Mantle Cell Lymphoma
Conditions
Keywords
Bendamustine HCL, Ofatumumab (GSK 1841157), Immunotherapy, Chemoimmunotherapy, 11-050
Brief summary
This study is being done to understand how to treat Mantle Cell Lymphoma (MCL). The goals of treatment are to control the lymphoma with the least amount of side effects. In many cases, MCL is treated with an antibody plus chemotherapy. An antibody is a laboratory-produced substance created to attach to proteins on the cancer cells, eventually destroying them. Chemotherapy is medicine that specifically destroys cancer cells. The purpose of this study is to find out what effects, good and/or bad, the drugs Ofatumumab and Bendamustine have on this type of cancer. Patients in this study will either receive Ofatumumab alone, or Ofatumumab combined with Bendamustine.
Interventions
BIOLOGICALOfatumumab (This arm is closed)
Ofatumumab Day 1 Week 1: 1000 mg, Day 2 week 1: 1000mg. Patients who exhibit a baseline leukocytosis ≥ 20,000 will receive 300 mg of ofatumumab on day 1, week 1. Thereafter, they can receive the 1000 mg dose Ofatumumab Day 1, Weeks 2-4: 1000 mg Will reassess 8-10 weeks after conclusion of treatment with CT CAP, and following this q 12 wks for 2 yrs, then q 6mo until POD or for a maximum of 5 years
Ofatumumab day 1 + Bendamustine 90 mg/m2 days 1 & 2 x 6 cycles q 28 days Cycle 1, day 1: Ofatumumab 1000 mg followed by Bendamustine 90 mg/m2. Patients who exhibit a leukocytosis ≥ 20,000 will receive 300 mg of ofatumumab on day 1, week 1. Thereafter, they can receive the 1000 mg dose. Cycle 1, day 2: Ofatumumab 1000mg followed by Bendamustine 90 mg/m2 Cycles 2-6: Ofatumumab 1000 mg day 1, Bendamustine 90 mg/m2 days 1 and 2 Will reassess 4-6 weeks after conclusion of treatment with CT CAP, and following this q 12 wks for 2 yrs, then q 6mo until POD or for a maximum of 5 years
Sponsors
GlaxoSmithKline
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Untreated, non-transplant eligible, newly diagnosed mantle cell lymphoma with measurable disease as determined by CT, and bone marrow biopsy. * Age \> or = to 65 years or \> 18 year and ineligible for HDT/ASCT. * Subjects must not be candidates for intensive high-dose chemotherapy, with or without an autologous stem cell transplant (ASCT), due to one or more of the following factors: * Age ≥ 65 years * Patients \<65 years of age must be ineligible for HDT/ASCT on the basis of comorbidity, organ dysfunction or patient refusal for HDT/ASCT Comorbid disease, such as CAD, CHF, pulmonary dysfunction, liver or kidney dysfunction, precluding high dose therapy secondary to expected increased morbidity and mortality. * poor performance status (KPS 70% or less) * Ejection fraction \<45% * Impaired pulmonary function test with DLCO \<50% expected * Patient refusal * Medical conditions which in the opinion of the treating physician and DMT preclude HDT/ASCT. * Patients must have a serum creatinine clearance ≥ 40 mL/min (as per the Jelliffe method) or by 12-hour or 24-hour urine creatinine clearance. * Patients must have ANC\>1,000/mcl and Platelets\>100,000/mcl (unless secondary to MCL). * Patients must have a bilirubin level of \< 2.0 mg/dl in the absence of a history of Gilbert's disease (or pattern consistent with Gilbert's). * Negative serologies for Hepatitis B (HB) defined as a negative test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if negative, patient may be included but must undergo HBV DNA PCR testing at the beginning of treatment and throughout treatment duration, at least every 2 months. In addition patients will require treatment with Entacavir .5mg po qday per MSKCC institutional guidelines. * No active co-morbid cardiac condition such as active CHF or CAD. * KPS performance ≥ 70%. * Histologically confirmed mantle cell lymphoma classified according to WHO criteria confirmed at MSKCC. * No prior treatment for mantle cell lymphoma with the exception of corticosteroids for 7 days or less or 1 course of involved-field radiation. * No prior malignancies within 5 yrs, unless treated early stage breast cancer, treated carcinoma in situ of the cervix, resected skin malignancies, or treated prostate cancer. * Women who are pre-menopausal must have a negative serum pregnancy test. Subjects must agree to use appropriate contraception until 4 weeks after the completion of chemotherapy. * Patients must be HIV negative, and have negative serologies for Hepatitis C.
Exclusion criteria
* Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, hepatic involvement by MCL, or stable chronic liver disease per investigator assessment). * Known pregnancy or breast-feeding. * Medical illness unrelated to MCL within the prior one month that will preclude administration of chemotherapy safely. This includes patients with uncontrolled infection, chronic renal insufficiency, myocardial infarction within the past 6 months, unstable angina, active congestive heart failure, cardiac arrhythmias other than chronic atrial fibrillation and chronic active or persistent hepatitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Single Agent Efficacy (as Determined by Response Rate) | 2 years | of the monoclonal antibody ofatumumab alone in low risk patients. Assessments prior to each cycle of immunotherapy or chemoimmunotherapy: (every 4 weeks) |
| the Efficacy (as Determined by Response Rate) of the Combination Ofatumumab + Bendamustine | 2 years | in high risk patients. Assessments prior to each cycle of immunotherapy or chemoimmunotherapy: (every 4 weeks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 6 years | will be analyzed using Kaplan-Meier estimation, and logrank tests or Cox regression models when covariates are involved. |
| Progression Free Survival (PFS) | 2 years | will be analyzed using Kaplan-Meier estimation, and logrank tests or Cox regression models when covariates are involved. |
| Remission Duration | Up to 6 years | (calculated from confirmation of CR to progression)will be analyzed using competing risks tools (with death as a competing risk for progression), and will be done on the subsets of patients who have CR or CR/PR. |
| Response Duration | Up to 6 years | (calculated from confirmation of response (CR/PR) to progression. will be analyzed using competing risks tools (with death as a competing risk for progression), and will be done on the subsets of patients who have CR or CR/PR. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ofatumumab Ofatumumab alone for patients with MCL who are either not candidates for ASCT or aged 65 or older. | 3 |
| Ofatumumab + Bendamustine Ofatumumab + Bendamustine for patients with MCL who are either not candidates for ASCT or aged 65 or older. | 24 |
| Ofatumumab Progressors Ofatumumab alone participants who progressed and then received Ofatumumab + Bendamustine | 3 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Pt trasnferred care | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Ofatumumab | Total | Ofatumumab Progressors | Ofatumumab + Bendamustine |
|---|---|---|---|---|
| Age, Continuous | 55 years | 73 years | 71 years | 73 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 26 Participants | 3 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 3 Participants | 24 Participants | 3 Participants | 18 Participants |
| Region of Enrollment United States | 3 Participants | 30 Participants | 3 Participants | 24 Participants |
| Sex: Female, Male Female | 0 Participants | 5 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 25 Participants | 2 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 13 / 24 | 2 / 3 |
| other Total, other adverse events | 1 / 3 | 23 / 24 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 7 / 24 | 1 / 3 |
Outcome results
Primary
Single Agent Efficacy (as Determined by Response Rate)
of the monoclonal antibody ofatumumab alone in low risk patients. Assessments prior to each cycle of immunotherapy or chemoimmunotherapy: (every 4 weeks)
Time frame: 2 years
Population: Dual therapy arm not assessed
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ofatumumab | Single Agent Efficacy (as Determined by Response Rate) | Complete Response | 1 Participants |
| Ofatumumab | Single Agent Efficacy (as Determined by Response Rate) | No Response | 2 Participants |
Primary
the Efficacy (as Determined by Response Rate) of the Combination Ofatumumab + Bendamustine
in high risk patients. Assessments prior to each cycle of immunotherapy or chemoimmunotherapy: (every 4 weeks)
Time frame: 2 years
Population: Single therapy arm not assessed
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ofatumumab + Bendamustine | the Efficacy (as Determined by Response Rate) of the Combination Ofatumumab + Bendamustine | Complete Response | 16 Participants |
| Ofatumumab + Bendamustine | the Efficacy (as Determined by Response Rate) of the Combination Ofatumumab + Bendamustine | No Response | 8 Participants |
| Ofatumumab Progressors | the Efficacy (as Determined by Response Rate) of the Combination Ofatumumab + Bendamustine | Complete Response | 2 Participants |
| Ofatumumab Progressors | the Efficacy (as Determined by Response Rate) of the Combination Ofatumumab + Bendamustine | No Response | 1 Participants |
Secondary
Overall Survival (OS)
will be analyzed using Kaplan-Meier estimation, and logrank tests or Cox regression models when covariates are involved.
Time frame: Up to 6 years
Population: Participants in Ofatumab Progressors group were included in overall survival calculations for both ofatumumab single-agent and ofatumumab + bendamustine chemotherapy groups because this group consists of participants who were originally assigned to the single treatment arm who then progressed and then received dual therapy treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ofatumumab | Overall Survival (OS) | 2.2 years |
| Ofatumumab + Bendamustine | Overall Survival (OS) | 5.8 years |
Secondary
Progression Free Survival (PFS)
will be analyzed using Kaplan-Meier estimation, and logrank tests or Cox regression models when covariates are involved.
Time frame: 2 years
Population: Participants in Ofatumab Progressors group were included in overall survival calculations for both ofatumumab single-agent and ofatumumab + bendamustine chemotherapy groups because this group consists of participants who were originally assigned to the single treatment arm who then progressed and then received dual therapy treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ofatumumab | Progression Free Survival (PFS) | 0.31 years |
| Ofatumumab + Bendamustine | Progression Free Survival (PFS) | 2.0 years |
Secondary
Remission Duration
(calculated from confirmation of CR to progression)will be analyzed using competing risks tools (with death as a competing risk for progression), and will be done on the subsets of patients who have CR or CR/PR.
Time frame: Up to 6 years
Population: Only participants considered responders were assessed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ofatumumab | Remission Duration | 3.36 years |
| Ofatumumab + Bendamustine | Remission Duration | 1.46 years |
| Ofatumumab Progressors | Remission Duration | 2.45 years |
Secondary
Response Duration
(calculated from confirmation of response (CR/PR) to progression. will be analyzed using competing risks tools (with death as a competing risk for progression), and will be done on the subsets of patients who have CR or CR/PR.
Time frame: Up to 6 years
Population: Only participants considered responders were assessed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ofatumumab | Response Duration | 4.19 years |
| Ofatumumab + Bendamustine | Response Duration | 1.67 years |
| Ofatumumab Progressors | Response Duration | 2.79 years |