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Study to Determine Recommended Phase 2 Dose of Intravenous (IV) Eftozanermin Alfa in Combination With IV or Subcutaneous (SC) Bortezomib and Oral Dexamethasone Tablet and to Assess Change in Disease Symptoms in Adult Participants With Relapsed or Refractory Multiple Myeloma

NCT04570631

Description:

Multiple myeloma (MM) is a rare cancer caused by abnormal survival of plasma cells (blood cells). Most trial participants with MM relapse (cancer has come back) or become non- responsive to treatment and remission gets shorter after each line of treatment. This is a study to determine recommended Phase 2 dose and change in disease symptoms of eftozanermin alfa in combination with bortezomib and dexamethasone to assess how efficient the treatment is in adult participants with relapsed/refractory (R/R) MM. Eftozanermin alfa (ABBV-621) is an investigational drug being developed for the treatment of R/R Multiple Myeloma (MM). Study doctors put the participants in 1 of the 2 groups, called treatment arms. Each group receives a different treatment. Participants in one arm will receive different doses of eftozanermin alfa in combination with bortezomib and dexamethasone to determine phase 2 dose (RP2D). Participants in the other arm will receive eftozanermin alfa at RP2D in combination with bortezomib and dexamethasone. Around 40 adult participants with relapsed/refractory multiple myeloma will be enrolled at approximately 20 sites across the world. Participants will receive eftozanermin alfa as an infusion into the vein in combination with bortezomib as an infusion into the vein or an injection under the skin and oral dexamethasone tablets for 12 cycles. Each cycle is 21 days for cycles 1-8 and 35 days for cycles 9-12. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study to Determine Recommended Phase 2 Dose of Intravenous (IV) Eftozanermin Alfa in Combination With IV or Subcutaneous (SC) Bortezomib and Oral Dexamethasone Tablet and to Assess Change in Disease Symptoms in Adult Participants With Relapsed or Refractory Multiple Myeloma
  • Official Title: A Phase 1b, Open-Label Study of Eftozanermin Alfa (ABBV-621) in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: M20-258
  • SECONDARY ID: 2020-001983-26
  • NCT ID: NCT04570631

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
Eftozanermin alfaABBV-621Dose Expansion
BortezomibDose Expansion
DexamethasoneDose Expansion

Purpose

Multiple myeloma (MM) is a rare cancer caused by abnormal survival of plasma cells (blood cells). Most trial participants with MM relapse (cancer has come back) or become non- responsive to treatment and remission gets shorter after each line of treatment. This is a study to determine recommended Phase 2 dose and change in disease symptoms of eftozanermin alfa in combination with bortezomib and dexamethasone to assess how efficient the treatment is in adult participants with relapsed/refractory (R/R) MM. Eftozanermin alfa (ABBV-621) is an investigational drug being developed for the treatment of R/R Multiple Myeloma (MM). Study doctors put the participants in 1 of the 2 groups, called treatment arms. Each group receives a different treatment. Participants in one arm will receive different doses of eftozanermin alfa in combination with bortezomib and dexamethasone to determine phase 2 dose (RP2D). Participants in the other arm will receive eftozanermin alfa at RP2D in combination with bortezomib and dexamethasone. Around 40 adult participants with relapsed/refractory multiple myeloma will be enrolled at approximately 20 sites across the world. Participants will receive eftozanermin alfa as an infusion into the vein in combination with bortezomib as an infusion into the vein or an injection under the skin and oral dexamethasone tablets for 12 cycles. Each cycle is 21 days for cycles 1-8 and 35 days for cycles 9-12. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects.

Trial Arms

NameTypeDescriptionInterventions
Safety Lead-inExperimentalParticipants will receive escalating doses of eftozanermin alfa in combination with bortezomib and dexamethasone to determine recommended phase 2 dose (RP2D).
  • Eftozanermin alfa
  • Bortezomib
  • Dexamethasone
Dose ExpansionExperimentalParticipants will receive eftozanermin alfa at RP2D determined in Safety Lead-in part in combination with bortezomib and dexamethasone.
  • Eftozanermin alfa
  • Bortezomib
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Documented diagnosis of multiple myeloma (MM) based on standard International Myeloma
             Working Group (IMWG) criteria.

          -  Has measurable disease at screening, defined by at least 1 of the following:

               -  Serum M-protein >= 1.0 g/dL (>= 10 g/L); OR

               -  Urine M-protein >= 200 mg/24 hours; OR

               -  Serum free light chain (sFLC) >= 10 mg/dL (100 mg/L), provided serum FLC ratio is
                  abnormal.

          -  Relapsed or refractory MM after receiving at least 3, but no more than 6 prior lines
             of therapy, including an immunomodulatory agent (IMiD), proteasome inhibitor (PI), and
             an anti-CD38 antibody, and has documented disease progression that occurred during or
             after the most recent therapy.

          -  Has adequate hematologic, hepatic and renal function as defined in the protocol.

          -  Eastern Cooperative Oncology Group (ECOG) 0 or 1.

          -  Life expectancy >= 12 weeks.

        Exclusion Criteria:

          -  Received bortezomib as part of the most recent prior therapy.

          -  Has primary refractory disease defined as disease that is non-responsive.

          -  Has not achieved a minimal response or better per IMWG criteria with any therapy.

          -  Has discontinued bortezomib due to toxicity.

          -  History of chronic liver disease or significant unresolved liver disease; currently
             active (within the last 6 months) hepatic impairment according to Child-Pugh
             Classification B or C.

          -  Peripheral neuropathy Grade >= 2 or Grade 1 with pain.

          -  Receipt of one of the following:

               -  Corticosteroids at a dose equivalent to > 4 mg daily of dexamethasone or a single
                  dose of > 40 mg of dexamethasone within 2 weeks prior to first dose.

               -  Monoclonal antibodies used for multiple myeloma treatment within 4 weeks prior to
                  first dose of study treatment.

               -  Any other systemic therapies used for multiple myeloma treatment within 5
                  half-lives or 2 weeks prior to first dose, whichever is longer (or 2 weeks if
                  half-life is unknown).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase 2 Dose (RP2D) of Eftozanermin Alfa in Combination With Bortezomib and Dexamethasone (Safety Lead-In Arm)
Time Frame:Up to approximately 3 weeks after the first dose of study drug
Safety Issue:
Description:RP2D of eftozanermin alfa in combination with bortezomib and dexamethasone will be determined.

Secondary Outcome Measures

Measure:Rate of VGPR or Better per IMWG Criteria
Time Frame:Up to approximately 44 weeks after the first dose of study drug
Safety Issue:
Description:Percentage of participants with a response of VGPR or better per IMWG criteria will be assessed.
Measure:Duration of Response (DOR) for ORR
Time Frame:Up to approximately 44 weeks after the first dose of study drug
Safety Issue:
Description:DOR for ORR is defined as the number of days from the date of first response (PR or better) to the date of first occurrence of progressive disease (PD) or death from any cause, whichever occurs first.
Measure:Duration of Response (DOR) for VGPR or Better
Time Frame:Up to approximately 44 weeks after the first dose of study drug
Safety Issue:
Description:DOR for VGPR or better rate is defined as the number of days from the date of first response (VGPR or better) to the date of first occurrence of PD or death from any cause, whichever occurs first.
Measure:Number of Participants With Dose-Limiting Toxicities (DLTs)
Time Frame:Up to approximately 3 weeks after the first dose of study drug
Safety Issue:
Description:DLTs are any of the hematologic, nonhematologic toxicities, adverse events (AEs) occurring following administration of study drug as described in the protocol and evaluated by the Investigator and the sponsor.
Measure:Number of Participants With Adverse Events (AEs)
Time Frame:Up to approximately 44 weeks after the first dose of study drug
Safety Issue:
Description:An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator will assess the relationship of each event to the use of study drug as being of reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above.
Measure:Change in Vital Sign Measurements
Time Frame:Up to approximately 44 weeks after the first dose of study drug
Safety Issue:
Description:Change from baseline in vital sign measurements such as systolic and diastolic blood pressure will be assessed.
Measure:Electrocardiogram (ECG)
Time Frame:Up to approximately 44 weeks after the first dose of study drug
Safety Issue:
Description:Participants with change from baseline in ECG variables will be assessed.
Measure:Number of Participants With Abnormal Clinical Laboratory Test Results
Time Frame:Up to approximately 44 weeks after the first dose of study drug
Safety Issue:
Description:Number of participants with abnormal clinical laboratory test results like hematology will be assessed.
Measure:Trough Concentration (Ctrough) of Eftozanermin Alfa
Time Frame:Up to Day 106
Safety Issue:
Description:Serum concentration prior to administration of study drug.
Measure:Maximum Serum Concentration (Cmax) of Eftozanermin Alfa
Time Frame:Up to Day 8
Safety Issue:
Description:Serum concentration at 15 min after end of infusion.
Measure:Antidrug Antibody (ADA)/Neutralizing Antibody (Nab) Assay
Time Frame:Up to approximately 44 weeks after the first dose of study drug
Safety Issue:
Description:Serum sample assay for ADA/Nab (Nabs will be analyzed only upon request).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Multiple Myeloma (MM)
  • Relapsed/Refractory Multiple Myeloma
  • Eftozanermin Alfa
  • ABBV-621
  • Bortezomib
  • Dexamethasone

Last Updated

September 29, 2020