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Study of Early Relapsed, Lenalidomide-refractory Subjects Eligible for Carfilzomib Triplet (SELECT)

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: NCT04191616
Recruitment Status : Not yet recruiting
First Posted : December 10, 2019
Last Update Posted : July 22, 2020
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
A Study Evaluating Treatment of Multiple Myeloma with Carfilzomib in Combination with Pomalidomide and Dexamethasone

Condition or disease Intervention/treatment Phase
Relapsed or Refractory Multiple Myeloma Drug: Carfilzomib Drug: Dexamethasone Drug: Pomalidomide Phase 2

Detailed Description:

An Open-label, Phase 2 Study Treating Subjects with First or Second Relapse of Multiple Myeloma with Carfilzomib, Pomalidomide, and Dexamethasone (KPd)

This trial is designed to estimate the efficacy of a carfilzomib-based triplet in first or second relapse of multiple myeloma for subjects refractory to lenalidomide and exposed to daratumumab The study is an open-label, phase 2 trial. Approximately 85 subjects will be enrolled in the study. Subjects may receive treatment until progression.

Myeloma disease status will be monitored locally for response and progression per International Myeloma Working Group (IMWG) criteria (Kumar et al, 2016) every 28 ± 7 days from cycle 1 day 1 until confirmed progressive disease (PD), death, lost to follow-up, or withdrawal of full consent (whichever occurs first), regardless of cycle duration, dose delays or treatment discontinuation. Subjects with a suspected complete response (CR) or better will have a bone marrow for minimal residual disease (MRD) assessment at 12 and 24 months (± 4 weeks) from start of treatment (unless a MRD assessment was performed within 4 months before planned assessment).

Subjects who end study drug(s) without confirmed PD are required to complete disease response assessments and report new anti-myeloma treatment every 28 ± 7 days until first subsequent anti-myeloma treatment, death, lost to follow-up, withdrawal of full consent, confirmed PD, or end of study, whichever occurs first. Subjects who discontinue treatment and either start new antimyeloma treatment or have PD will enter long-term follow-up every 12 weeks until death or end of study.

Approximately 85 subjects will be enrolled in the study, with approximately one-third of subjects in first relapse and two-thirds in second relapse.

This study will enroll adults ≥ 18 years of age with first or second relapse multiple myeloma.

Eligible subjects will have relapsed multiple myeloma after receiving 1 or 2 prior lines of therapy.

Subjects must be refractory to lenalidomide and completed at least 2 consecutive cycles of daratumumab.

Subjects may not have received prior pomalidomide. Prior exposure to a proteasome inhibitor is allowed. Subjects previously exposed to carfilzomib must have responded with at least a partial response to carfilzomib, must not have discontinued carfilzomib due to toxicity, may not have relapsed while receiving or within 60 days of the last dose of carfilzomib, and must have at least a 6 month carfilzomib treatment-free interval since their last dose of carfilzomib.

Subjects must have measurable disease per IMWG consensus criteria, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2, and at least partial response (PR) to 1 line of therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 85 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Phase 2 Study Treating Subjects With First or Second Relapse of Multiple Myeloma With Carfilzomib, Pomalidomide, and Dexamethasone (KPd)
Estimated Study Start Date : August 6, 2020
Estimated Primary Completion Date : August 12, 2022
Estimated Study Completion Date : September 11, 2025


Arm Intervention/treatment
Experimental: Carfilzomib combined with pomalidomide and dexamethasone
Carfilzomib, pomalidomide, and dexamethasone (KPd)
Drug: Carfilzomib
Carfilzomib will be administered intravenously over 30 ± 5 minutes, on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression. A dose of 20 mg/m^2 will be administered on day 1 of cycle 1. All subsequent doses will be 56 mg/m^2. The frequency of carfilzomib administration will be reduced to day 1 and 15 per cycle starting with cycle 13 and continued until progression or end of study.
Other Name: Kyprolis

Drug: Dexamethasone
Dexamethasone will be administered at least 30 minutes, but no more than 4 hours prior to carfilzomib on days of carfilzomib administration. Dexamethasone will be administered at a dose of 40 mg on days 1, 8, 15, and 22 of each 28-day cycle up to progression during cycles 1 to 12. Dexamethasone will be administered at a dose of 20 mg on days 1 and 15 of each 28-day cycle up to progression during cycles 13 onward. For subjects more than or equal to 75 years of age, the dose will be 20 mg during cycles 1 through 12 and 10 mg from cycles 13 onward.
Other Name: Decadron, Ozurdex, DexPak 6, 10, 13 Day, ReadySHarp, LoCort, Maxidex

Drug: Pomalidomide
Pomalidomide dose will be 4 mg per day orally on days 1 to 21 of each cycle until progression.
Other Name: Pomalyst




Primary Outcome Measures :
  1. Number of participants with best minimal residual disease negative complete response (MRD[-]CR) [ Time Frame: 12 Months ]
    Best MRD[-]CR response at a sensitive of 10^-5 using next generation sequencing (NGS)-based method in the bone marrow.


Secondary Outcome Measures :
  1. Subject incidence of treatment-emergent adverse event [ Time Frame: Up to 60 Months ]
    Describe the safety and tolerability of carfilzomib combined dexamethasone and pomalidomide.

  2. Number of participants with negative minimal residual disease negative complete response (MRD[-]CR) [ Time Frame: Up to 60 months ]
    MRD[-]CR at a sensitivity of 10^-5 using next generation sequencing (NGS)-based method in the bone marrow.

  3. Number of participants with sustained MRD[-]CR [ Time Frame: 26 months ]
    Sustained MRD[-]CR response at a sensitivity of 10^-5 using NGS-based method in the bone marrow defined as subjects that maintain MRD[-]CR 12 months or more after achieving MRD[-]CR status, disregarding when the first MRD[-]CR was reached.

  4. Number of participants with sustained MRD[-]CR [ Time Frame: 24 months ]
    Sustained MRD[-]CR response at a sensitivity of 10^-5 using NGS-based method in the bone marrow at 24 months ± 4 weeks from start of treatment and calculated only within the subjects who reached MRD[-]CR in the time window for primary endpoint assessment.

  5. Overall response rate (ORR) [ Time Frame: 60 months ]
    Estimate overall response defined as the best overall confirmed response of partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) by Independent Review Committee (IRC) per International Myeloma Working Group Uniform Response Criteria (IMWG-URC).

  6. Overall response rate at 12 month landmark [ Time Frame: 12 months ]
    Estimate a landmark overall response by 12 months, defined as the best overall confirmed response of partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) by 12 months from start of treatment.

  7. Duration of response [ Time Frame: From start of treatment until disease progression or death from any cause (approximately 5 years) ]
    Estimate duration of response, defined as time from first date of partial response (PR) or better to date of disease progression or death due to any cause.

  8. Time to response [ Time Frame: From start of treatment until disease progression or death from any cause (approximately 5 years) ]
    Estimate time to response, defined as time from start of treatment to first date of partial response (PR) or better.

  9. Progression-free survival (PFS) [ Time Frame: From start of treatment until disease progression or death from any cause (approximately 5 years) ]
    Estimate Progression-free survival (PFS) defined as time from start of treatment until progression or death from any cause.

  10. Overall survival (OS) [ Time Frame: From start of treatment until disease progression or death from any cause (approximately 5 years) ]
    Estomate Overall Survival (OS), defined as time from start of treatment until death from any cause.

  11. Best overall confirmed response of complete response (CR) or better [ Time Frame: Up to 60 months ]
    Estimate complete response (CR) rate of carfilzomib, pomalidomide and dexamethasone (KPd) cohort.



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 to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Subject has provided informed consent prior to initiation of any study specific activities or procedures.
  • Male or female subjects age ≥ 18 years
  • First or second relapse of multiple myeloma by International Myeloma Working Group (IMWG) criteria (subjects refractory to the most recent line of therapy, excluding carfilzomib, are eligible)
  • Prior treatment with lenalidomide
  • Prior treatment includes completion of at least 2 consecutive cycles of daratumumab
  • Measurable disease with at least 1 of the following assessed within 28 days prior to enrollment:

    • IgG multiple myeloma: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL
    • IgA, IgD, IgE multiple myeloma: serum M-protein level ≥ 0.5 g/dL
    • urine M-protein ≥ 200 mg per 24 hours
    • in subjects without measurable serum or urine M-protein, serum-free light chain (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio
  • Must have at least a partial response (PR) to at least 1 line of prior therapy
  • Prior therapy with PI is allowed. Subjects receiving prior carfilzomib therapy must have achieved at least a PR, was not removed due to toxicity, did not relapse within 60 days from discontinuation of carfilzomib, and must have at least a 6 month carfilzomib treatment-free interval from their last dose of carfilzomib
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2

Exclusion Criteria

  • Primary refractory multiple myeloma
  • Waldenström macroglobulinemia
  • Multiple myeloma of IgM subtype
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Plasma cell leukemia ( greater than 2.0 × 109/L circulating plasma cells by differential). If automated differential shows ≥ 20% of other cells, obtain manual differential to identify other cells.
  • Primary amyloidosis (patients with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met)
  • Previous diagnosis of amyloidosis associated with myeloma
  • Myelodysplastic syndrome
  • Toxicity requiring discontinuation of lenalidomide therapy
  • Prior treatment with pomalidomide

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): NCT04191616


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

Locations
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Greece
Research Site
Alexandroupoli, Greece, 68100
Research Site
Athens, Greece, 10676
Research Site
Athens, Greece, 11528
Research Site
Thessaloniki, Greece, 54007
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: NCT04191616    
Other Study ID Numbers: 20180117
2019-001169-34 ( EudraCT Number )
First Posted: December 10, 2019    Key Record Dates
Last Update Posted: July 22, 2020
Last Verified: July 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: http://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:
Multiple Myeloma
RRMM
Open-label
First Relapse Multiple Myeloma
Second Relapse Multiple Myeloma
Refractory to Lenalidomide
Triplicate Treatment Regimen
dexamethasone
Carfilzomib
Pomalidomide
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
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