Chronic Lymphocytic LeukemiaPhase 2NCT01310101
Ofatumumab Added to Dexamethasone in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia
A Phase 2 study testing ofatumumab plus dexamethasone in people with Chronic Lymphocytic Leukemia, run by Brno University Hospital at 4 sites in Czechia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- ofatumumab plus dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 4 sitesCzechia
- Study dates
- Apr 2011to Feb 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
Trial locations and contacts
4 sites in 1 country.
Czechia4 sites
University Hospital Brno, Department of Internal Medicine - Hematology and Oncology
Brno, 62500
University Hospital Hradec Králové, Department of clinical hematology
Hradec Králové, 50005
University Hospital Královské Vinohrady, Department of clinical hematology
Prague, 10034
Charles University in Prague and General University Hospital in Prague, 1st Department of medicine - Department of hematology
Prague, 12808
About this study
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.
Read the 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
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- ofatumumab plus dexamethasone
- Keywords
- Chronic Lymphocytic Leukemia, Refractory, Relapse, Ofatumumab, Dexamethasone
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
| Study group | Role | What they receive |
|---|---|---|
| Ofatumumab plus dexamethasone | Experimental | Not described Receives: Drug: ofatumumab plus dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to Week 24
Secondary outcomes (2)
Safety profile of the combination of ofatumumab and dexamethasone
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.
Measured: Up to Week 24
Time dependent parameters: progression-free survival (PFS); overall survival (OS).
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).
Measured: Year 3 after treatment completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2011 (estimated)
- Study startApr 2011
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brno University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Hradec Kralove, Faculty Hospital Kralovske Vinohrady, General Teaching Hospital, Prague
- Responsible party
- Principal investigator, Assoc. Prof. Michael Doubek, M.D., Ph.D, Brno University Hospital
- Investigators
- Jiří Mayer, Prof., M.D., Study director, University Hospital Brno, Department of Internal Medicine - Hematology and OncologyMichael Doubek, A.Prof.,M.D., Principal investigator, University Hospital Brno, Department of Internal Medicine - Hematology and OncologyLukáš Smolej, M.D., Ph.D., Principal investigator, University Hospital Hradec Králové, Department of clinical hematologyTomáš Kozák, Doc.,M.D., Principal investigator, University Hospital Královské Vinohrady, Department of clinical hematologyPetra Obrtlíková, M.D., Ph.D., Principal investigator, Charles University in Prague and General University Hospital in Prague, 1st Department of medicine - Department of hematology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01310101
- Sponsor's protocol ID
- O-DEX-1, OFA 113815
- Status last verified
- Feb 2015
- First submitted
- 7 Mar 2011
- Last updated
- 3 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25645263
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ofatumumab Added to Dexamethasone in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT01310101
- Acronym / sponsor ID
- O-DEX-1, OFA 113815
- Conditions
- Chronic Lymphocytic Leukemia
- Keywords
- Chronic Lymphocytic Leukemia, Refractory, Relapse, Ofatumumab, Dexamethasone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Brno University HospitalUniversity, hospital or other
- Collaborators
- University Hospital Hradec Kralove, Faculty Hospital Kralovske Vinohrady, General Teaching Hospital, Prague
- Study start
- Apr 2011
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 8 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ofatumumab plus dexamethasone | Experimental | Drug: ofatumumab plus dexamethasone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ofatumumab plus dexamethasoneDose 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 | Drug | Ofatumumab plus dexamethasone |
Primary outcome
Overall response rate (complete remission - CR, CRi; partial remission - PR)
Time frame: Up to Week 24
The response (CR, CRi, PR rates) will be assessed at the end of therapy of every patient according to international guideline.
2 secondary outcomes
Safety profile of the combination of ofatumumab and dexamethasone
Time frame: Up to Week 24
Time dependent parameters: progression-free survival (PFS); overall survival (OS).
Time frame: Year 3 after treatment completion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2015.
- Derived from this study: PubMed 25645263Doubek 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.
Related trials for Chronic Lymphocytic Leukemia
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jiří Mayer, Prof., M.D. study director
University Hospital Brno, Department of Internal Medicine - Hematology and Oncology
Michael Doubek, A.Prof.,M.D. principal investigator
University Hospital Brno, Department of Internal Medicine - Hematology and Oncology
Lukáš Smolej, M.D., Ph.D. principal investigator
University Hospital Hradec Králové, Department of clinical hematology
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ofatumumab plus dexamethasone in people with Chronic Lymphocytic Leukemia, run by Brno University Hospital at 4 sites in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (complete remission - CR, CRi; partial remission - PR) (time frame: Up to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01310101, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2015.