Actively Recruiting
A Phase I Study Investigating the Safety & Efficacy of Danvatirsen as Monotherapy Followed by Combination With Venetoclax in Patients With Relapsed/Refractory MDS & AML
Led by Montefiore Medical Center · Updated on 2025-11-10
38
Participants Needed
2
Research Sites
143 weeks
Total Duration
On this page
Sponsors
M
Montefiore Medical Center
Lead Sponsor
M
M.D. Anderson Cancer Center
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and effectiveness of Danvatirsen alone and then combined with Venetoclax in patients with relapsed or refractory myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). This Phase 1 study focuses on patients with intermediate to very high risk MDS or AML who have not responded to frontline therapy, aiming to find a safe and biologically effective dose for future studies. The trial also explores how blocking STAT3, a protein involved in cancer cell survival, affects disease progression and treatment resistance. The study includes two parts: one where patients receive Danvatirsen alone and another where Danvatirsen is combined with Venetoclax. Danvatirsen is given as an infusion with increasing doses over 28-day cycles, while Venetoclax is taken orally with a gradual dose increase during the first cycle. Dose levels and safety are carefully monitored to find the maximum tolerated dose. Treatment continues in cycles of about four weeks, with dose adjustments allowed based on side effects. Participants will have regular assessments including bone marrow biopsies and blood tests to monitor response and safety. Evaluations occur between days 21 and 42 of treatment cycles and continue at defined intervals to determine if the therapy is working or if side effects require stopping treatment. After completing the study treatment, patients will be followed every three months for up to three years to track long-term response and survival. Safety monitoring includes frequent checks and follow-up visits if treatment is stopped due to adverse effects.
CONDITIONS
Brief Title
Danvatirsen Monotherapy Followed by Combination With Venetoclax in Relapsed/Refractory MDS & AML
Who Can Participate
Eligibility Criteria
You may qualify if you...
- At least 18 years old and able to provide informed consent
- Confirmed diagnosis of AML or MDS by WHO criteria
- Relapsed or refractory AML with no approved treatment options, or intermediate/high/very high risk MDS refractory or relapsed to at least 2 cycles of hypomethylating agent therapy
- At least 3 months since allogeneic stem cell transplant with no active graft versus host disease
- White blood cell count below 25,000 cells/uL (may use hydroxyurea to reduce)
- Bone marrow biopsy within 28 days before study entry with tissue collected for analysis
- ECOG Performance Status of 0 to 2
- Recovery to Grade 1 or baseline for prior treatment toxicities except hair loss
- Adequate liver and kidney function according to specified lab values
- Use of two forms of contraception if aged 18 to 50 years
You will not qualify if you...
- Diagnosis of acute promyelocytic leukemia
- Low or very low risk MDS after failure of first-line hypomethylating agents
- Active uncontrolled infection (controlled infections allowed)
- Active central nervous system leukemia without recent clearance
- Use of prohibited medications or concurrent cancer treatments within 14 days before trial
- Other malignancies requiring treatment within 6 months except certain skin or treated cancers
- Pregnant or breastfeeding females
- Current alcohol or drug abuse
- Significant heart disease within past 6 months
- Psychiatric conditions impairing consent
- Legal incapacity to consent
- Any condition making the patient unsuitable for trial or investigational treatment
- Previous exposure to Danvatirsen
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 2 years to complete dose escalation; individual cycles approximately 4 weeks
Participants receive Danvatirsen monotherapy in dose-escalation cohorts to evaluate safety and determine the maximum tolerated dose. Treatment cycles last approximately 4 weeks with loading doses followed by weekly infusions.
Weekly visits during each 4-week cycle
Duration - Up to 1.5 years to complete dose escalation; individual cycles approximately 4 weeks
Participants receive combination therapy with Danvatirsen and Venetoclax in dose-escalation cohorts to evaluate safety and determine the maximum tolerated dose. Venetoclax dose is escalated over the first 3 days each cycle. Treatment cycles last approximately 4 weeks.
Daily Venetoclax dosing with weekly Danvatirsen infusions during each 4-week cycle
Duration - Ongoing throughout treatment
Participants undergo response evaluations including bone marrow aspiration and biopsy between Day 21 and Day 42 of the first and subsequent treatment cycles to assess treatment effectiveness.
Multiple visits prior to cycles 3, 5, 7, and every 2 cycles thereafter
Duration - Up to 3 years
Participants are followed every 3 months for up to 3 years after treatment ends to monitor response, disease progression, and overall survival until subsequent anticancer therapy begins or disease progresses.
Quarterly visits every 3 months
Trial Site Locations
Total: 2 locations
1
Montefiore Medical Center
The Bronx, New York, United States, 10467
Actively Recruiting
2
M.D. Anderson Cancer Center, Department of Leukemia
Houston, Texas, United States, 77030
Actively Recruiting
Research Team
A
Aditi Shastri, MBBS
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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