Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Bendamustine Hydrochloride

Rituximab

Antineoplastic Agents, Alkylating

Alkylating Agents

Dose of 120 mg/m2 on Day 1 and Day 2 of each treatment cycle (every 21 days). Patients who are continuing to experience clinical benefit at Cycle 6, as assessed by the investigator, may receive up to 2 additional cycles, to a maximum of 8 cycles.

Bendamustine HCl

SUMMARY: This is a multi-center open label study to evaluate the safety and effectiveness of Treanda™ (also known as bendamustine HCl or SDX-105) in patients who have indolent Non-Hodgkin's lymphoma and have relapsed within a defined timeframe after taking rituximab (Rituxan®). Treanda will be given via 60-minute intravenous infusion on days 1 and 2 of every 21-day treatment cycle. Patients will be treated for 6 cycles unless they develop progressive disease or unacceptable toxicity. Those who continue to receive clinical benefit at end of 6 cycles may receive an additional 2 cycles. Following the end of treatment, patients will be followed for up to 2 years until disease progression or start of another anti-cancer therapy.

Safety and Efficacy of Treanda™ (Bendamustine HCl) in Patients With Indolent Non-Hodgkin's Lymphoma (NHL) Who Are Refractory to Rituximab

A Multi-Center Phase III Study to Investigate the Safety and Efficacy of Treanda™ (Bendamustine HCl) in Patients With Indolent Non-Hodgkin's Lymphoma (NHL) Who Are Refractory to Rituximab

Cephalon

Lymphoma, Follicular

Lymphoma, B-Cell

B-cell Lymphoma

Follicular Lymphoma

Pharmaceutical Solutions

Ofatumumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunologic Factors

Up to 8 cycles of bendamustine (90 mg/m2) on Days 1,2 every 21 days with12 doses of ofatumumab (1000 mg, Day 1 q21 days when with bendamustine and q28 days when given as monotherapy)

Up to 8 cycles of bendamustine (120 mg/m2) on Days 1,2 every 21 days

Ofatumumab was a liquid concentrate solution for infusion presented in glass vials containing 50 mL of solution at a concentration of 20 mg/mL to provide 1000 mg per vial. The ofatumumab infusions were prepared in 1000 mL sterile, pyrogen-free 0.9% NaCl to yield a 1 mg/mL ofatumumab concentration infusion.

Bendamustine infusion

Up to 8 cycles of Bendamustine (90 mg/m2 Days 1 and 2, every 21 days) given in combination with 12 doses of ofatumumab (1000 mg). Ofatumumab will be given on day 1 of each cycle of bendamustine as long as patients in Arm A receive bendamustine. Once patients in Arm A complete bendamustine therapy, the remaining doses of ofatumumab will be given monthly until all 12 doses are completed.

Ofatumumab and Bendamustine infusions (Arm A)

Bendamustine (120 mg/m2 Days 1 and 2, every 21 days, up to 8 cycles).

Bendamustine infusion (Arm B)

Novartis Pharmaceuticals

The purpose of this study was to evaluate the safety and efficacy of ofatumumab and bendamustine combination therapy in patients with indolent B-cell NHL that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

Ofatumumab is an anti-CD20 monoclonal antibody shown to have monotherapy activity in patients with follicular lymphoma that has relapsed following rituximab-containing therapy. Bendamustine was approved by FDA for the treatment of in patients with indolent B-cell Non-Hodgkin's Lymphoma (NHL) that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

Biologics have demonstrated enhanced efficacy when added to chemotherapeutic combinations in the frontline treatment for indolent NHL. The combination of ofatumumab and bendamustine may provide additional clinical benefit and efficacy to those who no longer respond to rituximab or rituximab-containing regimens.

The objective of this study is to determine the effect of ofatumumab and bendamustine combination therapy in patients with indolent B-cell NHL that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

randomized open label bendamustine monotherapy vs. ofatumumab

Ofatumumab Bendamustine Combination Compared With Bendamustine Monotherapy in Indolent B-cell NHL Unresponsive to Rituxtherapy

Randomized Open Label of Ofatumumab and Bendamustine Combination Compared With Bendamustine Monotherapy in Indolent B-cell Non-Hodgkin's Lymphoma Unresponsive to Rituximab or a Rituximab-Containing Regimen During or Within Six Months of Treatment

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

PFS is defined as the time interval between randomization until disease progression or death (due to any cause).

ORR: Percentage of subjects achieving complete response (CR) or partial response (PR) from the start of randomization until disease progression or the start of new anti-cancer therapy, including the optional ofatumumab for subjects in Arm B based on responses from the IRC assessment of best overall response using the Revised Response Criteria for Malignant Lymphoma (RRCML). Response criteria is CR, PR, standard disease (SD), progressive disease (PD) or not estimable. CR is the complete disappearance of all detectable clinical evidence of disease \& disease-related symptoms. PR is at least a 50% decrease from baseline in the sum of the product of the diameters (SPD) of target lesions. SD is failure to attain the criteria needed for a CR, PR or PD. PD is the appearance of any new lesion more than 1.5 cm in any axis or at least a 50% increase from nadir in the SPD of target or non target lesions or at least a 50% increase in the longest diameter(SLD) or any Target or non target lesions.

The interval of time between the date of randomization and the date of death due to any cause. For subjects who are alive, time of death will be censored at the date of last contact.

Time to response = time from randomization to the first response (CR/ PR). If no CR/PR value was present data was to be censored at last adequate assessment.

Time (in months) from the initial response (CR/PR) to first documented sign of disease progression or death due to any cause.

Time from randomization until disease progression

Time to next therapy was defined as the time (in months) from randomization date to the date of receiving the next line treatment, including all therapy types.

Time to next therapy was defined as the time (in months) from randomization date to the date of receiving the next line treatment, including all therapy types

The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) is intended as a lymphoma specific additional concerns subscale that is designed to supplement the FACT-G. The subscale consists of 15 items. Subjects respond to the items on a five point Likert scale ranging from 0 'Not at all' to 4 'Very much'. Subscale scores are calculated by summing individual items to obtain a score, then multiplying the sum of the item scores by the number of items in the subscale, then dividing by the number of items answered. The Score range is 0 -28 for Physical Well-Being, Social/Family Well-Being, 0 -24 for Functional Well-Being and 0 - 60 for the Lymphoma subscale (LYMS). FACT lymphoma TOI is the sum of Physical, Functional Well-Being \& Lymphoma scores. FACT-G Total Score is the sum of Physical, Emotional, Social and Functional Well-Being scores. FACT-Lymph is the sum of Physical, Social, Emotional, Functional and Lymphoma scores. The higher the score, the better the QOL. C =cycle; D=Day

The EuroQoL Five-Dimension (EQ-5D) is a self-administered, generic, indirect utility measure used for health economic analysis.EQ-5D should be answered as one of 3 levels about current condition for 5 dimensions and was calculated total average by giving a weighting on 3 level of answers (EQ-5D levels into 'no problems' (level 1) and 'problems' (level 2 and 3)).

Table of scores by each level for EQ-5D items: mobility(level 1=0, level2=0.069,level 3=0.314), self care(level 1=0, level2=0.104,level 3=0.214), usual activities(level 1=0, level2=0.036,level 3=0.094), pain/discomfort (level 1=0, level2=0.,level 3=0.386) and anxiety/depression(level 1=0, level2=0.071,level 3=0.2)

\*EQ-5D Total = 1 - 0.081 - (the score of the each level) - 0.269 (if at least one of level 3 presents)

The Health Change Questionnaire,(HCQ) used is a nine item scale that asks the patient to rate change in status since beginning treatment on this study. For HCQ, values from 1 to 9 were assigned to the 9 responses in the HCQ questionnaire, ranging from 1 for 'my health is a great deal better' to 9 for 'my health is a great deal worse' since the beginning of the study. Lower scores represent better conditions

The Health Change Questionnaire, (HCQ) used is a nine item scale that asks the patient to rate change in status since beginning treatment on this study. For HCQ, values from 1 to 9 were assigned to the 9 responses in the HCQ questionnaire, ranging from 1 for 'my health is a great deal better' to 9 for 'my health is a great deal worse' since the beginning of the study. Lower scores represent better conditions

Tumor size was measured by the mean change in the sum of the products of the greatest diameter (SPD) of the largest abnormal nodes from baseline to post-baseline by CT Scan.

This is the number of participants with change in ECOG status. Change is measured categorically by "Improvement, deterioration and No change". Improvement is defined as decrease from baseline by at least one step on the ECOG performance status scale. Deteriorations is defined as increase from baseline by at least one step on the ECOG performance status scale. ECOG status to evaluate daily living: 0: Fully active, able to carry on all pre-disease performance without restriction; 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4: Completely disabled; cannot carry on any self care.Totally confined to bed or chai; 5: Dead

A summary by responders and non-responders

at scheduled visits for actual values as well as for change from baseline

Concentrations of ofatumumab in plasma listed by actual relative time and summarized by nominal time.

The percent change of CD5+CD19+ and CD5-CD19+ from baseline was summarized to assess the treatment effect, to monitor the normal B-cell population, and to follow their recovery.

The number of participants with positive and negative baseline HACA results

AE: Any sign or symptom that occurs during the study treatment plus up to 60 days post treatment

ofatumumab and bendamustine arm. Participants received up to 8 cycles of bendamustine (90 mg/m2) on Days 1,2 every 21 days with 12 doses of ofatumumab (1000 mg, Day 1 q21 days when with bendamustine and every 28 days

Ofa + Benda (Arm A)

Bendamustine monotherapy. Participants received up to 8 cycles of bendamustine (120 mg/m2 on Days 1, 2 every 21 days

Benda (Arm B)

Eligible benda arm participants who were offered optional ofatumumab following disease progression

Optional Ofa

All participants in the Ofa + Benda arm and in the Benda only arm

Ofa + Benda (Arm A) + Benda (Arm B) + Optional Ofa

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

0 - 2

3 - 5

Missing

Follicular Lymphoma International Prognostic Index-1 (FLIPI) is a prognostic tool that may be used to evaluate \& select treatments based on differences in survival between risk groups. Low: (0 - 1) corresponds to better survival rate; intermediate: 2, corresponds to intermediate survival rate \& high: (\>=3) corresponds to worse survival rate. This index uses parameters related to subject characteristics such as age, tumor burden (Ann Arbor stage, number of nodal sites), tumor aggressiveness (serum Lactate Dehydrogenase (LDH) level), \& consequences of the lymphoma on the host (hemoglobin level).

FLIPI-1 Score at Screening

< (Lower limit of normal (LLN)

>= LLN

LLN - equal to the 5th percentile of a healthy, non-smoking population

Baseline Absolute Lymphocyte Count (ALC)

Fc Gamma Receptor (FcR) Gamma 3A Variation

Negative

Positive

Human Anti-Chimeric Antibodies (HACA)

As the primary endpoint of the study was not met, secondary efficacy endpoints were not fully tested. The data being reported is for information only and not intended to be inferential.

Study Director

ITT: The Intent-to-Treat (ITT) population included subjects who were randomized in the study.

Progression-free Survival (PFS) as Assessed by the Independent Review Committee (IRC)

Subjects in ITT with Follicular Lymphoma (FL). ITT population included subjects who were randomized in the study.

Progression-free Survival (PFS) in Participants With Follicular Lymphoma (FL) Per IRC

ITT: The ITT population included subjects who were randomized in the study.

Overall Response Rate (ORR) in All Participants Per IRC

for Follicular Lymphoma (FL) participants

Subjects in ITT with FL. ITT population included subjects who were randomized in the study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety and Efficacy of Treanda™ (Bendamustine HCl) in Patients With Indolent Non-Hodgkin's Lymphoma (NHL) Who Are Refractory to Rituximab	NCT00139841	Non-Hodgkin's L...	Bendamustine HC...	18 Years -	Teva Branded Pharmaceutical Products R&D, Inc.
Ofatumumab Bendamustine Combination Compared With Bendamustine Monotherapy in Indolent B-cell NHL Unresponsive to Rituxtherapy	NCT01077518	Lymphoma, Folli...	Ofatumumab Bendamustine in... Ofatumumab and ... Bendamustine in...	18 Years -	Novartis

Spots Global Cancer Trial Database for rituximab refractory