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Trial record 34 of 45 for:    thalidomide myeloma | Recruiting, Not yet recruiting, Available Studies

Multi-Center Study of GSK2857916 in Combination With Pomalidomide and Dex

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ClinicalTrials.gov Identifier: NCT03715478
Recruitment Status : Recruiting
First Posted : October 23, 2018
Last Update Posted : July 29, 2019
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Myeloma Canada Research Network

Tracking Information
First Submitted Date  ICMJE October 2, 2018
First Posted Date  ICMJE October 23, 2018
Last Update Posted Date July 29, 2019
Actual Study Start Date  ICMJE November 26, 2018
Estimated Primary Completion Date June 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2018)
  • Maximum tolerated dose (MTD) [ Time Frame: 9 months ]
    Adverse Events occurring during the first cycle of study treatment will be evaluated against a predefined dose limiting toxicities to determine the maximally tolerated dose (MTD)
  • Overall Response Rate (ORR) [ Time Frame: 60 months ]
    Overall response rate will be the percentage of patients achieving partial response or better according to IMWG response criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03715478 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2018)
  • Treatment Emergent Adverse Events [ Time Frame: 60 months ]
    Treatment Emergent Adverse Events occurring during the study will be evaluated according to CTCAE version 5.0 to determine the safety of the study treatment
  • Progression Free Survival [ Time Frame: 60 months ]
    Progression Free Survival according to IMWG criteria will be evaluated
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Multi-Center Study of GSK2857916 in Combination With Pomalidomide and Dex
Official Title  ICMJE A Phase 1/2 Multi-Center, Open Label, Dose Escalation Study to Determine the RP2D, Safety and Efficacy of GSK2857916 in Combination With Pomalidomide and Low-Dose Dexamethasone in Subjects With Relapsed and/or Refractory Multiple Myeloma
Brief Summary This is a Phase 1/2, multi-centre, single-arm, open-label, dose-escalation study that will evaluate the safety and efficacy of GSK2857916 given IV q 4 weeks in combination with PO pomalidomide and low-dose PO dexamethasone in subjects with relapsed and/or refractory MM.
Detailed Description

This is a Phase 1/2, multi-centre, single-arm, open-label, dose-escalation study that will evaluate the safety and efficacy of GSK2857916 given IV q 4 weeks in combination with PO pomalidomide and low-dose PO dexamethasone in subjects with relapsed and/or refractory MM.

This study will consist of a Part 1 GSK2857916, pomalidomide and low dose dexamethasone dose-finding portion and a Part 2 expansion phase. The Part 1 part will determine the starting dose and schedule to be used in the Part 2 segment of the study. All subjects will receive GSK2857916 given IV q 4 weeks in combination with pomalidomide and dexamethasone administered orally in 28-day treatment cycles. Treatment will be administered as long as there is clinical benefit.

The Part I portion of the study will determine the MTD and/or RP2D and dose limiting toxicities (DLTs) of GSK2857916 administered IV q 4 weeks in combination with pomalidomide and dexamethasone. The following dose levels of GSK2857916 in combination with 4 mg of pomalidomide and low-dose dexamethasone are to be tested in this study: 2.5 mg/kg (dose level 1) and 3.4 mg/kg (dose level 2). An additional lower dose level of 1.92 mg/kg (dose level -1) maybe tested if 2 or more DLTs are observed in dose level 1. The Part 1 segment of the study will follow a standard 3 + 3 dose escalation design and will include assessment of the safety of treatment between each dose cohort by the Safety Review Committee (SRC) consisting of the Study Investigators and the Sponsor.

When the SRC has determined the RP2D of GSK2857916, the Part 2 portion of the study will be initiated. Pomalidomide will be administered based on the current approved dose and schedule: 4 mg PO QD on Days 1 to 21 of a 28-day cycle. The starting dose of dexamethasone will be 40 mg QD on Days 1, 8, 15 and 22 of each 28-day cycle for subjects who are ≤ 75 years of age. For Subjects who are > 75 years of age, the starting dose of dexamethasone is 20 mg QD on Days 1, 8, 15, and 22 of each 28-day cycle. GSK2857916 will be administered at the RP2D and treatment will continue until progressive disease (PD) or toxicity requiring discontinuation of study drug. Efficacy assessments will be conducted every cycle for the duration of the treatment period. After discontinuation from treatment, follow up will continue by phone or in person until progression from the next line of treatment or death to a maximum of 36 months after enrolment for determination of PFS2 and OS.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed and/or Refractory Multiple Myeloma
Intervention  ICMJE Drug: GSK2857916 with Pomalidomide and Dexamethasone
Recommended phase 2 dose of GSK2857916 determined by the phase 1 portion of study will be administered in combination with pomalidomide (approved dose and schedule) and dexamethasone until progression of disease.
Other Name: Pomalyst
Study Arms  ICMJE Experimental: GSK2857916 with Pomalidomide and Dexamethasone
This will be a single arm study of GSK2857916 administered with pomalidomide and dexamethasone. GSK2857916 will be administered IV q 4 weeks for each 28 day cycle while pomalidomide will be administered orally on days 1-21 at 4 mg. Dexamethasone will be administered at 40 for patients 75 years old or younger or 20 mg for patients older than 75 on days 1, 8, 15, 22.
Intervention: Drug: GSK2857916 with Pomalidomide and Dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 19, 2018)
52
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2024
Estimated Primary Completion Date June 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Must be able to understand and voluntarily sign an informed consent form (ICF).
  2. Must be ≥ 18 years of age at the time of signing the ICF.
  3. Must be able to adhere to the study visit schedule and other protocol requirements.
  4. Documented diagnosis of MM and relapsed and/or refractory disease with:

    • Have undergone stem cell transplant, or have been considered transplant ineligible
    • Previously treated with two or more prior lines of treatment that must have included lenalidomide and a proteasome inhibitor (in separate regimens or in combination)
    • Documented evidence of progressive disease (PD) after achieving at least stable disease (SD) for ≥ 1 cycle during a previous MM treatment (i.e., relapsed MM) and/or
    • Disease progression during or within 60 days from the end of the most recent MM treatment (i.e., refractory MM).
  5. Subjects with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met:

    • transplant was > 100 days prior to study enrolment
    • no active infection
  6. Subjects with measurable disease defined as at least one of the following (these baseline laboratory studies for determining eligibility must be obtained within 28 days prior to start of study drug):

    • Serum M-protein ≥ 5 g/l
    • Urine M-protein ≥ 200 mg/24 h
    • Serum free light chains (FLC) assay: Involved FLC level ≥ 100 mg/l and an abnormal serum free light chain ratio (< 0.26 or > 1.65)
  7. Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
  8. Females of child-bearing potential (FCBP) must have two negative serum pregnancy test, as described in Appendix 1 for the RevAid® program. FCBP and males must either commit to continued abstinence from heterosexual intercourse or must abide by birth control requirements 120 days post discontinuation of treatment as described in Appendix 1 for the RevAid® program.
  9. Men with a female partner and females of childbearing potential must agree to use effective contraception as described in Appendix 1 from the time of first dose of study until 120 days (females) and 140 days after the last dose of study treatment to allow for clearance of any altered sperm.
  10. Must be able to take acetylsalicylic acid (ASA) (81 or 325 mg) daily as prophylactic anticoagulation. Subjects intolerant to ASA may use low molecular weight heparin or alternative anticoagulant.
  11. Must be registered into the mandatory RevAid® program and be willing and able to comply with the requirements of the RevAid® program.
  12. Able to take oral medications.
  13. All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0) must be ≤Grade 1 at the time of enrollment except for alopecia or be deemed to be irreversible (for example, steroid induced cataracts).
  14. The following laboratory results must be met within 10 days of first study drug administration:

    • Absolute neutrophil count (ANC) > 1.0 x 109/L. Growth factors cannot be given within 10 days of study drug administration.
    • Serum ALT ≤ 2.5 x upper limits of normal (ULN).
    • eGFR (MDRD) ≥ 40 mL/min (Appendix 2).
    • Platelet count > 75 x 109/L. Platelet transfusions to help subjects meet eligibility criteria are not allowed within 10 days before study enrolment.
    • Hemoglobin ≥ 80 g/L.
    • Total bilirubin ≤ 1.5 x ULN, unless known to have Gilbert's disease. If Gilberts, isolated bilirubin > 1.5 and < 3xULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%.
    • Albumin/creatinine ratios (spot urine) <500mg/g (56 mg/mmol)
    • Albumin ≥ 20 g/L.

Exclusion Criteria:

  1. Prior pomalidomide use.
  2. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
  3. Pregnant or lactating females.
  4. Subjects with previous or concurrent malignancies are allowed only if the second tumor is not contributing to the subject's illness. The subject must not be receiving active therapy, other than hormonal therapy for this disease and the disease must be considered medically stable for at least 2 years.
  5. Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect subject's safety). Subjects with isolated proteinuria resulting from MM are eligible, provided they fulfil criteria given in inclusion criteria (i.e. albumin/creatinine < 500 mg/ g (56 mg/mmol).
  6. Evidence of cardiovascular risk including any of the following:

    1. QTc interval ≥ 470 msecs. NOTE: The QT interval should be corrected for the heart rate by Fridericia's formula (QTcF)
    2. Evidence of current clinically significant uncontrolled arrhythmias; including clinically significant ECG abnormalities; including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
    3. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening.
    4. Class III or IV heart failure as defined by the New York Heart Association functional classification system (Appendix 34)
    5. Uncontrolled hypertension
  7. Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb at screening or within 3 months prior to first dose of study treatment
  8. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment. Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Note: Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.
  9. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria.
  10. Current corneal epithelial disease except for mild punctate keratopathy (mild punctate keratopathy is allowed).
  11. Known active infection requiring antibiotic, anti-viral or anti-fungal treatment.
  12. Evidence of active mucosal or internal bleeding.
  13. Hypersensitivity to thalidomide, lenalidomide (such as Steven Johnson Syndrome) or intolerance to dexamethasone. Hypersensitivity, such as rash, that can be medically managed is allowable.
  14. Peripheral neuropathy ≥ Grade 2 despite supportive therapy.
  15. Radiotherapy (with the exception of local, palliative radiotherapy for management of pain) or systemic therapy (standard or biologic anticancer agent) within 14 days of initiation of study drug treatment.
  16. Use of an investigational drug within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drug.
  17. Any major surgery within the last 4 weeks.
  18. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2857916 or any of the components of the study treatment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Julia Dobbin 289-378-6513 jdobbin@mcrn.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03715478
Other Study ID Numbers  ICMJE MCRN 007
ALGONQUIN ( Other Identifier: MCRN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Myeloma Canada Research Network
Study Sponsor  ICMJE Myeloma Canada Research Network
Collaborators  ICMJE GlaxoSmithKline
Investigators  ICMJE Not Provided
PRS Account Myeloma Canada Research Network
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP