Clinical trial NCT01437709: Ofatumumab With or Without Bendamustine for Patients With Mantle Cell Lymphoma Ineligible for Autologous Stem Cell Transplant
Official title: Ofatumumab With or Without Bendamustine for Patients With Mantle Cell Lymphoma Ineligible for Autologous Stem Cell Transplant
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mantle Cell Lymphoma
Keywords: Bendamustine HCL
Ofatumumab (GSK 1841157)
Immunotherapy
Chemoimmunotherapy
11-050
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2011-09-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Single Agent Efficacy (as Determined by Response Rate)
timeFrame: 2 years
measure: the Efficacy (as Determined by Response Rate) of the Combination Ofatumumab + Bendamustine
timeFrame: 2 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 6 years
measure: Progression Free Survival (PFS)
timeFrame: 2 years
measure: Remission Duration
timeFrame: Up to 6 years
measure: Response Duration
timeFrame: Up to 6 years
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center at Basking Ridge
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center @ Suffolk
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering West Harrison
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering Cancer Center at Mercy Medical Center
state: New York
city: Sleepy Hollow
country: United States
facility: Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Paul Hamlin, MD
role: PRINCIPAL_INVESTIGATOR
References: