E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008976 |
E.1.2 | Term | Chronic lymphocytic leukemia |
E.1.2 | System Organ Class | 100000004864 |
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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 examine the efficacy of IPI-145 monotherapy in subjects with CLL or SLL who experienced disease progression after treatment with ofatumumab in Study IPI-145-07
• To examine the efficacy of ofatumumab monotherapy in subjects with CLL or SLL who experienced disease progression after treatment with IPI-145 in Study IPI-145-07 |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety of IPI-145 in subjects with CLL or SLL who experienced disease progression after treatment with ofatumumab in Study IPI-145-07
• To evaluate the safety of ofatumumab in subjects with CLL or SLL who experienced disease progression after treatment with IPI-145 in Study IPI-145-07 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Received either IPI-145 or ofatumumab while participating in Study IPI-145-07 and experienced radiologically-confirmed disease progression
2. Diagnosis of active CLL or SLL that meets at least one of the IWCLL 2008 criteria for requiring treatment (Binet Stage ≥ B and/or Rai Stage ≥ I)
3. Measurable nodal disease by CT
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (corresponds to Karnofsky Performance Status [KPS] ≥60%)
5. For women of childbearing potential (WCBP): negative serum β-human chorionic gonadotropin (βhCG) pregnancy test within 1 week before first dose (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 24 consecutive months [women ≤55 years] or 12 consecutive months [women >55 years])
6. Willingness of male and female subjects who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control from the first dose of study drug to 30 days after the last dose of IPI-145 and for 12 months after last dose of ofatumumab. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception
7. Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
8. Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any study specific screening procedures are performed |
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E.4 | Principal exclusion criteria |
1. Discontinued study participation in Infinity-sponsored IPI-145-07
2. >3 months from confirmed PD on Study IPI-145-07
3. Richter’s transformation or prolymphocytic leukemia.
4. Autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP) that is uncontrolled or requires >20 mg QD of prednisone (or equivalent) to maintain hemoglobin >8.0 g/dL or platelets >10,000 μL without transfusion support.
5. Known central nervous system (CNS) lymphoma or leukemia; subjects with symptoms of CNS disease must have a negative CT scan or negative diagnostic lumbar puncture prior to first dose
6. Use of any anticancer medication post documented PD on Study IPI-145-07 and prior to enrollment
− Corticosteroids to manage CLL/SLL-related symptoms are allowed
7. Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study treatment (defined as requiring IV antimicrobial, antifungal or antiviral agents)
− Subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met and there is no evidence of active infection at Screening and/or Cycle 1 Day 1 predose
8. Human immunodeficiency virus (HIV) infection
9. Prior, current or chronic hepatitis B or hepatitis C infection
10. Pregnant or breastfeeding women |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Response Rate (ORR), with overall response defined as the best response of complete response/remission (CR), CR with incomplete marrow recovery (CRi), partial response/remission (PR), or PR with lymphocytosis (PRwL), according to the IWCLL or revised IWG Response Criteria, with modification for treatment-related lymphocytosis |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening, cycles 4, 8, 12, 18, and 24, and early treatment termination |
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E.5.2 | Secondary end point(s) |
• Treatment-emergent adverse events (TEAEs) and changes in laboratory values
• Duration of Response (DOR), defined as the time from the first documentation of response to first documentation of PD or death due to any cause
• Progression-free survival (PFS), defined as the time from first dose of study treatment to first documentation of progressive disease (PD) or death from any cause |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Screening, cycles 4, 8, 12, 18, and 24, and early treatment termination |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 | No |
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 |
Australia |
Austria |
Belgium |
France |
Germany |
Hungary |
Italy |
New Zealand |
Spain |
United Kingdom |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |