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A Study to Assess AMG 701 Montherapy, or in Combination With Pomalidomide, With or Without, Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03287908
Recruitment Status : Recruiting
First Posted : September 19, 2017
Last Update Posted : September 21, 2020
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
The primary purpose of the phase 1 part of the study is to evaluate safety and tolerability of AMG 701 monotherapy to identify the RP2D for AMG 701 monotherapy followed by a dose-confirmation part to gather further safety data for AMG 701 monotherapy at the RP2D in adult subjects with relapsed/refractory multiple myeloma (RRMM). In addition, this study will include a sequential dose exploration part to identify the RP2D of AMG 701 in combination with pomalidomide, with and without dexamethasone (AMG 701-P+/-d). Phase 2 will consist of the dose-expansion part to gain further efficacy and safety experience with AMG 701 monotherapy in adult subjects with RRMM.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Multiple Myeloma Drug: AMG 701 Drug: Pomalidomide Drug: Dexamethasone Phase 1

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Study Type : Interventional
Estimated Enrollment : 344 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : November 13, 2017
Estimated Primary Completion Date : January 30, 2023
Estimated Study Completion Date : September 1, 2026


Arm Intervention/treatment
Experimental: AMG 701 Drug: AMG 701
Subjects will receive IV infusions of AMG 701.

Experimental: AMG 701 + Pomalidomide Drug: AMG 701
Subjects will receive IV infusions of AMG 701.

Drug: Pomalidomide
Subjects will receive oral capsules of pomalidomide.

Experimental: AMG 701 + Pomalidomide + Dexamethasone Drug: AMG 701
Subjects will receive IV infusions of AMG 701.

Drug: Pomalidomide
Subjects will receive oral capsules of pomalidomide.

Drug: Dexamethasone
Subjects will receive IV injections or oral dexamethasone.




Primary Outcome Measures :
  1. Number of subjects with dose-limiting toxicities (DLTs) [ Time Frame: 28 days ]
  2. Number of subjects with treatment emergent adverse events (TEAEs) [ Time Frame: 60 months ]
  3. Number of subjects with treatment-related adverse events [ Time Frame: 60 months ]
  4. Number of subjects with disease-related adverse events [ Time Frame: 60 months ]
  5. Number of subjects with clinically-significant changes in vital signs [ Time Frame: 48 months ]
  6. Number of subjects with clinically-significant changes in physical examination measurements [ Time Frame: 48 months ]
  7. Number of subjects with clinically-significant changes in electrocardiogram (ECG) measurements [ Time Frame: 48 months ]
  8. Number of subjects with clinically-significant changes in clinical laboratory tests [ Time Frame: 48 months ]

Secondary Outcome Measures :
  1. Pharmacokinetic parameter of AMG 701: Maximum concentration (Cmax) [ Time Frame: 12 weeks ]
  2. Pharmacokinetic parameter of AMG 701: Time of maximum concentration (Tmax) [ Time Frame: 12 weeks ]
  3. Pharmacokinetic parameter of AMG 701: Area under the concentration-time curve (AUC) [ Time Frame: 12 weeks ]
  4. Pharmacokinetic parameter of AMG 701: Steady state concentration (Css) [ Time Frame: 12 weeks ]
  5. Anti-tumor activity: Overall response rate [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria. Best overall response of stringent CR (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).

  6. Anti-tumor activity: Best overall response of stringent complete response (sCR) [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.

  7. Anti-tumor activity: Best overall response of complete response (CR) [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.

  8. Anti-tumor activity: Best overall response of very good partial response (VGPR) [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.

  9. Anti-tumor activity: Best overall response of partial response (PR) [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.

  10. Anti-tumor activity: Duration of response [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria. Defined as time from the first PR or better to disease progression or death.

  11. Anti-tumor activity: Time to response [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.

  12. Anti-tumor activity: Progression-free survival [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria. Defined as time from start of treatment until disease progression or death.

  13. Anti-tumor activity: Overall survival [ Time Frame: 60 months ]
    Defined as time from start of treatment until death due to any cause.

  14. Anti-tumor activity: Number of subjects with minimum residual disease negative complete response [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.

  15. Pharmacokinetic parameter of AMG 701: Trough concentration (Ctrough) [ Time Frame: 12 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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).

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03287908


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
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United States, Arizona
Research Site Recruiting
Phoenix, Arizona, United States, 85054
United States, Arkansas
Research Site Recruiting
Little Rock, Arkansas, United States, 72205
United States, Florida
Research Site Recruiting
Jacksonville, Florida, United States, 32224
United States, Georgia
Research Site Recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
Research Site Recruiting
Chicago, Illinois, United States, 60637
United States, Minnesota
Research Site Recruiting
Rochester, Minnesota, United States, 55905
United States, Missouri
Research Site Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Research Site Recruiting
New York, New York, United States, 10029
Research Site Recruiting
New York, New York, United States, 10032
Research Site Recruiting
New York, New York, United States, 10065
United States, North Carolina
Research Site Recruiting
Charlotte, North Carolina, United States, 28204
United States, Texas
Research Site Recruiting
Houston, Texas, United States, 77030
United States, Utah
Research Site Recruiting
Salt Lake City, Utah, United States, 84112
United States, Wisconsin
Research Site Recruiting
Milwaukee, Wisconsin, United States, 53226
Australia, Victoria
Research Site Recruiting
Melbourne, Victoria, Australia, 3000
Research Site Recruiting
Melbourne, Victoria, Australia, 3004
Germany
Research Site Recruiting
Heidelberg, Germany, 69120
Research Site Recruiting
Kiel, Germany, 24105
Japan
Research Site Recruiting
Nagoya-shi, Aichi, Japan, 467-8602
Research Site Recruiting
Maebashi-shi, Gunma, Japan, 371-8511
Netherlands
Research Site Recruiting
Groningen, Netherlands, 9713 GZ
Research Site Recruiting
Utrecht, Netherlands, 3584 CX
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03287908    
Other Study ID Numbers: 20170122
2017-001997-41 ( EudraCT Number )
First Posted: September 19, 2017    Key Record Dates
Last Update Posted: September 21, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: 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.
Access Criteria: 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.
URL: https://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Amgen
Phase 1
Phase 2
Phase 1/2
Clinical Trial
Oncology/Hematology
Relapsed/Refractory Multiple Myeloma
Immunotherapy
Additional relevant MeSH terms:
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Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Multiple Myeloma
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Pomalidomide
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents