53 Participants Needed

Venetoclax + Dexamethasone for AL Amyloidosis

Recruiting at 2 trial locations
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Overseen ByResearch Nurse Navigator
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug Venetoclax for AL Amyloidosis?

Research shows that Venetoclax, when used for relapsed or refractory AL Amyloidosis, achieved a high response rate of 88% in patients, with many experiencing significant improvements. Additionally, Venetoclax has shown effectiveness in treating other blood-related conditions, like chronic lymphocytic leukemia, with response rates around 80%.12345

What makes the drug Venetoclax + Dexamethasone unique for treating AL Amyloidosis?

Venetoclax is unique because it targets a specific protein called BCL-2, which helps cancer cells survive, making it different from other treatments that may not target this protein. Dexamethasone is often used to reduce inflammation and can help enhance the effects of Venetoclax, offering a novel combination approach for AL Amyloidosis.678910

What is the purpose of this trial?

The purpose of this study is assess safety, safest dose, and effectiveness of venetoclax in combination with dexamethasone in participants with t(11;14) positive relapsed (comes back) or refractory (did not get better) light chain amyloidosis.

Research Team

RC

Rajshekhar Chakraborty, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for adults over 18 with relapsed or refractory AL amyloidosis, a condition where abnormal proteins build up in organs. Participants must have had prior treatments including an anti-CD38 antibody and be able to follow the study plan. They can't join if they're on dialysis, have certain infections like HIV without effective treatment, severe heart failure, previous use of BCL-2 inhibitors, or other serious health issues.

Inclusion Criteria

I have been treated with an anti-CD38 drug before.
My tests show I have the t(11;14) genetic marker.
Ability to comply with the study protocol, in the investigator's judgment
See 3 more

Exclusion Criteria

I have HIV but am not on HAART, or I have active hepatitis A, B, or C.
My heart condition is at stage IIIB with high NT-Pro BNP levels.
I had cancer before, but it's either been treated successfully or has been in remission for over 2 years.
See 7 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

Dose escalation to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of venetoclax in combination with dexamethasone

Up to 6 cycles (approximately 6 months)

Phase 2: Randomized Treatment

Randomized open-label study comparing the MTD or RP2D of venetoclax in combination with dexamethasone versus investigator's choice

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 8 weeks for up to 1 year

Treatment Details

Interventions

  • Venetoclax
Trial Overview The trial tests the safety and effectiveness of venetoclax combined with dexamethasone in patients whose amyloidosis has returned or didn't respond to treatment. It aims to find the safest dose and see how well it works against this disease that affects organ function by protein accumulation.
Participant Groups
6Treatment groups
Experimental Treatment
Active Control
Group I: Phase 2: Venetoclax MTD with DexamethasoneExperimental Treatment1 Intervention
Venetoclax MTD (200 mg or 400 mg) with Dexamethasone (10 mg or 20 mg) as determined by the phase I results
Group II: Phase 1: Venetoclax 400mg + Dexamethasone 20 mgExperimental Treatment3 Interventions
Cohort 4: Venetoclax 400 mg tablet, once daily and Dexamethasone 20 mg tablet once weekly, for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)
Group III: Phase 1: Venetoclax 400mg + Dexamethasone 10 mgExperimental Treatment3 Interventions
Cohort 3: Venetoclax 400 mg tablet, once daily and Dexamethasone 10 mg tablet once weekly, for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)
Group IV: Phase 1: Venetoclax 400mgExperimental Treatment2 Interventions
Cohort 2: Venetoclax 400 mg tablet, once daily for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)
Group V: Phase 1: Venetoclax 200 mgExperimental Treatment2 Interventions
Cohort 1: Venetoclax 200 mg tablet, once daily for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)
Group VI: Phase 2: Control Arm (Investigator's Choice)Active Control5 Interventions
Participants will receive one of the following as determined by the investigator: Daratumumab, Pomalidomide, Bendamustine, or Ixazomib (+/- dexamethasone)

Venetoclax is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Venclexta for:
  • Chronic lymphocytic leukemia (CLL)
  • Small lymphocytic lymphoma (SLL)
  • Acute myeloid leukemia (AML)
🇪🇺
Approved in European Union as Venclyxto for:
  • Chronic lymphocytic leukemia (CLL)
  • Small lymphocytic lymphoma (SLL)
  • Acute myeloid leukemia (AML)

Find a Clinic Near You

Who Is Running the Clinical Trial?

Rajshekhar Chakraborty, MD

Lead Sponsor

Trials
2
Recruited
140+

Genentech, Inc.

Industry Sponsor

Trials
1,578
Recruited
569,000+
Ashley Magargee profile image

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway profile image

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

A heart-transplanted patient with immunoglobulin light-chain amyloidosis (AL), who was resistant to multiple treatments, achieved a rapid complete response using the Bcl-2 inhibitor venetoclax as a single-agent therapy.
This case suggests that venetoclax may be a promising treatment option for AL, particularly in patients with the t(11;14) cytogenetic aberration, who typically have limited therapeutic options.
Rapid Complete Response to Single-Agent Bcl-2 Inhibitor Venetoclax in a Heart-Transplanted Patient with Triple Refractory Immunoglobulin Light-Chain Amyloidosis.Gran, C., Borg Bruchfeld, J., Ellin, F., et al.[2020]
In a phase I study involving 48 patients with relapsed or refractory multiple myeloma (RRMM), the combination of venetoclax with daratumumab and dexamethasone (VenDd) showed a remarkable overall response rate of 96%, indicating its strong efficacy, especially in patients with the t(11;14) translocation.
The combination of venetoclax with bortezomib, daratumumab, and dexamethasone (VenDVd) also demonstrated significant efficacy, with a 92% overall response rate, and an 18-month progression-free survival rate of 66.7%, suggesting that these combinations could provide durable responses in RRMM treatment.
Phase I Study of Venetoclax Plus Daratumumab and Dexamethasone, With or Without Bortezomib, in Patients With Relapsed or Refractory Multiple Myeloma With and Without t(11;14).Bahlis, NJ., Baz, R., Harrison, SJ., et al.[2022]
In a study of 22 relapsed/refractory multiple myeloma patients, low-dose venetoclax (≤250 mg/day) combined with bortezomib, daratumumab, and dexamethasone showed an impressive overall response rate of 80% in patients with the t(11;14) chromosomal marker, indicating its efficacy as a salvage therapy.
The low-dose regimen significantly reduced the incidence of serious adverse events, particularly infections, which are commonly associated with higher doses of venetoclax, suggesting a safer treatment option for this specific patient group.
Low dose venetoclax in combination with bortezomib, daratumumab, and dexamethasone for the treatment of relapsed/refractory multiple myeloma patients-a single-center retrospective study.Regidor, B., Goldwater, MS., Wang, J., et al.[2021]

References

Rapid Complete Response to Single-Agent Bcl-2 Inhibitor Venetoclax in a Heart-Transplanted Patient with Triple Refractory Immunoglobulin Light-Chain Amyloidosis. [2020]
Phase I Study of Venetoclax Plus Daratumumab and Dexamethasone, With or Without Bortezomib, in Patients With Relapsed or Refractory Multiple Myeloma With and Without t(11;14). [2022]
Low dose venetoclax in combination with bortezomib, daratumumab, and dexamethasone for the treatment of relapsed/refractory multiple myeloma patients-a single-center retrospective study. [2021]
Venetoclax in Relapse/Refractory AL Amyloidosis-A Multicenter International Retrospective Real-World Study. [2023]
Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]
Dexamethasone versus ondansetron in the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic surgery: a meta-analysis of randomized controlled trials. [2018]
Efficacy comparison of ramosetron with ondansetron on preventing nausea and vomiting in high-risk patients following spine surgery with a single bolus of dexamethasone as an adjunct. [2021]
The addition of dexamethasone to dolasetron or haloperidol for treatment of established postoperative nausea and vomiting. [2013]
Dexamethasone and postoperative analgesia in minimally invasive thoracic surgery: a retrospective cohort study. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Comparative study of dexamethasone and ondansetron for prophylaxis of postoperative nausea and vomiting in laparoscopic gynecologic surgery. [2022]
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