Phase I/II Trial of Dexamethasone, Ofatumumab and Bendamustine [Treanda] (DOT) as First-line Treatment of Mantle-cell Lymphoma (MCL) in the Elderly
1. Age ≥ 60 years.
2. ECOG Performance Status 0-1.
3. Life expectancy of at least 6 months.
4. Histological diagnosis of MCL (morphology, CD5+/CD20+ /CD23-, t(11:14) and/or cyclin
5. Disease requiring treatment (patients with bone marrow only disease, who are
candidates for a watch-and-wait approach, will be excluded)
6. Adequate bone marrow, liver and renal function, unless the abnormality is related to
the tumor and is unlikely to affect the safety of bendamustine and ofatumumab use.
Adequate marrow and organ function will be assessed by the following laboratory
requirements to be conducted within 7 days prior to screening:
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count (ANC) ≥ 1000/µl
- Platelet count ≥ 75000/µl
- Total bilirubin ≤ 1.5 times the ULN
- AST and ALT ≤ 2.5 x ULN
- Alkaline phosphatase ≤ 4 x ULN
- Serum creatinine ≤ 2.5 x ULN
7. PT-INR/PTT < 1.5 x ULN [Patients who are being therapeutically anticoagulated with
agent such as coumadin or heparin will be allowed to participate provided that no
prior evidence of underlying abnormality in these parameters exists]
8. Written informed consent.
1. Previous treatment for mantle-cell lymphoma (MCL)
2. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or
antiviral treatment such as, but not limited to, chronic renal infection, chronic
chest infection with bronchiectasis, tuberculosis and active Hepatitis C.
3. Other past or current malignancy. Subjects who have been free of malignancy for at
least 5 years, or have a history of completely resected non-melanoma skin cancer, or
successfully treated in situ carcinoma are eligible.
4. Clinically significant cardiac disease including unstable angina, acute myocardial
infarction within 6 months prior to Visit 1, congestive heart failure, and arrhythmia
requiring therapy, with the exception of extra systoles or minor conduction
5. History of significant cerebrovascular disease or event with significant symptoms or
6. Glucocorticoid use, unless given in doses ≤ 100 mg/day hydrocortisone (or equivalent
dose of other glucocorticoid) for <7 days for exacerbations other than CLL (e.g.,
7. Known HIV positive
8. Subjects who have current active hepatic or biliary disease (with exception of
patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable
chronic liver disease per investigator assessment).
9. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In
addition, if negative for HBsAg but HBcAb positive and HBsAb negative, a HB DNA test
will be performed and if positive the subject will be excluded. Note: If HBcAb
positive and HBsAb positive, which is indicative of a past infection, the subject can
10. Positive serology for hepatitis C (HC) defined by positive test for HCAb, in which
case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the
11. Treatment with any known non-marketed drug substance or experimental therapy within 5
terminal half lives or 4 weeks prior to Visit 1, whichever is longer or currently
participating in any other interventional clinical study
12. Known or suspected inability to comply with study protocol
13. History of organ allograft
14. Patients with evidence or history of bleeding diathesis.
15. Patients undergoing renal dialysis.
16. Substance abuse, medical psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results.
17. Any condition that is unstable or could jeopardize the safety of the patient and
their compliance in the study.