A Phase 2 interventional study of Bendamustine and Rituximab in Diffuse Large B-Cell Lymphoma, Lymphoma, Diffuse Large-Cell and Diffuse Large-Cell Lymphoma, sponsored by UNC Lineberger Comprehensive Cancer Center. Completed at 7 sites in United States. Open to participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2017-05-24.
Sponsored by UNC Lineberger Comprehensive Cancer Center · Phase 2, Interventional, and Treatment
The purpose of this research study is to learn about the safety of the treatment with a combination of bendamustine and rituximab and to find out what effects, both good and bad this treatment has on DLBCL. In addition to learning about the combination of bendamustine and rituximab, the researchers are interested in learning about how this cancer treatment affects daily activities. Subjects will be asked to complete a Geriatric Assessment (GA). GAs are designed to gather information on memory, nutritional status, mental health, and level of social support. GAs are also designed to help the health care team understand how well subjects can carry out their day to day activities and to briefly describe what other medical conditions subjects may have. This assessment will help the health care team understand a subject's "functional age" (the age a subject functions at) as compared to a subject's actual age.
The researchers also want to learn how chemotherapy affects the aging process in our bodies. This is done by measuring the amount of p16 in blood. Researchers want to understand if chemotherapy changes the levels of p16 in blood.
This multicenter Phase II clinical study will investigate the complete response (CR) rate after therapy with bendamustine combined with rituximab in older (≥65 years old) patients with previously untreated stage II-IV DLBCL deemed poor candidates for cyclophosphamide, doxorubicin hydrochloride, vincristine (Oncovin®), prednisone, rituximab (CHOP-R); n=37. The hypothesis being tested is that this regimen will be safe and effective as frontline therapy in older DLBCL patients deemed poor candidates for CHOP-R. After 3 cycles of therapy, patients with less than a partial response (PR) will come off study, and be managed at the discretion of their treating physician. Patients who achieve a PR after 3 cycles will continue for a total of 8 cycles of therapy, while patients who achieve a CR will continue for a total of 6 cycles of therapy. Secondary objectives include overall response rates (ORR), disease-free, progression-free and overall survival, and an evaluation of the toxicity and tolerability of the regimen.
This trial also includes an exploratory analysis designed to evaluate a potential correlation between expression of the senescence marker p16INK4a and the toxicity associated with this regimen.
In addition, patients will be asked to participate in a Geriatric Assessment (GA) tool during the trial.
5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's enrollment of 23 is below the median of 40 across 4,508 interventional studies indexed under Lymphoma.
Browse Lymphoma studies →UNC Lineberger Comprehensive Cancer Center is the lead sponsor of 414 studies on the registry; 96 are open to participants now.
Of its 32 completed or terminated interventional studies of FDA-regulated products, 25 (78%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
This is a single arm intervention where patients will receive bendamustine at a dose of 120 mg/m\^2 infused over 60 minutes in days 1 and 2 of each 21 day cycle along with rituximab 375 mg/m\^2 after bendamustine on day 1 of each cycle. Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 3 at baseline were allowed to receive bendamustine at a dose of 90 mg/m\^2 daily with a dose increase to 120 mg/m\^2 daily if their ECOG improved.
Drug: Bendamustine · Drug: Rituximab
Dosage Form: Intravenous (60 minute infusion) Dosage: 120mg/m2 (ECOG = 0-2) or 90mg/m2 (ECOG = 3) Frequency: Day 1 and Day 2; Every 3 weeks of a 21 day cycle. Duration: 3-6 Cycles
Also known as: TREANDA, BENDAMUSTINE HYDROCHLORIDE, (NDA) 022249
Dosage form: Intravenous Dosage: 375 mg/m2 Frequency: Day 1 of every 3 weeks of a 21 day Cycle Duration: 3-6 Cycles
Also known as: Rituxan, (BLA) 103705
Complete Response (CR) Rate as Defined by The International Harmonization Project for Response Criteria
Complete response (CR) is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. The complete response rate is the percentage of participants achieving a CR.
Time frame: 2 years
Overall Response Rate (ORR)
The ORR consists of the complete response rate + the partial response rate (percentage of participants achieving a complete or partial response). Complete response is defined by The International Harmonization Project for Response Criteria as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Partial response is defined as regression of measurable disease and no new sites.
Time frame: 2 years
Partial Response Rate
The percentage of participants achieving a partial response (PR). PR is defined by The International Harmonization Project for Response Criteria as regression of measurable disease and no new sites.
Time frame: 2 years
Estimate of Progression-Free Survival
Progression-free survival (PFS) will be summarized using the Kaplan-Meier method. PFS was defined as the time from the start of treatment until lymphoma progression or death as a result of any cause. Progression was defined by The International Harmonization Project for Response Criteria as any new lesion or increase by ≥50% of previously involved sites from nadir.
Time frame: 2 years with the median follow-up of 29 months
Overall Survival
This represents the Kaplan-Meier estimates of median overall survival defined as the time from start of treatment until death as a result of any cause.
Time frame: 2 years with the median follow-up of 29 months
Evaluate the Toxicity and Tolerability of Bendamustine in Combination With Rituximab
The major grade 3 or higher adverse events were haematological toxicities. The results below include common haematological and non-haematological toxicities of grade 3 or higher. A complete record of all adverse events are reported in the adverse events section. National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0 were used to assess toxicity.
Time frame: Adverse events were collected while patients were on active treatment. The median treatment time was 18 weeks.
23 patients were enrolled between March 2011 and May 2013.
| Milestone | Bendamustine, Rituximab |
|---|---|
| Started | 23 |
| Completed | 11 |
| Not completed | 12 |
| Withdrew: Adverse event | 3 |
| Withdrew: Death | 2 |
| Withdrew: Withdrawal by subject | 2 |
| Withdrew: Disease progression | 2 |
| Withdrew: Clinical deterioration | 1 |
| Withdrew: Physician decision | 1 |
| Withdrew: Other complicating disease (stroke) | 1 |
Complete response (CR) is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. The complete response rate is the percentage of participants achieving a CR.
| percentage of participants | Bendamustine, Rituximab |
|---|---|
| Complete Response (CR) Rate as Defined by The International Harmonization Project for Response Criteria | 52 (30.6 to 73.2) |
The ORR consists of the complete response rate + the partial response rate (percentage of participants achieving a complete or partial response). Complete response is defined by The International Harmonization Project for Response Criteria as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Partial response is defined as regression of measurable disease and no new sites.
| percentage of participants | Bendamustine, Rituximab |
|---|---|
| Overall Response Rate (ORR) | 78 |
The percentage of participants achieving a partial response (PR). PR is defined by The International Harmonization Project for Response Criteria as regression of measurable disease and no new sites.
| percentage of participants | Bendamustine, Rituximab |
|---|---|
| Partial Response Rate | 26 (10.2 to 48.4) |
Progression-free survival (PFS) will be summarized using the Kaplan-Meier method. PFS was defined as the time from the start of treatment until lymphoma progression or death as a result of any cause. Progression was defined by The International Harmonization Project for Response Criteria as any new lesion or increase by ≥50% of previously involved sites from nadir.
| Months | Bendamustine, Rituximab |
|---|---|
| Estimate of Progression-Free Survival | 5.4 (3.8 to 10.2) |
This represents the Kaplan-Meier estimates of median overall survival defined as the time from start of treatment until death as a result of any cause.
| Months | Bendamustine, Rituximab |
|---|---|
| Overall Survival | 10.2 (3.8 to 13.3) |
The major grade 3 or higher adverse events were haematological toxicities. The results below include common haematological and non-haematological toxicities of grade 3 or higher. A complete record of all adverse events are reported in the adverse events section. National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0 were used to assess toxicity.
| percentage of patients | Bendamustine, Rituximab |
|---|---|
| Lymphopenia | 70 |
| Anemia | 26 |
| Neutropenia | 17 |
| Thrombocytopenia | 17 |
| Lymphocytosis | 4 |
| Fatigue | 13 |
| Anorexia | 9 |
| Hyperglycemia | 9 |
| Urinary Tract Infection | 9 |
| Arthralgia | 4 |
| Atrial Fibrillation | 4 |
| Cognitive Disturbance | 4 |
| Generalized Muscle Weakness | 4 |
| Heart Failure | 4 |
| Hypoalbuminemia | 4 |
| Hyponatremia | 4 |
| Infusion Related Reaction | 4 |
| Myalgia | 4 |
| Nausea | 4 |
| Pleural Effusion | 4 |
| Maculopapular Rash | 4 |
| Sepsis | 4 |
| Skin Infection | 4 |
Collected over Adverse events were collected while patients were on active treatment. The median treatment time was 18 weeks.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Bendamustine, Rituximab | 17/23 (73.9%) | 15/23 (65.2%) | 23/23 (100%) |
| Event | Bendamustine, Rituximab |
|---|---|
| Urinary tract infectionInfections and infestations | 3/23 |
| AnorexiaMetabolism and nutrition disorders | 2/23 |
| Neutrophil count decreasedInvestigations | 2/23 |
| Platelet count decreasedInvestigations | 2/23 |
| SepsisInfections and infestations | 2/23 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 2/23 |
| FeverGeneral disorders | 2/23 |
| Death NOSGeneral disorders | 1/23 |
| Heart failureCardiac disorders | 1/23 |
| HyponatremiaMetabolism and nutrition disorders | 1/23 |
| Event | Bendamustine, Rituximab |
|---|---|
| AnemiaBlood and lymphatic system disorders | 20/23 |
| FatigueGeneral disorders | 20/23 |
| HypoalbuminemiaMetabolism and nutrition disorders | 19/23 |
| Lymphocyte count decreasedInvestigations | 17/23 |
| Platelet count decreasedInvestigations | 15/23 |
| AnorexiaMetabolism and nutrition disorders | 14/23 |
| Aspartate aminotransferase increasedInvestigations | 14/23 |
| White blood cell decreasedInvestigations | 14/23 |
| Alkaline phosphatase increasedInvestigations | 13/23 |
| NauseaGastrointestinal disorders | 11/23 |
| Age, Continuous(years) | Bendamustine, Rituximab |
|---|---|
| Median | 80 (65 to 89) |
| Sex: Female, Male(Participants) | Bendamustine, Rituximab |
|---|---|
| Female | 11 |
| Male | 12 |
| Race (NIH/OMB)(Participants) | Bendamustine, Rituximab |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 2 |
| White | 21 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Bendamustine, Rituximab |
|---|---|
| United States | 23 |
| Stage(Participants) | Bendamustine, Rituximab |
|---|---|
| II | 4 |
| III | 7 |
| IV | 12 |
| ECOG Performance Status(Participants) | Bendamustine, Rituximab |
|---|---|
| 0 | 2 |
| 1 | 9 |
| 2 | 6 |
| 3 | 6 |
| International Prognostic Index (IPI)(Participants) | Bendamustine, Rituximab |
|---|---|
| 2 | 5 |
| 3 | 5 |
| 4 | 8 |
| 5 | 5 |
| Lactate Dehydrogenase (LDH)(Participants) | Bendamustine, Rituximab |
|---|---|
| Normal | 8 |
| Elevated | 15 |
1 further baseline measures are reported on the registry.
This study is completed, as verified in Apr 2017. You cannot join it, but the record below documents what was studied.
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