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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01437709
First received: September 19, 2011
Last updated: November 3, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Mantle Cell Lymphoma
Biological: Ofatumumab (This arm is closed)
Other: Ofatumumab + Bendamustine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Ofatumumab With or Without Bendamustine for Patients With Mantle Cell Lymphoma Ineligible for Autologous Stem Cell Transplant

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • single agent efficacy (as determined by response rate) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    in high risk patients. Assessments prior to each cycle of immunotherapy or chemoimmunotherapy: (every 4 weeks)


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    will be analyzed using Kaplan-Meier estimation, and logrank tests or Cox regression models when covariates are involved.

  • progression free survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    will be analyzed using Kaplan-Meier estimation, and logrank tests or Cox regression models when covariates are involved.

  • Remission duration [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    (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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    (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.


Estimated Enrollment: 44
Study Start Date: September 2011
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: patients receiving Immunotherapy (This arm is closed)
The proposed study is a Simon 2 stage optimal study design investigating the activity of ofatumumab alone or in conjunction with Bendamustine for patients with MCL who are either not candidates for ASCT or aged 65 or older. The study design will allow for an estimation of the single agent response of ofatumumab in patients at low biologic risk for immediate disease progression.
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
Experimental: patients receiving Chemoimmunotherapy
The proposed study is a Simon 2 stage optimal study design investigating the activity of ofatumumab alone or in conjunction with Bendamustine for patients with MCL who are either not candidates for ASCT or aged 65 or older. The combined regimen will assess the response rates of the combined chemo- immunotherapy program in patients with need for cytoreductive therapy, or high risk for disease progression. Patients with a leukemic phase only presentation of mantle cell lymphoma generally have clinically low-risk disease, regardless of mantle cell IPI calculations. Upon reciew with the principal investigator, these patients may be stratified to the immunotherapy only arm if clinically appropriate.
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01437709

Contacts
Contact: Paul Hamlin, MD 212-639-6143
Contact: Andrew Zelenetz, MD, PhD 212-639-2656

Locations
United States, New Jersey
Memorial Sloan Kettering Cancer Center at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Paul Hamlin, MD    212-639-6143      
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Paul Hamlin, MD    212-639-6143      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Paul Hamlin, MD    212-639-6143      
Contact: Andrew Zelenetz, MD, PhD    212-639-2656      
Principal Investigator: Paul Hamlin, MD         
Memorial Sloan Kettering Cancer Center at Mercy Medical Center Recruiting
Rockville Centre, New York, United States, 11570
Contact: Paul Hamlin, MD    212-639-6143      
Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Paul Hamlin, MD    212-639-6143      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
GlaxoSmithKline
Investigators
Principal Investigator: Paul Hamlin, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01437709     History of Changes
Other Study ID Numbers: 11-050
Study First Received: September 19, 2011
Last Updated: November 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Bendamustine HCL
Ofatumumab (GSK 1841157)
Immunotherapy
Chemoimmunotherapy
11-050

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies, Monoclonal
Bendamustine
Nitrogen Mustard Compounds
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014