Ofatumumab Added to Dexamethasone in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2011 by Brno University Hospital
Sponsor:
Collaborators:
University Hospital Hradec Kralove
Faculty Hospital Kralovske Vinohrady
General Teaching Hospital, Prague
Information provided by (Responsible Party):
Assoc. Prof. Michael Doubek, M.D., Ph.D, Brno University Hospital
ClinicalTrials.gov Identifier:
NCT01310101
First received: March 7, 2011
Last updated: October 16, 2011
Last verified: April 2011
  Purpose

The rationale of the study is to explore the safety and efficacy of ofatumumab in combination with dexamethasone (O-dex regimen) in patients with refractory/relapsed CLL. Moreover, the hypothesis is that this approach will be able to achieve at least the same response rates compared with R-dex regimens (historical controls; manuscript submitted to Leukemia), while maintaining lower toxicity profile.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: ofatumumab plus dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Ofatumumab Added to Dexamethasone in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Brno University Hospital:

Primary Outcome Measures:
  • Overall response rate (complete remission - CR, CRi; partial remission - PR) [ Time Frame: Up to Week 24 ] [ Designated as safety issue: Yes ]
    The response (CR, CRi, PR rates) will be assessed at the end of therapy of every patient according to international guideline.


Secondary Outcome Measures:
  • Safety profile of the combination of ofatumumab and dexamethasone [ Time Frame: Up to Week 24 ] [ Designated as safety issue: Yes ]

    Safety of the treatment will be evaluated by: adverse events, laboratory tests, vital signs, electrocardiogram and performance status.

    The safety analysis population will include all subjects who receive at least one dose/infusion and a baseline safety assessment.


  • Time dependent parameters: progression-free survival (PFS); overall survival (OS). [ Time Frame: Year 3 after treatment completion ] [ Designated as safety issue: No ]
    PFS and OS will be summarized using Kaplan-Meier plots. Median and the corresponding 95% CI (using Greenwood's formula) will be provided as appropriate. In addition these will be compared with the corresponding plots of a previous study R-dex using one sample log-rank test as described in Finkelstein et al. (J Nat Cancer Inst, 2003).


Estimated Enrollment: 30
Study Start Date: April 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ofatumumab plus dexamethasone Drug: ofatumumab plus dexamethasone

Dose and schedule

Cycle 1:

Ofatumumab: 300 mg as an i.v. infusion on day 1 of the cycle; Ofatumumab: 2000 mg as an i.v. infusion on days 8, 15, 22; Dexamethasone: 40 mg/day p.o., days 1-4 and 15-18

Cycles 2 to 6 (cycles every 28 days):

Ofatumumab: 1000 mg i.v. infusion on day 1, 8, 15 and 22 of the cycle; Dexamethasone: 40 mg/day p.o., days 1-4 and 15-18


Detailed Description:

This is an open-label, multi-center, non-randomized, phase II study to evaluate the safety and efficacy of ofatumumab added to dexamethasone in subjects with relapsed or refractory chronic lymphocytic leukemia.

The treatment will be given for a minimum of 3 cycles, until the best response, or up to a maximum of 6 cycles. After completion of the treatment phase in all patients, survival and disease status assessments will be performed in 1 month post treatment, and then every 2 months for 3 years. The patient will be followed-up in the study for 3 years if there is no progression.

Dose and schedule Cycle 1: Ofatumumab: 300 mg as an i.v. infusion on day 1 of the cycle Ofatumumab: 2000 mg as an i.v. infusion on days 8, 15, 22; Dexamethasone: 40 mg/day p.o., days 1-4 and 15-18; Cycles 2 to 6 (cycles every 28 days): Ofatumumab: 1000 mg i.v. infusion on day 1, 8, 15 and 22 of the cycle; Dexamethasone: 40 mg/day p.o., days 1-4 and 15-18.

Response will be assessed according to the IWCLL guidelines. The investigator assessment of response and progression will be considered primary for all endpoints described in the study.

Safety of the treatment will be evaluated by: adverse events, laboratory tests, vital signs, electrocardiogram and performance status.

Study Endpoints

Primary Endpoint:

Overall response rate (CR, CRi, PR rates)

Secondary Endpoints:

Toxicity, tolerability, adverse events (these events will be assessed by investigator and by the independent reviewers at the key time-points) Overall survival Progression-free survival Time to response and duration of response Time to progression and time to next therapy

Other/Exploratory Endpoints:

Exploratory molecular genetic, immunophenotypic, cytogenetic and pharmacologic markers

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female previously treated patients with B-cell CLL requiring therapy according to the revised NCI criteria (including CLL patients with immune-mediated hemolysis or thrombocytopenia).
  • Flow cytometry confirmation of CLL immunophenotype with CD5, CD19, CD20, CD23, CD79b, and surface Ig at screening.
  • Disease recurrence (or refractory disease) after at least one fludarabine-containing regimen, or after at least two previous chemotherapy regimens without fludarabine; and/or poor marrow reserve not allowing chemotherapy administration (Absolute Neutrophil Count < 1.0 x 109/L and/or Absolute Platelet Count < 50 x 109/L).
  • Age ≥ 18 years old.
  • Signed written informed consent.
  • Life expectancy > 3 months.
  • ECOG performance status ≤ 2.
  • CT scan performed.

Exclusion Criteria:

  • 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).
  • Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study.
  • 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.
  • Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to start of therapy.
  • 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.
  • History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae.
  • Known HIV positive.
  • Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.
  • Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.
  • Positive serology for Hepatitis B (HBV) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded. See section 10.3.2.1 Hepatitis B screening.
  • Positive serology for hepatitis C (HCV) defined as a positive test for anti-HCVAb, in which case reflexively perform a HCV RIBA immunoblot assay on the same sample to confirm the result
  • Screening laboratory values:

    • creatinine > 2.0 times upper normal limit
    • total bilirubin >1.5 times upper normal limit (unless due to CLL involvement of liver or a known history of Gilbert's disease)
    • ALT > 2.5 times upper normal limit (unless due to disease involvement of liver)
    • alkaline phosphatase > 2.5 times upper normal limit (unless due to disease involvement of the liver or bone marrow)
  • Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening.
  • Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy.
  • Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.
  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: NCT01310101

Contacts
Contact: Michael Doubek, MD, PhD +420 532 233 562 mdoubek@fnbrno.cz

Locations
Czech Republic
University Hospital Brno, Department of Internal Medicine - Hematology and Oncology Recruiting
Brno, Czech Republic, 62500
Principal Investigator: Michael Doubek, A.Prof.,M.D.         
University Hospital Hradec Králové, Department of clinical hematology Recruiting
Hradec Králové, Czech Republic, 50005
Principal Investigator: Lukáš Smolej, MD, PhD         
University Hospital Královské Vinohrady, Department of clinical hematology Not yet recruiting
Prague, Czech Republic, 10034
Principal Investigator: Tomáš Kozák, MD, PhD         
Charles University in Prague and General University Hospital in Prague, 1st Department of medicine - Department of hematology Recruiting
Prague, Czech Republic, 12808
Principal Investigator: Petra Obrtlíková, MD, PhD         
Sponsors and Collaborators
Brno University Hospital
University Hospital Hradec Kralove
Faculty Hospital Kralovske Vinohrady
General Teaching Hospital, Prague
Investigators
Study Director: Jiří Mayer, Prof., M.D. University Hospital Brno, Department of Internal Medicine - Hematology and Oncology
Principal Investigator: Michael Doubek, A.Prof.,M.D. University Hospital Brno, Department of Internal Medicine - Hematology and Oncology
Principal Investigator: Lukáš Smolej, M.D., Ph.D. University Hospital Hradec Králové, Department of clinical hematology
Principal Investigator: Tomáš Kozák, Doc.,M.D. University Hospital Královské Vinohrady, Department of clinical hematology
Principal Investigator: Petra Obrtlíková, M.D., Ph.D. Charles University in Prague and General University Hospital in Prague, 1st Department of medicine - Department of hematology
  More Information

No publications provided

Responsible Party: Assoc. Prof. Michael Doubek, M.D., Ph.D, M.D., Ph.D., Brno University Hospital
ClinicalTrials.gov Identifier: NCT01310101     History of Changes
Other Study ID Numbers: O-DEX-1, OFA 113815
Study First Received: March 7, 2011
Last Updated: October 16, 2011
Health Authority: Czech Republic: State Institute for Drug Control

Keywords provided by Brno University Hospital:
Chronic Lymphocytic Leukemia
Refractory
Relapse
Ofatumumab
Dexamethasone

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
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
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014