A Study Evaluating Venetoclax (ABT-199) in Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Standard Therapy

What's the purpose of this trial?

This is a Phase 3, multicenter, randomized, double blind, placebo-controlled study evaluating the efficacy and safety of venetoclax plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma who are considered sensitive or naïve to proteasome inhibitors and received 1 to 3 prior lines of therapy for multiple myeloma.

This trial has suspended patient recruitment.


What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 2
  • Participant has documented relapsed or progressive multiple myeloma on or after any regimen or who are refractory to the most recent line of therapy. Relapsed myeloma is defined as previously treated myeloma that progresses and requires initiation of salvage therapy, but does not meet the criteria for refractory myeloma. Refractory myeloma is defined as disease that is non responsive (failure to achieve minimal response or development of progressive disease [PD]) while on primary or salvage therapy, or progresses within 60 days of last therapy.
  • Participant must have received prior treatment with at least one, but no more than three, prior lines of therapy for multiple myeloma. A line of therapy consists of greater than or equal to 1 complete cycle of a single agent, a regimen consisting of combination of several drugs, or a planned sequential therapy of various regimens.
  • Prior treatment with bortezomib or other proteasome inhibitor is allowed, provided ALL of the following criteria are met: Disease is NOT refractory to any proteasome inhibitor, defined as no disease progression (i.e., PD, per IMWG or European Society for Blood and Marrow Transplantation [EBMT] criteria) while receiving proteasome inhibitor therapy or within 60 days after the last dose, AND best response achieved with any proteasome inhibitor therapy (alone or in combination) was at least a PR, AND participant did not discontinue any proteasome inhibitor due to intolerance or greater than or equal to Grade 3 related toxicity.
  • Participant has measurable disease at Screening, defined as at least one of the following: Serum M-protein greater than or equal to 0.5 g/dL, OR Urine M-protein greater than or equal to 200 mg in 24-hours, OR serum immunoglobulin free light chain (FLC) greater than or equal to 10 mg/dL provided serum FLC ratio is abnormal.

Exclusion Criteria:

  • Participant is refractory to any proteasome inhibitor, defined as progression on or within 60 days of the last dose of a proteasome inhibitor-containing regimen.
  • Participant has had prior treatment with proteasome inhibitor within 60 days prior to first dose of study drug.
  • Participant has any of the following conditions:
    • Non-secretory or oligo-secretory multiple myeloma, active plasma cell leukemia i.e., either 20% of peripheral white blood cells or greater than 2.0 X 10^9/liter (L) circulating plasma cells by standard differential, waldenstrom's macroglobulinemia, amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), known Human Immunodeficiency Viral (HIV) infection, active hepatitis B or C infection based on blood screen tests, significant cardiovascular disease, including uncontrolled angina, severe or uncontrolled arrhythmia, recent myocardial infarction within 6 months of randomization, or congestive heart failure New York Heart Association (NYHA) Class greater than or equal to 3, Major surgery within 4 weeks prior to randomization, acute infections requiring parenteral therapy (antibiotic, antifungal, or antiviral) within 14 days prior to randomization, peripheral neuropathy greater than or equal to Grade 3 or greater than or equal to Grade 2 with pain within 2 weeks prior to randomization, uncontrolled diabetes or uncontrolled hypertension within 14 days prior to randomization, any other medical condition that, in the opinion of the Investigator, would adversely affect the participant's participation in the study
  • Participant has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions: Adequately treated in situ carcinoma of the cervix uteri or the breast, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, prostate cancer Gleason grade 6 or lower AND with stable Prostate Specific Antigen (PSA) levels off treatment, previous malignancy with no evidence of disease confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study
  • If participant had prior allogeneic stem cell transplant (SCT), participant has evidence of ongoing graft-versus-host disease (GvHD).

Additional Trial Information

Phase 3

Enrollment: 291 patients (estimated)

View More

Published Results

Final Overall Survival Results from BELLINI, a Phase 3 Study of Venetoclax or Placebo in Combination with Bortezomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma

December 11, 2021

Results: Of 291 randomized pts (194 to Ven and 97 to Placebo), 33 pts were receiving ongoing treatment (28 with Ven and 5 with Placebo) as of the final OS analysis data cutoff (March 15, 2021). At a median follow-up of 45.6 months, there were 78 (40%) deaths in the Ven arm versus 36 (37%) in the Placebo arm. Updated PFS and OS among all pts and those with t(11;14) or high BCL2 expression are shown in the Table. Among all pts, the median PFS per investigator was 23.4 months in the Ven arm versus 11.4 months in the Placebo arm (HR, 0.58 [95% CI, 0.43–0.78]). In pts with t(11;14), the median PFS was 36.8 months in the Ven arm versus 9.3 months in the Placebo arm (HR, 0.12 [95% CI, 0.03–0.44]). In pts with high BCL2, the median PFS was 30.1 months in the Ven arm versus 9.9 months in the Placebo arm (HR, 0.37 [95% CI, 0.21–0.64]). Median OS was not reached in the Ven or Placebo arm among all pts (HR, 1.19 [95% CI, 0.80–1.77]), pts with t(11;14) (HR, 0.61 [95% CI, 0.16–2.32]), pts with high BCL2 (HR, 0.70 [95% CI, 0.32–1.51]), and pts with t(11;14) or high BCL2 (HR, 0.82 [95% CI, 0.40–1.70]).

The most common treatment-emergent adverse events (AEs) with Ven (versus Placebo) were diarrhea (60% versus 50%), nausea (38% versus 23%), and constipation (35% versus 31%). The most common Grade 3/4 AEs (Ven versus Placebo) were thrombocytopenia (16% versus 30%), neutropenia (23% versus 8%), pneumonia (19% versus 13%), anemia (16% versus 15%), and diarrhea (15% versus 11%). Serious AEs occurred in 57% of Ven- and 55% of Placebo-treated pts, with serious infections and infestations occurring in 35% and 29% of pts, respectively. Overall, 26% of pts in the Ven arm and 11% of pts in the Placebo arm experienced an AE leading to Ven or Placebo discontinuation. AEs led to 12 deaths in the Ven arm, with 9 of these deaths due to serious infection; an AE led to 1 death in the Placebo arm. A total of 16 (6%) treatment-emergent deaths occurred (14 [7%] with Ven and 2 [2%] with Placebo), with 3 of these deaths due to disease progression (2 [1%] with Ven and 1 [1%] with Placebo).

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

Colorado

University of Colorado Cancer Center Anschutz Cancer Pavilion

Aurora, CO

Temporarily Suspended

Rocky Mountain Cancer Centers (Aurora) Aurora

Aurora, CO

Temporarily Suspended

Illinois

Loyola University Medical Center Cardinal Bernardin Cancer Center

Maywood, IL

Temporarily Suspended

Oncology Specialists S.C.

Park Ridge, IL

Temporarily Suspended

Minnesota

Mayo Clinic (Rochester)

Rochester, MN

Temporarily Suspended

New York

Northern Westchester Hospital

Mt. Kisco, NY

Temporarily Suspended

North Carolina

Duke Cancer Center Duke University Medical Center

Durham, NC

Temporarily Suspended

Ohio

Gabrail Cancer Center Research

Canton, OH

Temporarily Suspended
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