamustine and Rituximab as First-line Therapy for Patients Over 65 Years With Mantle Cell Lymphoma.	NCT00963534	Mantle Cell Lym...	lenalidomide, b... lenalidomide, b...	65 Years -	Lund University Hospital
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

Spots Global Cancer Trial Database for nordic lymphoma group