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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

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ClinicalTrials.gov Identifier: NCT04570631
Recruitment Status : Recruiting
First Posted : September 30, 2020
Last Update Posted : October 5, 2021
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Eftozanermin alfa Drug: Bortezomib Drug: Dexamethasone Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 5, 2020
Estimated Primary Completion Date : January 31, 2023
Estimated Study Completion Date : January 31, 2023


Arm Intervention/treatment
Experimental: Safety Lead-in
Participants will receive escalating doses of eftozanermin alfa in combination with bortezomib and dexamethasone to determine recommended phase 2 dose (RP2D).
Drug: Eftozanermin alfa
Intravenous (IV) infusion
Other Name: ABBV-621

Drug: Bortezomib
Intravenous (IV) or Subcutaneous (SC) injection

Drug: Dexamethasone
Oral Tablet

Experimental: Dose Expansion
Participants will receive eftozanermin alfa at RP2D determined in Safety Lead-in part in combination with bortezomib and dexamethasone.
Drug: Eftozanermin alfa
Intravenous (IV) infusion
Other Name: ABBV-621

Drug: Bortezomib
Intravenous (IV) or Subcutaneous (SC) injection

Drug: Dexamethasone
Oral Tablet




Primary Outcome Measures :
  1. 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 ]
    RP2D of eftozanermin alfa in combination with bortezomib and dexamethasone will be determined.

  2. Objective Response Rate (ORR) (Dose Expansion Arm) [ Time Frame: Up to approximately 44 weeks after the first dose of study drug ]
    ORR is defined as percentage of participants with a response of partial response (PR) or better per IMWG criteria.


Secondary Outcome Measures :
  1. Rate of VGPR or Better per IMWG Criteria [ Time Frame: Up to approximately 44 weeks after the first dose of study drug ]
    Percentage of participants with a response of VGPR or better per IMWG criteria will be assessed.

  2. Duration of Response (DOR) for ORR [ Time Frame: Up to approximately 44 weeks after the first dose of study drug ]
    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.

  3. Duration of Response (DOR) for VGPR or Better [ Time Frame: Up to approximately 44 weeks after the first dose of study drug ]
    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.

  4. Number of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: Up to approximately 3 weeks after the first dose of study drug ]
    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.

  5. Number of Participants With Adverse Events (AEs) [ Time Frame: Up to approximately 44 weeks after the first dose of study drug ]
    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.

  6. Change in Vital Sign Measurements [ Time Frame: Up to approximately 44 weeks after the first dose of study drug ]
    Change from baseline in vital sign measurements such as systolic and diastolic blood pressure will be assessed.

  7. Electrocardiogram (ECG) [ Time Frame: Up to approximately 44 weeks after the first dose of study drug ]
    Participants with change from baseline in ECG variables will be assessed.

  8. Number of Participants With Abnormal Clinical Laboratory Test Results [ Time Frame: Up to approximately 44 weeks after the first dose of study drug ]
    Number of participants with abnormal clinical laboratory test results like hematology will be assessed.

  9. Trough Concentration (Ctrough) of Eftozanermin Alfa [ Time Frame: Up to Day 106 ]
    Serum concentration prior to administration of study drug.

  10. Maximum Serum Concentration (Cmax) of Eftozanermin Alfa [ Time Frame: Up to Day 8 ]
    Serum concentration at 15 min after end of infusion.

  11. Antidrug Antibody (ADA)/Neutralizing Antibody (Nab) Assay [ Time Frame: Up to approximately 44 weeks after the first dose of study drug ]
    Serum sample assay for ADA/Nab (Nabs will be analyzed only upon request).



Information from the National Library of Medicine

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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:

  • 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).

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): NCT04570631


Contacts
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Contact: ABBVIE CALL CENTER 844-663-3742 abbvieclinicaltrials@abbvie.com

Locations
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Sponsors and Collaborators
AbbVie
Investigators
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Study Director: ABBVIE INC. AbbVie
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT04570631    
Other Study ID Numbers: M20-258
2020-001983-26 ( EudraCT Number )
First Posted: September 30, 2020    Key Record Dates
Last Update Posted: October 5, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by AbbVie:
Multiple Myeloma (MM)
Relapsed/Refractory Multiple Myeloma
Eftozanermin Alfa
ABBV-621
Bortezomib
Dexamethasone
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
Bortezomib
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