Clinical study using the drug GSK525762 in subjects with hematologic malignancies
- Conditions
- Patients with relapsed and/or refractory haematological malignancies (lymphoma, leukemia, or multiple myeloma)MedDRA version: 18.0Level: LLTClassification code 10066481Term: Hematological malignancySystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-000445-39-GB
- Lead Sponsor
- GlaxoSmithKline Research and Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 180
1. Written informed consent provided.
2. Males and females 18 years old or older.
3. In Part 1, subjects must have relapsed and/or refractory hematologic malignancies (leukemias, myeloproliferative neoplasms, lymphomas, and myelomas) for which no standard therapies are available or anticipated to result in remission.
In Part 2, subjects must have Acute Myeloid Leukemia (AML), Multiple Myeloma (MM), or non-Hodgkin’s Lymphoma (NHL).
Subjects with AML (Part 1 and Part 2), are eligible if they:
- have relapsed and/or refractory disease, OR
- are =65 years of age and not candidates for or have refused standard chemotherapy.
In Part 2, the NHL cohort will separately enrol subjects with double- and triple hit lymphoma, so that a minimum of 10 subjects with this subset of disease will be enrolled. To be eligible for this sub-cohort, tumor sample from the subject must demonstrate rearrangement and/or overexpression of MYC and either BCL2 and/or BCL6 genes. Evaluation of double- or triple-hit status may be performed via appropriate local testing, and the determination of double- or triple-hit diagnosis will be at the discretion of the investigator and GSK Medical Monitor.
4. Subjects with a prior history of stem cell transplant are allowed if
- At least months has elapsed from the time of transplant, and
- the subject has recovered from transplant-associated toxicities prior to the first dose of GSK525762, and
- For subjects with a prior history of allogeneic transplant,
- the subject has been off systemic immunosuppressive medications (including but not limited to: cyclosporine, tacrolimus, mycophenolate mofetil, or corticosteroids) for at least 1 month prior to the first dose of GSK525762. Topical steroids are permitted
- there are no signs or symptoms of graft versus host disease, other than Grade 1 skin involvement
5. Eastern Cooperative Oncology Group (ECOG) performance status of =1.
6. Subject must be stable enough to be expected to complete dosing through the DLT observation period as assessed by the investigator.
7. Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
8. A female subject is eligible to participate if she is of:
-Non-childbearing potential defined as pre-menopausal females with a
documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases, a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/mL and estradiol < 40 pg/mL (< 140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods defined in protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least two to four weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
-Child-bearing potential and agrees to use one of the contraception methods (described in section 9.1), for an appropriate period of time (as
1. Haematological malignancy associated with human immunodeficiency virus (HIV) infection or solid organ transplant or history of known Hepatitis B Antigen or positive Hepatitis C antibody (confirmed by Recombinant ImmunoBlot Assay [RIBA], if available or alternately confirmed by Hepatitis C Virus [HCV] RNA).
2. History or concurrent malignancy of solid tumours, except for below.
Exception: Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitively treated may be enrolled even if less than 5 years have elapsed since treatment. Consult the GSK Medical Monitor if unsure whether second malignancies meet requirements specified above.
3. Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery, and/or tumour embolization).
Note: the following are allowed:
Hydroxyurea for proliferative disease
Corticosteroids
Use of hematopoetic growthfactors is permitted at the discretion of the investigator according to published guidelines (e.g., National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), American Society of Hematology (ASH), etc.).
Note: the following are NOT allowed:
Investigational anti-cancer drug within 2 weeks (or 5 half-lives of the drug, whichever is longer) prior to the first dose of GSK525762
Major surgery, radiotherapy, or immunotherapy within 4 weeks of GSK525762.
Chemotherapy regimens with delayed toxicity within the last 4 weeks.
Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks.
Nitrosourea or mitomycin C within the last 6 weeks
4. Evidence of severe of uncontrolled infection.
5. Use of anticoagulants (e.g., warfarin, heparin) at therapeutic levels within 7 days prior to the first dose of GSK525762. Low dose (prophylactic) low molecular weight heparin (LMWH) is permitted. In addition, INR must be monitored in accordance with local institutional practices, as appropriate.
6. Current use of a prohibited medication or requires any of these medications during treatment with the investigational drugs. This includes excluding current medications known or suspected to be associated QT prolongation (see Section 8.3). In addition, any subject who is expected to require a QT prolonging medication while on trial should not be enrolled.
7. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding episodes). Any serious and/or unstable pre-existing medical (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator.
8. Symptomatic or untreated CNS disease.
- Subjects with a history of CNS disease (leukemia, lymphoma or myeloma) are permitted to enrol if they have previously received appropriate therapy and CNS remission has been documented.
- Subject with primary CNS lymphoma (defined as isolated CNS lymphoma without systemic involvement) are excluded from study.
9. Cardiac abnormalities as evidenced by any of the following:
-History or current clinically sig
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method