E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic lymphocytic leukaemia |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the improvement in progression free survival (PFS), defined as the time from randomization to the date of disease progression or death due to any cause, in subjects with bulky fludarabine-refractory CLL receiving ofatumumab compared to physicians’ choice. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate overall response rate (ORR) - defined as the percentage of subjects achieving either a confirmed complete response (CR) or a partial response (PR).
• To evaluate overall survival (OS), defined as the time from randomization to death.
• To evaluate the safety and tolerability in subjects with CLL receiving ofatumumab compared to physicians choice during the treatment period
• To evaluate the health-related quality of life in subjects with CLL receiving ofatumumab compared to physicians’ choice, as assessed by changes in patient reported outcome (PRO) measures relative to baseline
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the study treatment(s) that may impact subject eligibility is provided in the IB and summary of product characteristics (SmPC) for Arzerra, and the prescribing information of marketed products used as physicians’ choice.
Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Adults with documented diagnosis of CLL based on the modified IWCLL updated NCI-WG guidelines [Hallek, 2008].
2. Have bulky lymphadenopathy, defined as at least 1 lymph node >5cm
3. The subject must be refractory [Hallek, 2008] to fludarabine treatment, defined as:
a. No response to at least 2 cycles of a fludarabine-containing regimen, or
b. A partial response or better after at least 2 cycles of a fludarabine-containing regimen for a duration of less than 6 months
4. Active disease requiring CLL therapy [Hallek, 2008]
5. Age atleast 18 years of age
6. Had at least 2 prior therapies for CLL
7. ECOG Performance Status of 0-2
8. Signed written informed consent prior to performing any study-specific procedures
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Prior allogeneic stem cell transplantation at any time, or prior autologous stem cell transplantation within 6 months of planned randomization.
2. Treatment with any known unapproved drug substance or experimental therapy within 4 weeks prior to planned dosing, or currently participating in any other interventional clinical study. Note: Participation in any other interventional clinical study after disease progression during post PD follow-up is permitted.
3. Known transformation of CLL (e.g. Richter’s transformation), prolymphocytic leukaemia (PLL), or CNS involvement of CLL.
4. Active Autoimmune Haemolytic Anaemia (AIHA) requiring treatment except if associated with progressive disease requiring anti-CLL treatment.
5. Chronic or current active 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 B or C (positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded*).
* If HBV DNA is negative, subject may be included but must undergo HBV DNA monitoring. Prophylactic antiviral therapy may be initiated at the discretion of the investigator.
6. Known HIV positive.
7. Significant concurrent, uncontrolled medical condition that in the opinion of the investigator contraindicates participation in this study.
8. Other past or current malignancy (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless the tumor was successfully treated with curative intent at least 2 years prior to trial entry or if in the opinion of the investigator it is thought not to affect the subject’s safety, the conduct of the study or the interpretation of the data.
9. Non-protocol corticosteroid usage except a maintenance dose corresponding < or = 10 mg of prednisone at the time of planned dosing.
10. Screening laboratory values:
• Creatinine > 2.0 times upper normal limit (unless normal creatinine clearance) or,
• Total bilirubin > 2.0 times upper normal limit (unless due to liver involvement of CLL or due to Gilbert’s syndrome) or,
• Alanine transaminase (ALT) > 2.5 times upper normal limit (unless due to liver involvement of CLL)
11. Known or suspected hypersensitivity to ofatumumab that in the opinion of the investigator is a contraindication to their participation in the present study
12. Lactating women, women with a positive pregnancy test at Visit 1 or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through one year following last ofatumumab dose. Adequate contraception is defined as abstinence, oral hormonal birth control, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device, and male partner sterilization if male partner is sole partner for that subject. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Improvement in progression-free survival (PFS), which is defined as the time from randomisation to the date of disease progression or death due to any cause. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.6.13.1 | Other scope of the trial description |
Patient Reported Outcomes |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 57 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of trial is last patient last visit |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |