Study to assess the safety and efficacy of the study drug IPI-145/Duvelisib in Leukaemia patients compared with Ofatumumab

Phase 1

Conditions: Chronic Lymphocytic LeukemiaSmall Lymphocytic Lymphoma
Therapeutic area: Diseases [C] - Cancer [C04]
MedDRA version: 20.1Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 100000004864

Registration Number: EUCTR2013-002405-61-HU

Lead Sponsor: Verastem, Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 319

Inclusion Criteria

Subjects are eligible for inclusion in the study if they meet the following 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 National Comprehensive Cancer Network [NCCN] or European Society for Medical Oncology [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 fluorescence in situ hybridization (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 evaluated as part of the screening laboratory evaluation to inform stratification
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 duvelisib at the dose and schedule defined in the protocol
9.Must meet the following laboratory parameters:
a.Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) = 3 x upper limit of normal (ULN)
b.Total bilirubin = 1.5 x ULN
c.Serum creatinine = 2.0 x ULN
d.Hemoglobin = 8.0 g/dL with or without transfusion support
e.Platelet count = 10,000 µL with or without transfusion support
10.For women of childbearing potential (WCBP): negative serum ß-human chorionic gonadotropin (ßhCG) 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])
11.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 duvelisib and for 12 months after last dose of ofatumumab. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception
12.Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
13.Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any study specific screening procedures are performed
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 129

Exclusion Criteria

Subjects are to be excluded from the study if they meet any of the following 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 once daily (QD) of prednisone (or equivalent) to maintain hemoglobin > 8.0 g/dL or platelets > 10,000 µL without transfusion support
3.Refractory to ofatumumab (defined as progression or relapse <12 months of receiving ofatumumab monotherapy or < 24 months of receiving an ofatumumab-containing regimen)
4.Prior allogeneic transplant (prior autologous stem cell transplant >6 months prior to study entry is permitted)
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 randomization
6.Prior exposure to a phosphoinositide-3-kinase (PI3K) inhibitor (eg, GS-1101, duvelisib) or a Bruton’s tyrosine kinase (BTK) inhibitor
7.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
8.Ongoing treatment with chronic immunosuppressants (eg, cyclosporine) or systemic steroids > 20 mg prednisone (or equivalent) QD
9.History of tuberculosis treatment within the preceding two years
10.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 randomization
11.Human immunodeficiency virus (HIV) infection
12.Prior, current, or chronic hepatitis B or hepatitis C infection
13.History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
14.Unable to receive prophylactic treatment for pneumocystis or herpes simplex virus (HSV)
15.Baseline QT interval corrected with Fridericia’s method (QTcF) > 480 ms (average of triplicate readings) Note: This criterion does not apply to subjects with a right or left bundle branch block (BBB)
16.Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition), or any important medical illness or abnormal laboratory finding that would, in the investigator’s judgment, increase the subject’s risk while participating in this study
17.Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix, bladder, or prostate not requiring treatment. Subjects with previous malignancies are eligible provided that they have been disease free for =2 years
18.History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
19.Administration of medications or foods that are strong inhibitors or inducers of CYP3A within 2 weeks of randomization
20.Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
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Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: •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);Secondary Objective: •To determine the safety of IPI-145 in subjects with CLL and SLL<br>•To evaluate the pharmacokinetics (PK) of IPI-145 and, if applicable, its metabolite(s)<br>;Primary end point(s): The primary endpoint is progression-free survival (PFS), defined as time from randomization to first documentation of progressive disease (PD) as determined by independent review or death due to any cause.;Timepoint(s) of evaluation of this end point: Screening, cycles 3, 5, 7, 11, 15 and 19, and early termination from study treatment

Secondary Outcome Measures

Name	Time	Method

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