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A Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT03567616
Recruitment Status : Suspended (Safety)
First Posted : June 25, 2018
Last Update Posted : March 21, 2019
Sponsor:
Collaborator:
Celgene
Information provided by (Responsible Party):
AbbVie

Brief Summary:
This study is designed to evaluate the safety and preliminary efficacy of venetoclax combined with pomalidomide and dexamethasone in subjects with relapsed or refractory (R/R) multiple myeloma (MM) who have received at least 1 prior line of therapy. The study will consist of 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion). For Part 2 the subjects will be divided into 2 cohorts, subjects positive for t(11;14) translocation and subjects negative for t(11;14) translocation.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Venetoclax Drug: Pomalidomide Drug: Dexamethasone Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Multicenter, Dose-Escalation and Expansion Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : November 9, 2018
Estimated Primary Completion Date : August 20, 2020
Estimated Study Completion Date : January 22, 2021


Arm Intervention/treatment
Experimental: Dose-Escalation Phase
Dose-Escalation Phase subjects will administer venetoclax (various doses) + pomalidomide + dexamethasone.
Drug: Venetoclax
tablet; oral
Other Names:
  • ABT-199
  • GDC-0199

Drug: Pomalidomide
capsule; oral
Other Name: Pomalyst

Drug: Dexamethasone
administered orally

Experimental: Expansion Phase: Arm A t(11;14) Positive
Expansion Phase Arm A in subjects positive for t(11;14) translocation will administer venetoclax + pomalidomide + dexamethasone .
Drug: Venetoclax
tablet; oral
Other Names:
  • ABT-199
  • GDC-0199

Drug: Pomalidomide
capsule; oral
Other Name: Pomalyst

Drug: Dexamethasone
administered orally

Experimental: Expansion Phase: Arm B t(11;14) Negative
Expansion Phase Arm B in subjects negative for t(11;14) translocation will administer venetoclax + pomalidomide + dexamethasone.
Drug: Venetoclax
tablet; oral
Other Names:
  • ABT-199
  • GDC-0199

Drug: Pomalidomide
capsule; oral
Other Name: Pomalyst

Drug: Dexamethasone
administered orally




Primary Outcome Measures :
  1. Number of Participants With Adverse Events [ Time Frame: From first dose of study drug until 30 days following last 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 assessed the relationship of each event to the use of study drug as either 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. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Up to approximately 12 months ]
    ORR is defined as defined as the proportion of subjects experiencing a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).

  2. Progression-Free Survival (PFS) [ Time Frame: Up to approximately 18 months ]
    PFS is defined as the number of days from the date of first dose of any study drug to the date of disease progression or death, whichever occurs first. All disease progression will be included regardless whether the event occurred during or after the participant was taking any study drug.

  3. Duration of Response (DOR) [ Time Frame: Up to approximately 24 months ]
    DOR defined as the number of days from the date of that subject's first documented response (PR or better) to the date of first documented disease progression (PD) or death due to multiple myeloma, whichever occurs first.

  4. Time-to-progression (TTP) [ Time Frame: Up to approximately 24 months ]
    TPP is defined aas the number of days from the date of first dose to the date of first documented PD or death due to MM, whichever occurs first.

  5. Cmax of Venetoclax [ Time Frame: Up to approximately 7 months ]
    Cmax is defined as maximum concentration observed following venetoclax administration.

  6. Tmax of Venetoclax [ Time Frame: Up to approximately 7 months ]
    Tmax is defined as time to reach the maximum observed serum concentration (Cmax) for venetoclax.

  7. AUC0-24 of Venetoclax [ Time Frame: Up to approximately 7 months ]
    AUC0-24 is defined as the area under the plasma concentration versus time curve (AUC) from time 0 to 24 hours postdose (AUC0-24).

  8. Cmax of pomalidomide [ Time Frame: Up to 15 days after initial study drug ]
    Cmax is defined as maximum concentration observed following pomalidomide administration.

  9. Tmax of Pomalidomide [ Time Frame: Up to 15 days after initial study drug ]
    Tmax is defined as time to reach the maximum observed serum concentration (Cmax) for for pomalidomide.

  10. AUC0-24 of Pomalidomide [ Time Frame: Up to 15 days after initial study drug ]
    AUC0-24 is defined as the area under the plasma concentration versus time curve (AUC) from time 0 to 24 hours postdose (AUC0-24).



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:

  • Relapsed or refractory (R/R) multiple myeloma (MM) with documented evidence of progression during or after the subject's last treatment regimen.
  • Measurable disease as described in the protocol.
  • Received at least 1 prior line of therapy, as described in the protocol.
  • Must meet prior antimyeloma treatment parameters, as described in the protocol, and includes:
  • Received at least 2 consecutive cycles of lenalidomide or a lenalidomide containing regimen
  • Refractory to lenalidomide
  • Exposed to a proteasome inhibitor (PI) alone or in combination with another agent.
  • Had a response of partial response (PR) or better to prior therapy based on the investigator's determination of response as defined by International Myeloma Working Group (IMWG) criteria.
  • Has t(11;14) status as described in the protocol and meets the following criteria:
  • For Part 1: MM subjects independent of cytogenetic profile.
  • For Part 2, Arm A: subject must be t(11;14) positive.
  • For Part 2, Arm B: subject must be t(11;14) negative.
  • An Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Adequate kidney, liver and hematologic laboratory values.

Exclusion Criteria:

  • Previous treatment with venetoclax or other BCL-2 inhibitors, or previous treatment with pomalidomide
  • Known sensitivity to any IMiDs
  • Allogenic or syngeneic stem cell transplant within 6 months before the first dose of study drug or active ongoing graft versus host disease
  • Autologous stem cell transplant within 12 weeks before the first dose of study drug
  • Known meningeal involvement of MM

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): NCT03567616


Locations
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United States, Georgia
John B. Amos Cancer Center - C /ID# 202055
Columbus, Georgia, United States, 31904
United States, Kansas
University of Kansas Cancer Center /ID# 201292
Fairway, Kansas, United States, 66205-2528
United States, Massachusetts
Dana-Farber Cancer Institute /ID# 201297
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University-School of Medicine /ID# 201287
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Duke University Hospital /ID# 200805
Durham, North Carolina, United States, 27710
United States, Ohio
Ohio State Cancer Center /ID# 202443
Columbus, Ohio, United States, 43210
United States, Oregon
Oregon Health and Science University /ID# 205582
Portland, Oregon, United States, 97239-3098
United States, Wisconsin
Aurora Health Care, Aurora Cancer Center /ID# 201153
Wauwatosa, Wisconsin, United States, 53226-3436
Spain
Hospital Clinic de Barcelona /ID# 200957
Barcelona, Spain, 08028
Hospital Vall d'Hebron /ID# 200967
Barcelona, Spain, 08035-999999
Hospital Univ Germans Trias I /ID# 200959
Barcelona, Spain, 08916
Hospital Universitario La Paz /ID# 200969
Madrid, Spain, 28046
Hospital Clinico Univ de Salamanca /ID# 200958
Salamanca, Spain, 37007
United Kingdom
Leicester Royal Infirmary /ID# 202238
Leicester, England, United Kingdom, LE1 5WW
Univ Hospitals Birmingham NHS Foundation trust /ID# 203188
Birmingham, United Kingdom, B15 2TG
St. James University Hospital /ID# 202243
Leeds, United Kingdom, LS9 7TF
Norfolk and Norwich Univ Hosp /ID# 202240
Norwich, United Kingdom, NR4 7UY
Royal Marsden Hospital, The Ro /ID# 202242
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
AbbVie
Celgene
Investigators
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Study Director: AbbVie Inc. AbbVie

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03567616     History of Changes
Other Study ID Numbers: M16-085
First Posted: June 25, 2018    Key Record Dates
Last Update Posted: March 21, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

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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.: No

Keywords provided by AbbVie:
Cancer
Multiple Myeloma (MM)
Relapsed or Refractory (R/R)
venetoclax
pomalidomide
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
Dexamethasone acetate
Venetoclax
Pomalidomide
Thalidomide
BB 1101
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