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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03287908




Registration number
NCT03287908
Ethics application status
Date submitted
6/09/2017
Date registered
19/09/2017

Titles & IDs
Public title
A Study to Assess AMG 701 Montherapy, or in Combination With Pomalidomide, With or Without, Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Scientific title
A Phase 1/2 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 701 Monotherapy, or in Combination With Pomalidomide, With and Without Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (ParadigMM-1B)
Secondary ID [1] 0 0
2017-001997-41
Secondary ID [2] 0 0
20170122
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG 701
Treatment: Drugs - Pomalidomide
Treatment: Drugs - Dexamethasone

Experimental: AMG 701 -

Experimental: AMG 701 + Pomalidomide -

Experimental: AMG 701 + Pomalidomide + Dexamethasone -


Treatment: Drugs: AMG 701
Subjects will receive IV infusions of AMG 701.

Treatment: Drugs: Pomalidomide
Subjects will receive oral capsules of pomalidomide.

Treatment: Drugs: Dexamethasone
Subjects will receive IV injections or oral dexamethasone.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects with dose-limiting toxicities (DLTs)
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Number of subjects with treatment emergent adverse events (TEAEs)
Timepoint [2] 0 0
60 months
Primary outcome [3] 0 0
Number of subjects with treatment-related adverse events
Timepoint [3] 0 0
60 months
Primary outcome [4] 0 0
Number of subjects with disease-related adverse events
Timepoint [4] 0 0
60 months
Primary outcome [5] 0 0
Number of subjects with clinically-significant changes in vital signs
Timepoint [5] 0 0
48 months
Primary outcome [6] 0 0
Number of subjects with clinically-significant changes in physical examination measurements
Timepoint [6] 0 0
48 months
Primary outcome [7] 0 0
Number of subjects with clinically-significant changes in electrocardiogram (ECG) measurements
Timepoint [7] 0 0
48 months
Primary outcome [8] 0 0
Number of subjects with clinically-significant changes in clinical laboratory tests
Timepoint [8] 0 0
48 months
Secondary outcome [1] 0 0
Pharmacokinetic parameter of AMG 701: Maximum concentration (Cmax)
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
Pharmacokinetic parameter of AMG 701: Time of maximum concentration (Tmax)
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
Pharmacokinetic parameter of AMG 701: Area under the concentration-time curve (AUC)
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
Pharmacokinetic parameter of AMG 701: Steady state concentration (Css)
Timepoint [4] 0 0
12 weeks
Secondary outcome [5] 0 0
Anti-tumor activity: Overall response rate
Timepoint [5] 0 0
48 months
Secondary outcome [6] 0 0
Anti-tumor activity: Best overall response of stringent complete response (sCR)
Timepoint [6] 0 0
48 months
Secondary outcome [7] 0 0
Anti-tumor activity: Best overall response of complete response (CR)
Timepoint [7] 0 0
48 months
Secondary outcome [8] 0 0
Anti-tumor activity: Best overall response of very good partial response (VGPR)
Timepoint [8] 0 0
48 months
Secondary outcome [9] 0 0
Anti-tumor activity: Best overall response of partial response (PR)
Timepoint [9] 0 0
48 months
Secondary outcome [10] 0 0
Anti-tumor activity: Duration of response
Timepoint [10] 0 0
48 months
Secondary outcome [11] 0 0
Anti-tumor activity: Time to response
Timepoint [11] 0 0
48 months
Secondary outcome [12] 0 0
Anti-tumor activity: Progression-free survival
Timepoint [12] 0 0
48 months
Secondary outcome [13] 0 0
Anti-tumor activity: Overall survival
Timepoint [13] 0 0
60 months
Secondary outcome [14] 0 0
Anti-tumor activity: Number of subjects with minimum residual disease negative complete response
Timepoint [14] 0 0
48 months
Secondary outcome [15] 0 0
Pharmacokinetic parameter of AMG 701: Trough concentration (Ctrough)
Timepoint [15] 0 0
12 weeks

Eligibility
Key inclusion criteria
* Multiple myeloma meeting the following criteria:

* Pathologically-documented diagnosis of multiple myeloma that is relapsed or is refractory as defined by the following:

* Relapsed after > or = 3 lines of prior therapy that must include all approved and available therapies deemed eligible by the investigator, inclusing at a minimum of a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and, where approved and available, a CD38-directed cytolytic antibody in combination in the same line or separate lines of treatment OR refractory to PI, IMiD, and CD38- directed cytolytic antibody,
* Subjects who could not tolerate a PI, IMiDs, or a CD38-directed cytolytic antibody are eligible to enroll in the study.
* Measurable disease as per IMWG response criteria
* Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2

Inclusion criteria specific to AMG 701-P±d include:

* Subjects must have received = 2 lines of prior therapy that must include a proteasome inhibitor (PI), lenalidomide, and where approved and available a CD38-directed antibody. These therapies may be in the same line or separate lines of treatment.
* Subjects must have responded to at least 1 prior line with at least a PR.
* Subjects that have previously received pomalidomide must not have been removed from therapy due to toxicity attributable to pomalidomide and must be at least 6 months from their last dose of pomalidomide.
* Subjects must not have known intolerance to doses of dexamethasone up to 40 mg weekly (20 mg weekly if > 75 years).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Known extramedullary relapse in the absence of any measurable medullary involvement
* Known central nervous system involvement by multiple myeloma
* Autologous stem cell transplantation less than 90 days prior to study day 1
* Recent history of primary plasma cell leukemia (within last 6 months prior to enrollment) or evidence of primary or secondary plasma cell leukemia at the time of screening
* Waldenstrom's macroglobulinemia
* Prior amyloidosis (subjects with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met)
* Treatment with systemic immune modulators including, but not limited to, nontopical systemic corticosteroids (unless the dose is = 10 mg/day prednisone or equivalent), cyclosporine, and tacrolimus within 2 weeks before study day 1
* Last anticancer treatment (chemotherapy, IMiD, PI, molecular targeted therapy) < 2 weeks prior to study day 1 or treatment with a therapeutic antibody less than 4 weeks prior to study day 1 as well as systemic radiation therapy within 28 days prior to study day 1 or focal radiotherapy within 14 days prior to study day 1.
* Prior treatment with any drug or construct that targets BCMA on tumor cells (eg, other bispecific antibody constructs, antibody drug conjugates, or CAR-T cells), other than Group C where prior treatment with GSK2857916 (belantamab mafodotin) is required.

Exclusion criteria specific to AMG 701-P±d include:

* History of serious hypersensitivity associated with thalidomide, pomalidomide, or lenalidomide (> grade 3).
* Multiple myeloma with IgM subtype.
* POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
* Contraindication to pomalidomide or dexamethasone.
* Glucocorticoid therapy within 14 days prior to randomization that exceeds a cumulative dose of 160 mg of dexamethasone or equivalent dose of other corticosteroids.
* Treatment with systemic immune modulators including, but not limited to, non-topical systemic corticosteroids (unless the dose is = 10 mg/day prednisone or equivalent), cyclosporine, and tacrolimus within 2 weeks before study day 1 or 4 weeks before study day 1 for Phase 1 dose-confirmation.
* Female subjects of childbearing potential with a positive pregnancy test assessed within 14 days prior to first dose of study drugs and/or a positive urine pregnancy test within 24 hours prior to first dose. In addition, females of childbearing potential unwilling to undergo pregnancy testing weekly during the first 4 weeks of pomalidomide use followed by pregnancy testing every 4 weeks in females with regular menses or every 2 weeks in females with irregular menstrual cycles.
* Male subjects with a female partner of childbearing potential and female subjects of childbearing potential who are unwilling to use 2 methods of contraception (1 of which must be highly effective during the study and for an additional 75 days (females) and 135 days (males) after receiving the last dose of AMG 701, or 28 days after the last dose pomalidomide (males and females) or dexamethasone (females), whichever occurs later.
* Females who are lactating/breastfeeding or who plan to breastfeed while on study through 75 days after receiving the last dose of AMG 701, or 28 days after the last dose pomalidomide or dexamethasone, whichever occurs later.
* Females planning to become pregnant while on study through 75 days after receiving the last dose of AMG 701 or 28 days after the last dose pomalidomide or dexamethasone, whichever occurs later.
* Male subjects with a pregnant partner who are unwilling to practice abstinence or use a latex or synthetic condom (even if they have had a vasectomy with medical confirmation of surgical success) during treatment (including during dose interruptions) and for an additional 135 days after the last dose of AMG 701, or 28 days after the last dose pomalidomide, whichever occurs later.
* Males who are unwilling to abstain from sperm donation while on study through 135 days after receiving the last dose of AMG 701 or 28 days after the last dose pomalidomide, whichever occurs later.

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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/11/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/06/2023
Sample size
Target
Accrual to date
Final
174
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [3] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Wisconsin
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Germany
State/province [17] 0 0
Heidelberg
Country [18] 0 0
Germany
State/province [18] 0 0
Kiel
Country [19] 0 0
Germany
State/province [19] 0 0
Wuerzburg
Country [20] 0 0
Japan
State/province [20] 0 0
Aichi
Country [21] 0 0
Japan
State/province [21] 0 0
Gunma
Country [22] 0 0
Japan
State/province [22] 0 0
Hyogo
Country [23] 0 0
Japan
State/province [23] 0 0
Ishikawa
Country [24] 0 0
Japan
State/province [24] 0 0
Okayama
Country [25] 0 0
Japan
State/province [25] 0 0
Tokyo
Country [26] 0 0
Netherlands
State/province [26] 0 0
Groningen
Country [27] 0 0
Netherlands
State/province [27] 0 0
Maastricht
Country [28] 0 0
Netherlands
State/province [28] 0 0
Utrecht

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
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?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

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)?
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Available to whom?
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03287908