Study to assess the safety and efficacy of the study drug IPI-145 in Leukaemia patients compared with Ofatumumab
- Conditions
- Chronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaMedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-002405-61-AT
- Lead Sponsor
- Verastem, INC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 307
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
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 207
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
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 bypa
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<br>from randomization to first documentation of progressive disease (PD)<br>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<br>study treatment
- Secondary Outcome Measures
Name Time Method