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 versus ofatumumab monotherapy in subjects with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) |
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E.2.2 | Secondary objectives of the trial |
•To determine the safety of IPI-145 in subjects with CLL and SLL
•To evaluate the pharmacokinetics (PK) of IPI-145 and, if applicable, its metabolite(s)
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There is an optional sub study for Pharmacogenomics. There is not a separate protocol, it is included in the main protocol. |
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E.3 | Principal inclusion criteria |
1. ≥18 years of age
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. Disease that has progressed during or relapsed after at least one previous CLL/SLL therapy
4. Not appropriate for treatment with a purine-based analogue regimen (per NCCN or ESMO guidelines), including relapse ≤36 months from a purine-based chemoimmunotherapy regimen or relapse ≤24 months from a purine-based monotherapy regimen
5. A cytogenetics or FISH analysis of the leukemic cells within 24 months of randomization is required to document the presence or absence of del(17p). Note: if a sample from within 24 months is not available, it should be collected as part of the screening laboratory evaluation
6. Measurable disease with a lymph node or tumor mass ≥1.5 cm in at least one dimension as assessed by computed tomography (CT)
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (corresponds to Karnofsky Performance Status [KPS] ≥60%)
8. Willingness by subject to be randomized to receive either ofatumumab or IPI-145 at the dose and schedule defined in the protocol
9. For women of childbearing potential (WCBP): negative serum β-human chorionic gonadotropin (βhCG) pregnancy test within 1 week before randomization (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])
10. 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
11. Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
12. 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. History of Richter's transformation or prolymphocytic leukemia
2. Autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) that is uncontrolled or requiring >20 mg QD of prednisone (or equivalent) to maintain hemoglobin >8.0 g/dL or platelets >10,000 μL without transfusion support
3. Prior allogeneic transplant (prior autologous stem cell transplant >6 months prior to study entry is permitted)
4. 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 randomization
5. Prior exposure to a PI3K inhibitor (eg, GS-1101, IPI-145) or a BTK inhibitor
6. Use of any of the following medications or procedures within the specified timeframe:
− Use of live or live attenuated vaccines within 30 days prior to randomization
− Chemotherapy, radiation therapy, or ablative therapy within 3 weeks of randomization
− Tyrosine kinase inhibitor within 7 days of randomization
− Other investigational therapy (not included above) within 3 weeks of randomization
7. History of tuberculosis treatment within the preceding two years
8. Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study treatment (defined as requiring intravenous [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 randomization
9. Human immunodeficiency virus (HIV) infection
10. Prior, current or chronic hepatitis B or hepatitis C infection
11. History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
12. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
13. Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
14. Major surgery or invasive intervention within 4 weeks prior to randomization
15. Pregnant or breastfeeding women |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival (PFS), defined as time from randomization to the first documentation of progressive disease (PD) or death due to any cause |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening, cycles 3, 5, 7, 11, 15 and 19, and early termination from study treatment |
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E.5.2 | Secondary end point(s) |
ORR, Lymph node response rate, Hematologic improvement |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Screening, cycles 3, 5, 7, 11, 15 and 19, and early termination from study treatment
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | 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 | No |
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.8.2.4 | 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 | Yes |
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 | 5 |
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 | 5 |
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 |