Treatment for relapsed or refractory light chain amyloidosis using venetoclax and dexamethasone
An Open-label Phase I/II Trial of Venetoclax-Dexamethasone in Relapsed and/or Refractory t(11;14) Systemic Light-Chain Amyloidosis
This study is testing a combination of venetoclax and dexamethasone to see if it helps people with relapsed or hard-to-treat light chain amyloidosis feel better compared to standard treatments.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 53 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Columbia University Academic / other |
| Drugs / interventions | daratumumab |
| Locations | 4 sites (Boston, Massachusetts and 3 other locations) |
| Trial ID | NCT05451771 on ClinicalTrials.gov |
What this trial studies
This clinical trial evaluates the safety and effectiveness of a combination therapy using venetoclax and dexamethasone for patients with relapsed or refractory t(11;14) systemic light chain amyloidosis. The study consists of two phases: a phase 1 dose escalation to determine the maximum tolerated dose of venetoclax, followed by a phase 2 randomized comparison of this optimal dose against standard treatment options. Participants will be monitored for treatment response and safety throughout the trial.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of t(11;14) positive relapsed or refractory light chain amyloidosis who have received prior therapies.
Not a fit: Patients with known hypersensitivity to the study drugs or those with other malignancies that could interfere with the study outcomes may not benefit from this trial.
Why it matters
Potential benefit: If successful, this treatment could provide a new effective option for patients with a challenging form of amyloidosis.
How similar studies have performed: Other studies have shown promise with similar combination therapies in treating amyloidosis, suggesting potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age ≥ 18 years at time of signing Informed Consent Form * Ability to comply with the study protocol, in the investigator's judgment * Confirmed diagnosis of systemic AL amyloidosis by mass spectrometry or immunohistochemistry (IHC) on a tissue biopsy * Has received ≥1 prior lines of therapy, including an anti-cluster of differentiation 38 (CD 38) monoclonal antibody * Participants with a history of autologous hematopoietic cell transplantation must have recovered from any transplant-related toxicities * Presence of t(11;14) on FISH at any time since diagnosis (Eligibility must confirmed by FISH testing at Columbia University Irving Medical Center (CUIMC) * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Exclusion Criteria: * Known hypersensitivity to any of the study drugs * History of other malignancy that could affect compliance with the protocol or interpretation of results (Patients with a history of curatively treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, breast cancer, or Hodgkin's Lymphoma are generally eligible. Patients with a malignancy that has been treated, but not with curative intent, will be excluded, unless the malignancy has been in remission without treatment for ≥ 2 years prior to enrollment.) * Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal) * Patients on renal replacement therapy * Known GI disease or GI procedure that could interfere with oral absorption (including difficulty swallowing) * New York Heart Association (NYHA) Class III or IV heart failure * Mayo stage three-B (IIIB) with N-terminal pro-hormone B-type natriuretic peptide (NT-Pro BNP) \> 8500 pg/mL * Prior exposure to anti-apoptotic protein B-cell lymphoma 2 (BCL-2) inhibitors * Patients with human immunodeficiency virus (HIV) who are not on highly active antiretroviral therapy (HAART) or those with active hepatitis A, B, or C infection * Patients meeting criteria for symptomatic multiple myeloma by one of the following:(a) Lytic lesions on imaging (b) Plasmacytoma, (c) Hypercalcemia without any alternate etiology, or (c) Bone marrow plasma cell infiltrate of greater than 60%
Where this trial is running
Boston, Massachusetts and 3 other locations
- Boston Medical Center — Boston, Massachusetts, United States (Recruiting)
- Mayo Clinic Rochester — Rochester, Minnesota, United States (Recruiting)
- New York Presbyterian Hospital/Columbia University Irving Medical Center — New York, New York, United States (Recruiting)
- Froedtert Hospital & the Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)
Study contacts
- Principal investigator: Rajshekhar Chakraborty, MD — Columbia University
- Study coordinator: Research Nurse Navigator
- Email: cancerclinicaltrials@cumc.columbia.edu
- Phone: 212-342-5162
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.