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Relapsed and/or Refractory Multiple MyelomaPhase 1/2NCT03715478

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

A Phase 1/2 study testing GSK2857916 with Pomalidomide and Dexamethasone in people with Relapsed and/or Refractory Multiple Myeloma, run by Canadian Myeloma Research Group at 9 sites in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

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

Who is it for?
Ages 18 years and older
What is being tested?
GSK2857916 with Pomalidomide and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
9 sitesCanada
Study dates
26 Nov 2018to 31 Dec 2027
Phase
Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Must be able to understand and voluntarily sign an informed consent form (ICF).
  • Must be ≥ 18 years of age at the time of signing the ICF.
  • Must be able to adhere to the study visit schedule and other protocol requirements.
  • 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). Induction therapy followed by ASCT and consolidation/maintenance will be considered as one line.
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  • 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).
  • 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
  • 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)
  • Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
  • 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.
  • 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.
  • 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.
  • Must be registered into the mandatory RevAid® program and be willing and able to comply with the requirements of the RevAid® program.
  • Able to take oral medications.
  • 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).
  • The following laboratory results must be met within 10 days of first study drug administration:
  • Absolute neutrophil count (ANC) > 1.0 x 109/L. G-CSF cannot be given within 10 days prior to screening.
  • 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.

Who cannot join

  • Prior pomalidomide or BCMA therapy use.
  • History of allegeneic transplant
  • 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.
  • Pregnant or lactating females.
  • 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.
  • 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).
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  • Evidence of cardiovascular risk including any of the following:
  • QTc interval ≥ 470 msecs. NOTE: The QT interval should be corrected for the heart rate by Fridericia's formula (QTcF)
  • Evidence of current clinically significant uncontrolled arrhythmias; including clinically significant ECG abnormalities; including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
  • History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening.
  • Class III or IV heart failure as defined by the New York Heart Association functional classification system (Appendix 3)
  • Uncontrolled hypertension
  • 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. Participants with positive hepatitis B core antibody (HBcAb) can be enrolled, only if confirmatory negative Hepatitis B DNA is obtained AND patient is on hepatitis B prophylaxis (tenofovir or entecavir) before first dose of study drug.
  • 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.
  • 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.
  • Current corneal epithelial disease except for mild punctate keratopathy (mild punctate keratopathy is allowed).
  • Known active infection requiring antibiotic, anti-viral or anti-fungal treatment.
  • Evidence of active mucosal or internal bleeding.
  • Hypersensitivity to thalidomide, lenalidomide (such as Steven Johnson Syndrome) or intolerance to dexamethasone. Hypersensitivity, such as rash, that can be medically managed is allowable.
  • Peripheral neuropathy ≥ Grade 2 despite supportive therapy.
  • 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.
  • 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.
  • Any major surgery within the last 4 weeks.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2857916 or any of the components of the study treatment.
  • Intolerance to prednisone or dexamethasone that would preclude the patient from taking the full starting dose of dexamethasone as described in the protocol (Section 6.2).

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Canada9 sites

  • Cross Cancer Institute

    Edmonton, Alberta

  • QEII Health Sciences Centre

    Halifax, Nova Scotia

  • Juravinski Cancer Centre

    Hamilton, Ontario

  • London Health Sciences Centre

    London, Ontario

  • The Ottawa Hospital

    Ottawa, Ontario

  • Allan Blair Cancer Centre

    Regina, Saskatchewan

  • Princess Margaret Cancer Centre

    Toronto, Ontario

  • Vancouver General Hospital

    Vancouver, British Columbia

  • CancerCare Manitoba

    Winnipeg, Manitoba

Other trials in Canada

About this study

Official title: 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

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

Read the 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 IV GSK2857916 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 dose-finding portion and a Part 2 expansion phase. Part 1 will determine the starting dose and schedule to be used in Part 2. All subjects will receive GSK2857916 given IV either on Day 1 (Single Dose) or on Days 1 and 8 (Split Dose) 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 1 portion of the study will determine the MTD and/or RP2D and dose limiting toxicities (DLTs) of GSK2857916 administered 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 either Single Dose (dose level 1a) or Split Dose (dose level 1b), 1.92 mg/kg Single Dose (dose level -1), and 3.4 mg/kg Split Dose (dose level 2). 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. 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.

Being tested
GSK2857916 with Pomalidomide and Dexamethasone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK2857916 with Pomalidomide and DexamethasoneDrug

    Also called Pomalyst

    Recommended phase 2 dose (RP2D) 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.

Study groups in NCT03715478
Study groupRoleWhat they receive
GSK2857916 with Pomalidomide and DexamethasoneExperimentalThis will be a single arm study of GSK2857916 administered with pomalidomide and dexamethasone. GSK2857916 will be administered intravenously either on Day 1 of each 28 day cycle (Single Dose) or on Days 1 and 8 (Split Dose) and up to 4 dose levels will be evaluated during the phase I portion. Pomalidomide will be administered orally on Days 1-21 at 4 mg. Dexamethasone will be administered orally at 40 mg for patients ≤ 75 years old or 20 mg for patients older than 75 on days 1, 8, 15, 22.
Receives: Drug: GSK2857916 with Pomalidomide and Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recommended Phase 2 Dose (RP2D)

    RP2D and schedule of GSK2857916 for Part 2 will be determined by Part 1 of the study

    Measured: 9 months

  2. Overall Response Rate (ORR)

    Overall response rate will be the percentage of patients achieving partial response or better according to IMWG response criteria

    Measured: 60 months

Secondary outcomes (3)

  1. Treatment Emergent Adverse Events

    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

    Measured: 60 months

  2. Progression Free Survival

    Progression Free Survival according to IMWG criteria will be evaluated

    Measured: 60 months

  3. Maximum tolerated dose (MTD)

    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)

    Measured: 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Oct 2018
  2. Study start26 Nov 2018
  3. Primary completion1 Jun 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03715478
Sponsor's protocol ID
CMRG 007
Other IDs
ALGONQUIN
Status last verified
Oct 2026
First submitted
2 Oct 2018
Last updated
22 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Trudel S, McCurdy A, Louzada ML, Parkin S, White D, Chu MP, Kotb R, Mian H, Othman I, Su J, Khan A, Gul E, Reece D. Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1/2 trial. Nat Med. 2024 Feb;30(2):543-551. doi: 10.1038/s41591-023-02703-y. Epub 2024 Jan 4.

    PubMed 38177852

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