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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01943851

Additional trial details provided through ANZCTR are available at the end of this record.

Registration number

NCT01943851

Ethics application status

Date submitted

12/09/2013

Date registered

17/09/2013

Titles & IDs

Public title

A Dose Escalation Study to Investigate the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD) and Clinical Activity of GSK525762 in Subjects With Relapsed, Refractory Hematologic Malignancies

Scientific title

A Phase I/II Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK525762 in Subjects With Relapsed, Refractory Hematologic Malignancies

Secondary ID [1]

2013-000445-39

Secondary ID [2]

116183

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Neoplasms

Condition category

Condition code

Cancer

Leukaemia - Acute leukaemia

Cancer

Leukaemia - Chronic leukaemia

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - GSK525762

Experimental: Part 1: GSK525762 QD Cohort - Subject will be administered a 5 milligram (mg) starting dose of GSK525762, oral tablets, QD. Dose escalations will be performed in Part 1 and dose adjustments are allowed to address tolerability and safety issues. Thereafter, subjects will be enrolled in a standard 3+3 design. Separate dose escalation cohorts will be opened for subjects with AML, NHL, and MM for QD dosing. Dose escalation will continue until an MTD is determined or until a dose of 200 mg per day is reached.

Experimental: Part 1: GSK525762 BID Cohort - Subject will be administered a starting dose of GSK525762, oral tablets, 20 mg BID (12 hours apart, total daily dose of 40 mg). Dose escalations will be performed in Part 1 and dose adjustments are allowed to address tolerability and safety issues. Thereafter, subjects will be enrolled in a standard 3+3 design. Separate dose escalation cohorts will be opened for subjects with AML, NHL, and MM, for BID dosing. Dose escalation will continue until an MTD is determined or until a dose of 200 mg per day is reached.

Experimental: Part 2: GSK525762 dose expansion cohort - After the MTD has been determined in Part1, Part 2 dose expansion cohorts will be opened for AML, NHL and MM.

Treatment: Drugs: GSK525762
GSK525762 1 mg, 10 mg and 30 mg will be supplied as white to off-white, amorphous free base and white to slightly colored crystalline besylate tablets, round, biconvex tablets with no markings. GSK525762 will be administered with 240 milliliter (mL) water.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD)

Timepoint [1]

Up to 86.9 weeks

Primary outcome [2]

Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

Timepoint [2]

Up to 3 weeks

Primary outcome [3]

Part 1: Number of Participants With Dose Reductions

Timepoint [3]

Up to 86.9 weeks

Primary outcome [4]

Part 1: Number of Participants With Any Dose Interruptions or Delays

Timepoint [4]

Up to 86.9 weeks

Primary outcome [5]

Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters

Timepoint [5]

Up to 86.9 weeks

Primary outcome [6]

Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters

Timepoint [6]

Up to 86.9 weeks

Primary outcome [7]

Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method

Timepoint [7]

Up to 86.9 weeks

Primary outcome [8]

Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature

Timepoint [8]

Up to 86.9 weeks

Primary outcome [9]

Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

Timepoint [9]

Up to 86.9 weeks

Primary outcome [10]

Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading)

Timepoint [10]

Up to 86.9 weeks

Primary outcome [11]

Part 2: Objective Response Rate (ORR) (MDS Cohort)

Timepoint [11]

Up to 36.4 weeks

Primary outcome [12]

Part 2: Objective Response Rate Lasting at Least 4 Months (ORR4) (CTCL Cohorts)

Timepoint [12]

Up to 36.4 weeks

Secondary outcome [1]

Part 1: Overall Response Rate (ORR)- Investigator Assessment

Timepoint [1]

Up to 86.9 weeks

Secondary outcome [2]

Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration

Timepoint [2]

Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [3]

Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration

Timepoint [3]

Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [4]

Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration

Timepoint [4]

Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [5]

Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration

Timepoint [5]

Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [6]

Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration

Timepoint [6]

Week 2 Day 7: Pre-dose on Days 4, 6 and 7

Secondary outcome [7]

Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration

Timepoint [7]

Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [8]

Part 1: Tmax of GSK525762 Following Repeat Dose Administration

Timepoint [8]

Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [9]

Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration

Timepoint [9]

Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [10]

Part 1: T1/2 of GSK525762 Following Repeat Dose Administration

Timepoint [10]

Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [11]

Part 1: Time Invariance (RS) of GSK525762

Timepoint [11]

Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [12]

Part 1: Accumulation Ratio (RO) of GSK525762

Timepoint [12]

Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [13]

Part 2: Apparent Clearance (CL/F) of GSK525762 After Single Dose Administration

Timepoint [13]

Week 1 Day 1: pre-dose and at 0.5 - 2 hour, 4 - 8 hours post-dose

Secondary outcome [14]

Part 2: Apparent Clearance (CL/F) of GSK525762 After Repeat Dose Administration

Timepoint [14]

Week 3 Day 1: pre-dose and at 0.5 - 2 hour, 4 - 8 hours post-dose

Secondary outcome [15]

Part 2: Apparent Central Volume of Distribution (V1/F) of GSK525762 Following Single Dose Administration

Timepoint [15]

Week 1 Day 1: pre-dose and at 0.5 - 2 hour, 4 - 8 hours post-dose

Secondary outcome [16]

Part 2: Apparent Central Volume of Distribution (V1/F) of GSK525762 Following Repeat Dose Administration

Timepoint [16]

Week 3 Day 1: pre-dose and at 0.5 - 2 hour, 4 - 8 hours post-dose

Secondary outcome [17]

Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration

Timepoint [17]

Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [18]

Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration

Timepoint [18]

Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [19]

Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration

Timepoint [19]

Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [20]

Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration

Timepoint [20]

Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [21]

Part 1: Trough Concentration (Ctau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration

Timepoint [21]

Week 2 Day 7: Pre-dose on Days 4, 6 and 7

Secondary outcome [22]

Part 1: Tmax of GSK3529246 (Active Metabolite) Following Single Dose Administration

Timepoint [22]

Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [23]

Part 1: Tmax of GSK3529246 (Active Metabolite) Following Repeat Dose Administration

Timepoint [23]

Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [24]

Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Single Dose Administration

Timepoint [24]

Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [25]

Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Repeat Dose Administration

Timepoint [25]

Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [26]

Part 1: Time Invariance (RS) of GSK3529246 (Active Metabolite)

Timepoint [26]

Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [27]

Part 1: Accumulation Ratio (RO) of GSK3529246 (Active Metabolite)

Timepoint [27]

Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

Secondary outcome [28]

Part 2: Apparent Clearance (CL/F) of GSK3529246 (Active Metabolite) Following Single Dose Administration

Timepoint [28]

Week 1 Day 1: pre-dose and at 0.5 - 2 hours, 4 - 8 hours post-dose

Secondary outcome [29]

Part 2: Apparent Clearance (CL/F) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration

Timepoint [29]

Week 3 Day 1: pre-dose and at 0.5 - 2 hours, 4 - 8 hours post-dose

Secondary outcome [30]

Part 2: Apparent Central Volume of Distribution (V1/F) of GSK3529246 (Active Metabolite) Following Single Dose Administration

Timepoint [30]

Week 1 Day 1: pre-dose and at 0.5 - 2 hours, 4 - 8 hours post-dose

Secondary outcome [31]

Part 2: Apparent Central Volume of Distribution (V1/F) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration

Timepoint [31]

Week 3 Day 1: pre-dose and at 0.5 - 2 hours, 4 - 8 hours post-dose

Secondary outcome [32]

Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort

Timepoint [32]

Baseline (pre-dose Week1 Day1) and Week 3, Week 7, Week 10, Week 16 and Week 24

Secondary outcome [33]

Part 2: Number of Participants With Non-serious AEs and SAEs and AELDs

Timepoint [33]

Up to 36.4 weeks

Secondary outcome [34]

Part 2: Number of Participants With Dose Reductions

Timepoint [34]

Up to 36.4 weeks

Secondary outcome [35]

Part 2: Number of Participants With Dose Interruptions/Delays

Timepoint [35]

Up to 36.4 weeks

Secondary outcome [36]

Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters

Timepoint [36]

Up to 36.4 weeks

Secondary outcome [37]

Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters

Timepoint [37]

Up to 36.4 weeks

Secondary outcome [38]

Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method

Timepoint [38]

Up to 36.4 weeks

Secondary outcome [39]

Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature

Timepoint [39]

Up to 36.4 weeks

Secondary outcome [40]

Part 2: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: DBP and SBP

Timepoint [40]

Up to 36.4 weeks

Secondary outcome [41]

Part 2: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading)

Timepoint [41]

Up to 36.4 weeks

Secondary outcome [42]

Part 2: Progression Free Survival (PFS)

Timepoint [42]

Up to 36.4 weeks

Secondary outcome [43]

Part 2: Duration of Response (DOR)

Timepoint [43]

Up to 36.4 weeks

Secondary outcome [44]

Part 2: Overall Survival (OS)

Timepoint [44]

Up to 36.4 weeks

Eligibility

Key inclusion criteria

Inclusion criteria

* Written informed consent provided.
* Males and females 18 years old or older.
* In Part 1 and, Part 2, subjects must have AML, MM, or NHL. Subjects with AML, 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. Subjects with multiple myeloma are eligible if they have progressed despite therapy with an alkylating agent, proteasome inhibitor, and immunomodulatory agent, either as individual regimens or in combination. Subjects with NHL are eligible if they have received at least two prior lines of systemic therapy, including at least one line of immunochemotherapy with an anti-CD20 antibody (if their tumor expresses CD20).

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.

* Subjects with a prior history of stem cell transplant (autologous and/or allogeneic) are allowed if

* At least 3 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.
* Eastern Cooperative Oncology Group (ECOG) performance status of <=1.
* Subject must be stable enough to be expected to complete dosing through the DLT observation period as assessed by the investigator.
* 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.
* 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 milli-International units per milliliter and estradiol < 40 picograms per milliliter (< 140 picomole per liter) 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 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until at least 7 months after the last dose of study medication; Negative serum pregnancy test <= 7 days prior to first study drug dose; Female subjects who are lactating must discontinue nursing prior to the first dose of study treatment and must refrain from nursing throughout the treatment period and for 5 half-lives of GSK525762 or at least 28 days (whichever is longer) following the last dose of study treatment.
* Male subjects must agree to use one of the methods of contraception specified. This method must be used from the time of the first dose of study medication until 16 weeks after the last dose of study medication. In addition, male subjects whose partners are or become pregnant must continue to use condoms for 7 days after stopping study medications.
* Adequate organ system function.
* Ability to comply with dietary and tobacco/alcohol abstinence requirements.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Exclusion Criteria

* 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] Ribonucleic acid [RNA]).
* 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.
* Currently receiving cancer therapy (chemotherapy, radiation therapy, immuno- therapy, biologic therapy, hormonal therapy, surgery, and/or tumour embolization).The following are allowed: Hydroxyurea for proliferative disease, Corticosteroids, Use of hematopoetic growth factors 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.). The following are NOT allowed: Investigational anti cancer drug within 2 weeks 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

* Evidence of severe of uncontrolled infection.
* 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.
* 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. In addition, any subject who is expected to require a QT prolonging medication while on trial should not be enrolled.
* 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.
* Symptomatic or untreated Central nervous system (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.
* Cardiac abnormalities as evidenced by any of the following: History or current clinically significant uncontrolled arrhythmias or hypertension; Clinically significant conduction abnormalities or arrhythmias, subjects with Bundle Branch Block; Presence of cardiac pacemaker; History or evidence of current >=Class II congestive heart failure as defined by New York Heart Association (NYHA); History of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months.
* Any of the following ECG findings or assessments including: Baseline QTcF interval >=450 milliseconds; Clinically significant ECG assessments should be reviewed by the site cardiologist prior to study entry.
* GSK525762 is a benzodiazepine class molecule. Any serious known immediate or delayed hypersensitivity reaction(s) to GSK525762 or idiosyncrasy to drugs chemically related to the investigational drug.
* Evidence of hemoptysis within the last 7 days.
* History of major gastrointestinal bleeding within the last 3 months or any evidence of active gastrointestinal bleeding excludes the subject.
* Presence of gastrointestinal disease that would significantly affect compound absorption.

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Single group

Other design features

Phase

Phase 2

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

14/05/2014

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

30/04/2020

Sample size

Target

Accrual to date

Final

111

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

GSK Investigational Site - East Melbourne

Recruitment postcode(s) [1]

3002 - East Melbourne

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

Arkansas

Country [2]

United States of America

State/province [2]

Colorado

Country [3]

United States of America

State/province [3]

New York

Country [4]

United States of America

State/province [4]

Pennsylvania

Country [5]

United States of America

State/province [5]

Texas

Country [6]

Korea, Republic of

State/province [6]

Seoul

Country [7]

Spain

State/province [7]

Barcelona

Country [8]

Spain

State/province [8]

Madrid

Country [9]

Spain

State/province [9]

Málaga

Country [10]

Spain

State/province [10]

Salamanca

Country [11]

United Kingdom

State/province [11]

Cambridge

Country [12]

United Kingdom

State/province [12]

London

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

GlaxoSmithKline

Address

Country

Ethics approval

Ethics application status

Summary

Brief summary

This is an open-label repeat dose, multicenter, 2-part study to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) for GSK525762 given once-daily (QD) orally. Part 1 of the study is a dose escalation phase to select the recommended Part 2 dose (RP2D) based on the safety, PK, and PD profiles observed after oral administration of GSK525762. Eligible subjects with select relapsed refractory hematological malignancies (acute myeloid leukemia \[AML\], non-Hodgkin's Lymphoma \[NHL\]and multiple myeloma \[MM\]), will be enrolled in the QD and/or BID dosing cohorts until a MTD is established. Subjects may continue treatment in the study until disease progression, unacceptable toxicity, or withdrawal of consent. . Upon determination of the MTD, twice daily (BID) dosing cohorts may be opened to collect additional safety data and evaluate the preliminary efficacy of GSK525762 administered BID. Part 2 will explore clinical activity at the MTD or RP2D; separate expansion cohorts will be planned for acute myeloid leukemia (AML), non-Hodgkin's Lymphoma (NHL, including an exploratory sub-cohort of subjects with myc and B-Cell Leukemia (BCL)2 and/or BCL6 rearrangements/overexpression \[double- and triple-hit lymphoma\]), and multiple myeloma (MM). This is the first study of this agent to be conducted in subjects with these relapsed and/or refractory hematological malignancies for which no standard therapies are anticipated to result in a durable remission.

Trial website

https://clinicaltrials.gov/study/NCT01943851

Trial related presentations / publications

Bell C; Fennell K; Chan YC; Rambow F; Yeung M; Vassiliadis D; Lara L; Yeh P; Martelotto L; Rogiers A; Kremer B; Barbash O; Mohammad H; Johanson T; Burr M; Dhar A; Karpinich N; Tian L; Tyler D; MacPherson L; Shi J; Pinnawala N; Fong CY; Papenfuss A; Grimmond S; Dawson SJ; Allan R; Kruger R; Vakoc C; Goode D; Naik S; Gilan O; Lam E; Marine JC; Prinjha R; and Dawson M.Enhancer remodeling overcomes therapeutic resistance driven by epigenetic evolution in cancer.Nature.2019;
Dawson MA, Borthakur G, Huntly BJP, Karadimitris A, Alegre A, Chaidos A, Vogl DT, Pollyea DA, Davies FE, Morgan GJ, Glass JL, Kamdar M, Mateos MV, Tovar N, Yeh P, Delgado RG, Basheer F, Marando L, Gallipoli P, Wyce A, Krishnatry AS, Barbash O, Bakirtzi E, Ferron-Brady G, Karpinich NO, McCabe MT, Foley SW, Horner T, Dhar A, Kremer BE, Dickinson M. A Phase I/II Open-Label Study of Molibresib for the Treatment of Relapsed/Refractory Hematologic Malignancies. Clin Cancer Res. 2023 Feb 16;29(4):711-722. doi: 10.1158/1078-0432.CCR-22-1284.

Public notes

Contacts

Principal investigator

Name

GSK Clinical Trials

Address

GlaxoSmithKline

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

GSK will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)

When will data be available (start and end dates)?

Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.

Available to whom?

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Available for what types of analyses?

How or where can data be obtained?

IPD available at link: https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf

What supporting documents are/will be available?

Type	Other Details	Attachment
Study protocol		https://cdn.clinicaltrials.gov/large-docs/51/NCT01943851/Prot_000.pdf
Statistical analysis plan		https://cdn.clinicaltrials.gov/large-docs/51/NCT01943851/SAP_001.pdf

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01943851

Additional trial details provided through ANZCTR

Accrual to date

Recruiting in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Primary sponsor

Commercial sector/Industry

Primary sponsor name

GlaxoSmithKline

Primary sponsor address

Primary sponsor country

Ethics approval

Ethics application status

Approved

Public notes

Contacts

Principal investigator

Title

Prof

Name

Mark Dawson

Address

Peter MacCallum Cancer Center, Melbourne VIC 3000

Country

Australia

Phone

Fax

Contact person for public queries

Title

Name

Address

Country

Phone

Fax

GSKClinicalSupportHD@gsk.com

Contact person for scientific queries

Title

Name

Address

Country

Phone

Fax

GSKClinicalSupportHD@gsk.com

Register a trial

Registering a new trial?

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01943851