Dexamethasone, Ofatumumab and Bendamustine (DOT) First-line in Mantle-cell Lymphoma(MCL)

NCT ID: NCT01221103

Last Updated: 2011-09-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2012-06-30

Brief Summary

The rationale for this study design is based on the fact that the maximum tolerated dose (MTD) of single-agent ofatumumab and bendamustine have been previously determined. The choice of the doses for the combination is based on the investigators unpublished clinical experience, as well as inferred from extensive experimental data on the use of other monoclonal antibodies in combination chemotherapy in lymphoma patients. The starting dose of the 2 main component drugs is the MTD of each drug as single agent.

Conditions

Lymphoma, Mantle-Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DOT

Combination of dexamethasone, ofatumumab and bendamustine

Group Type: EXPERIMENTAL

Combination of dexamethasone, ofatumumab and bendamustine

Intervention Type: DRUG

• Ofatumumab (liquid concentrate for infusion in glass vials) infused iv on day 1 at 300 mg during the first cycle, followed by infusions of 1000 mg on day 1 of each subsequent cycle
• Bendamustine (powder dissolved in sterile water) infused iv over 30-60 minutes at the dose of 120 mg/m2 (days 2,3 every 21 days) or 120 mg/m2(days 2,3 every 28) or 90 mg/m2 (days 2,3 every 28 days) depending on toxicity
• Dexamethasone administered i.v. at 40 mg (days 1,2,3,4)

Interventions

Combination of dexamethasone, ofatumumab and bendamustine

• Ofatumumab (liquid concentrate for infusion in glass vials) infused iv on day 1 at 300 mg during the first cycle, followed by infusions of 1000 mg on day 1 of each subsequent cycle
• Bendamustine (powder dissolved in sterile water) infused iv over 30-60 minutes at the dose of 120 mg/m2 (days 2,3 every 21 days) or 120 mg/m2(days 2,3 every 28) or 90 mg/m2 (days 2,3 every 28 days) depending on toxicity
• Dexamethasone administered i.v. at 40 mg (days 1,2,3,4)

Intervention Type: DRUG

Other Intervention Names

Ofatumumab (HuMax-CD20; ARZERRA); Bendamustine (Treanda; Ribomustin)

Eligibility Criteria

Inclusion Criteria

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 D1 overexpression).

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.

Exclusion Criteria

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 abnormalities

5. History of significant cerebrovascular disease or event with significant symptoms or sequelae

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., asthma)

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 be included.

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 result.

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.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: collaborator

Southern Europe New Drug Organization

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alessandro M. Gianni, MD

Role: STUDY_CHAIR

Istituto Nazionale Tumori Milano

Locations

Fondazione IRCCS Istituto Nazionale Tumori

Milan, , Italy

Site Status: RECRUITING

Ospedali Bianchi - Melacrino - Morelli

Reggio Calabria, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Michele Magni, MD

Role: CONTACT

michele.magni@istitutotumori.mi.it

Facility Contacts

Magni Michele, MD

Role: primary

michele.magni@istitutotumori.mi.it

Caterina Stelitano, MD

Role: primary

Other Identifiers

INT5909

Identifier Type: -

Identifier Source: org_study_id