Ofatumumab With or Without Bendamustine for Patients With Mantle Cell Lymphoma Ineligible for Autologous Stem Cell Transplant

Mantle Cell Lymphoma Clinical Trial

Official title:

Ofatumumab With or Without Bendamustine for Patients With Mantle Cell Lymphoma Ineligible for Autologous Stem Cell Transplant

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01437709
• Other study ID #: 11-050
• Status: Completed
• Phase: Phase 2
• Start date: September 2011
• Est. completion date: September 12, 2023

Study information

• Verified date: September 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: September 12, 2023
• Est. primary completion date: September 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

Biological:
• Ofatumumab (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

Other:
• Ofatumumab + Bendamustine
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

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Cancer Center @ Suffolk	Commack	New York
United States	Memorial Sloan Kettering West Harrison	Harrison	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center at Mercy Medical Center	Rockville Centre	New York
United States	Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center	Sleepy Hollow	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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)	2 years
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)	2 years
Secondary	Overall Survival (OS)	will be analyzed using Kaplan-Meier estimation, and logrank tests or Cox regression models when covariates are involved.	2 years
Secondary	progression free survival (PFS)	will be analyzed using Kaplan-Meier estimation, and logrank tests or Cox regression models when covariates are involved.	2 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.	2 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.	2 years

External Links

•   Memorial Sloan Kettering Cancer Center