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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2011 by Southern Europe New Drug Organization.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Information provided by (Responsible Party):
Southern Europe New Drug Organization
ClinicalTrials.gov Identifier:
NCT01221103
First received: October 13, 2010
Last updated: September 12, 2011
Last verified: September 2011
  Purpose

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 The choice of the doses for the combination is based on the investigators unpublished clinical experience, as well as inferred from extensive experimental data on the use of other monoclonal antibodies in combination chemotherapy in lymphoma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.


Condition Intervention Phase
Lymphoma, Mantle-Cell
Drug: Combination of dexamethasone, ofatumumab and bendamustine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Dexamethasone, Ofatumumab and Bendamustine [Treanda] (DOT) as First-line Treatment of Mantle-cell Lymphoma (MCL) in the Elderly

Resource links provided by NLM:


Further study details as provided by Southern Europe New Drug Organization:

Primary Outcome Measures:
  • Adverse events (Phase I) [ Time Frame: 60 days after last dose of investigational drug ] [ Designated as safety issue: Yes ]
    Incidence, severity, and attribution of treatment-emergent AEs

  • Complete Response rate (Phase II) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Response determined according to the revised response criteria for malignant lymphoma (Cheson, JCO 2008)


Secondary Outcome Measures:
  • Duration of response (Phase II) [ Time Frame: At the screening, cycle 4 (12 weeks) , cycle 6 (18 weeks), 1 year Follow-up ] [ Designated as safety issue: No ]
    Duration estimated from the first confirmed tumor regression to the disease progression.

  • Serial peripheral blood CD34+ cell counts [ Time Frame: Cycles 1 (3 weeks), 4 (12 weeks) and 6 (18 weeks) ] [ Designated as safety issue: No ]
  • Molecular analysis of CD34+ cells [ Time Frame: cycle 4 (12 weeks) or cycle 6 (18 weeks for inadequate harvests after cycle 4) ] [ Designated as safety issue: No ]
  • Serial molecular analysis of peripheral blood cells [ Time Frame: Cycles 1 (3 weeks), 4 (12 weeks) and 6 (18 weeks) ] [ Designated as safety issue: No ]
    Serial molecular analysis by PCR

  • Ability to harvest ≥ 7 x106 CD34+ cells/kg [ Time Frame: Cycle 4 (12 weeks) or cycle 6 (18 weeks for inadequate harvests after cycle 4) ] [ Designated as safety issue: No ]
  • Presence of tumor cells in the peripheral blood [ Time Frame: Cycle 1 (3 weeks), 4 (12 weeks) and 6 (18 weeks) ] [ Designated as safety issue: No ]
    Monitored by morphology, immunophenotype and PCR


Estimated Enrollment: 50
Study Start Date: April 2010
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DOT
Combination of dexamethasone, ofatumumab and bendamustine
Drug: 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)
Other Names:
  • Ofatumumab (HuMax-CD20; ARZERRA)
  • Bendamustine (Treanda; Ribomustin)

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01221103

Contacts
Contact: Michele Magni, MD michele.magni@istitutotumori.mi.it

Locations
Italy
Fondazione IRCCS Istituto Nazionale Tumori Recruiting
Milano, Italy, 20133
Contact: Magni Michele, MD       michele.magni@istitutotumori.mi.it   
Principal Investigator: Alessandro M. Gianni, MD         
Ospedali Bianchi - Melacrino - Morelli Recruiting
Reggio Di Calabria, Italy, 89100
Contact: Caterina Stelitano, MD         
Principal Investigator: Caterina Stelitano, MD         
Sponsors and Collaborators
Southern Europe New Drug Organization
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Investigators
Study Chair: Alessandro M. Gianni, MD Istituto Nazionale Tumori Milano
  More Information

No publications provided

Responsible Party: Southern Europe New Drug Organization
ClinicalTrials.gov Identifier: NCT01221103     History of Changes
Other Study ID Numbers: INT5909
Study First Received: October 13, 2010
Last Updated: September 12, 2011
Health Authority: Italy: Competent Authority

Keywords provided by Southern Europe New Drug Organization:
Dexamethasone
Ofatumumab
Bendamustine
Lymphoma, Mantle-Cell
Non-Hodgkin lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bendamustine
Nitrogen Mustard Compounds
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors

ClinicalTrials.gov processed this record on August 18, 2014