- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01809847
Ofatumumab Induction and Maintenance in Elderly Patients With Poor Risk CLL in the Context of Allogeneic Transplantation
Ofatumumab Induction and Maintenance in Elderly Patients With Poor Risk CLL in the Context of Allogeneic Transplantation(CLL-X4 Trial)
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Baden-Württemberg
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Heidelberg, Baden-Württemberg, Germany, 69120
- UniversitatsKlinikum Heidelberg
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Ulm, Baden-Württemberg, Germany, 89081
- Universitatsklinikum Ulm
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Bayern
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München, Bayern, Germany, 80804
- Städtisches Klinikum München Schwabing
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Brandenburg
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Frankfurt (Oder), Brandenburg, Germany, 15236
- Klinikum Frankfurt (Oder) GmbH
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Hessen
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Wiesbaden, Hessen, Germany, 65191
- Deutsche Klinik für Diagnostik
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Niedersachsen
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Göttingen, Niedersachsen, Germany, 37075
- Universitatsmedizin Gottingen
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Nordrhein-Westfalen
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Düsseldorf, Nordrhein-Westfalen, Germany, 40225
- Universitätsklinikum Düsseldorf
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Köln, Nordrhein-Westfalen, Germany, 50937
- Klinikum der Universität zu Köln
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Rheinland-Pfalz
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Mainz, Rheinland-Pfalz, Germany, 55131
- Klinikum der Johannes Gutenberg Universität
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Sachsen
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Chemnitz, Sachsen, Germany, 09113
- Klinikum Chemnitz GmbH
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Dresden, Sachsen, Germany, 01307
- Universitätsklinikum Dresden
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of CLL according to WHO criteria (Hallek 2008) confirmed by flow cytometry of peripheral blood or bone marrow
- Age > 55 years
Poor-risk disease according to the EBMT CLL Transplant Consensus
- Non-response or early relapse (within 12 months) after purine analogue-containing therapy
- Relapse (within 24 months) after purine analogue combination therapy or treatment of similar efficacy (ie, autologous stem cell transplantation)
- p53 deletion/mutation (del 17p-) requiring treatment
- Measurable disease in the peripheral blood defined by a minimum clonal lymphocyte count of 0.5 GPT/L at the time of study inclusion
- Medically fit patients eligible for allogeneic HCT
- Informed consent for related and unrelated donor search and the goal to perform allogeneic HCT
- Sexually mature males must agree to use adequate and medically accepted method of contraception throughout the study if their sexual partners are woman of child bearing potential (WOCBP) WOCBP must be using an adequate and medically accepted method of contraception to avoid pregnancy throughout the study and for at least 3 months after the study.
- WOCBP includes any female that has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >12 consecutive months); or woman on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level >35mlU/mL.
- WOCBP must have a negative serum or urine pregnancy test prior to the start of the study.
Exclusion Criteria:
- Richter's transformation in current relapse or active disease
- Prior allogeneic HCT
- 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 participation in any other interventional clinical study
- Non-response to monotherapy with ofatumumab prior to study inclusion
- Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (left ventricular ejection fraction < 50%)
- Abnormal renal function defined by an estimated GFR < 50 ml/min
- Abnormal lung function tests defined by a DLCO <50%, FEV1%VC <70% despite appropriate treatment
- Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg or HBcAb
- Positive serology for hepatitis C (HC) defined as a positive test for anti-HCV, confirmed by PCR
Screening laboratory values:
- total bilirubin >1.5 times upper normal limit (unless due to AIHA or a known history of Gilbert's disease)
- ALT or AST >2.5 times upper normal limit
- Gamma glutamyl transpeptidase (GGT) >2.5 times upper normal limit (unless due to disease involvement of the liver)
- Other past or current hematologic or solid organ malignancy. Subjects who have been free of malignancy for at least 3 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.
- Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.
- Pregnant or lactating woman
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Ofatumumab
First dose of 300 mg Ofatumumab followed by seven weekly infusions of 2000 mg.
Dexamethasone will be given orally at doses of 40 mg on days 1-4 in weeks 1, 3, 5, and 7. Maintenance therapy consists of 6 monthly infusions of 1000 mg ofatumumab.
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Study treatment comprises eight weeks of induction therapy with ofatumumab in combination with high-dose dexamethasone. The first dose of ofatumumab is 300 mg followed by seven infusions of 2000 mg ofatumumab. Dexamethasone will be given orally at doses of 40 mg on days 1-4 in weeks 1, 3, 5, and 7. Patients who achieved a CR, PR shall proceed to maintenance therapy. Maintenance therapy consists of 6 monthly infusions of 1000 mg ofatumumab. An HLA-matched sibling donor or HLA-matched unrelated donor can be identified for approximately 70% of patients. Donor search will be completed within six weeks for 95% of the patients. Patients with a donor will proceed to allogeneic HCT as soon as possible prior to, or during maintenance therapy.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response rate after induction therapy
Time Frame: week 9
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efficacy analysis of anti-CD20 blockade with ofatumumab
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week 9
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rate of MRD-negative patients
Time Frame: baseline, week 9, month 14
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rate of MRD-negative patients who did not experience relapse, progression or death within the first 14 months after study enrollment
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baseline, week 9, month 14
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of allogeneic HCT
Time Frame: month 9
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Rate of patients who reach allogeneic HCT if HLA-matched donor is available
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month 9
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adverse drug reactions grade III/IV
Time Frame: week 1 till week 9; month 4 till month 9; month 12; month 14; until 30 days after last administration of the study medication
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week 1 till week 9; month 4 till month 9; month 12; month 14; until 30 days after last administration of the study medication
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Overall, event-, and progression free survival
Time Frame: week 1 till week 9; month 4 till month 9; month 12; month 14; up to 5 years follow-up
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week 1 till week 9; month 4 till month 9; month 12; month 14; up to 5 years follow-up
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relapse incidence
Time Frame: month 4 till month 9; month 12; month 14; up to 5 years follow-up
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month 4 till month 9; month 12; month 14; up to 5 years follow-up
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non-relapse mortality
Time Frame: week 1 till week 9; month 4 till month 9; month 12; month 14; up to 5 years follow-up
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week 1 till week 9; month 4 till month 9; month 12; month 14; up to 5 years follow-up
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Incidences of acute and chronic GVHD
Time Frame: during maintenance therapy; month 12, month 14; up to 5 years follow-up
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provided that allogeneic HCT was conducted
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during maintenance therapy; month 12, month 14; up to 5 years follow-up
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Johannes Schetelig, PD Dr. med., Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I, 01307 Dresden
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- TUD-CLL-X4-054
- 2012-001947-31 (EUDRACT_NUMBER)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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