NCT01310101

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
33

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Apr 2011

Typical duration for phase_2

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 7, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 8, 2011

Completed
24 days until next milestone

Study Start

First participant enrolled

April 1, 2011

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2015

Completed
Last Updated

February 3, 2015

Status Verified

February 1, 2015

Enrollment Period

3.8 years

First QC Date

March 7, 2011

Last Update Submit

February 1, 2015

Conditions

Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic LeukemiaRefractoryRelapseOfatumumabDexamethasone

Outcome Measures

Primary Outcomes (1)

  • Overall response rate (complete remission - CR, CRi; partial remission - PR)

    The response (CR, CRi, PR rates) will be assessed at the end of therapy of every patient according to international guideline.

    Up to Week 24

Secondary Outcomes (2)

  • Safety profile of the combination of ofatumumab and dexamethasone

    Up to Week 24

  • Time dependent parameters: progression-free survival (PFS); overall survival (OS).

    Year 3 after treatment completion

Study Arms (1)

Ofatumumab plus dexamethasone

EXPERIMENTAL
Drug: ofatumumab plus dexamethasone

Interventions

ofatumumab plus dexamethasoneDRUG

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

Ofatumumab plus dexamethasone

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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)
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

University Hospital Brno, Department of Internal Medicine - Hematology and Oncology

Brno, 62500, Czechia

Location

University Hospital Hradec Králové, Department of clinical hematology

Hradec Králové, 50005, Czechia

Location

University Hospital Královské Vinohrady, Department of clinical hematology

Prague, 10034, Czechia

Location

Charles University in Prague and General University Hospital in Prague, 1st Department of medicine - Department of hematology

Prague, 12808, Czechia

Location

Related Publications (1)

  • Doubek M, Brychtova Y, Panovska A, Sebejova L, Stehlikova O, Chovancova J, Malcikova J, Smardova J, Plevova K, Volfova P, Trbusek M, Mraz M, Bakesova D, Trizuljak J, Hadrabova M, Obrtlikova P, Karban J, Smolej L, Oltova A, Jelinkova E, Pospisilova S, Mayer J. Ofatumumab added to dexamethasone in patients with relapsed or refractory chronic lymphocytic leukemia: Results from a phase II study. Am J Hematol. 2015 May;90(5):417-21. doi: 10.1002/ajh.23964. Epub 2015 Apr 1.

    PMID: 25645263DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-CellRecurrence

Interventions

ofatumumabDexamethasone

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, Fluorinated

Study Officials

  • Jiří Mayer, Prof., M.D.

    University Hospital Brno, Department of Internal Medicine - Hematology and Oncology

    STUDY DIRECTOR

  • 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

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
M.D., Ph.D.

Study Record Dates

First Submitted

March 7, 2011

First Posted

March 8, 2011

Study Start

April 1, 2011

Primary Completion

February 1, 2015

Study Completion

February 1, 2015

Last Updated

February 3, 2015

Record last verified: 2015-02

Locations

CZ(4)