Danvatirsen Monotherapy Followed by Combination With Venetoclax in Relapsed/Refractory MDS & AML

Part of paid clinical trials in The Bronx, New York.

Sponsor
Montefiore Medical Center
Study ID
NCT05986240
Phase
PHASE1
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Accepted

Interventions

  • Danvatirsen — DRUG
    Danvatirsen (AZD9150) is a selective, high-affinity, antisense oligonucleotide inhibitor of signal transducer and activator of transcription 3 (or STAT3).
  • Danvatirsen + Venetoclax — COMBINATION_PRODUCT
    Danvatirsen (AZD9150) is a selective, high-affinity, antisense oligonucleotide inhibitor of signal transducer and activator of transcription 3 (or STAT3). Venetoclax: Commercially available. Venetoclax is a potent, selective small molecule inhibitor of BCL-2, an anti-apoptotic protein found on some types of cancer cells.

Study Details

This is a Phase 1 study investigating the safety and efficacy of Danvatirsen as a monotherapy followed by combination with Venetoclax in patients with relapsed/refractory myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Funding Source: FDA OOPD

Key Dates

Start date
May 8, 2024
Status verified
Nov 2025
Primary completion
Jun 30, 2027
Completion
Mar 31, 2030

Study Design

Enrollment
38 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Danvatirsen Monotherapy
    Patients will be enrolled in cohorts of 3 for the Danvatirsen dose escalation substudy. Based on the DLT of the first cohort of participants, subsequent cohorts will either be administered doses at the next higher dose level, de-escalated to the next lower dose level, or remain the same. Dose escalation discontinuations and MTD will be determined as described in the 'Detailed Study Description.' The total duration of 1 cycle is approximately 4 weeks (28 days). Proposed dose levels and treatment schedule are as follows: Dose Level 1 (DL1): Danvatirsen Day 1 - Day 28 (1mg/kg loading dose on Cycle 1/Day 1 (C1D1), Cycle 1/Day 3 (C1D3); and Cycle 1/Day 5 (C1D5) followed by weekly 1mg/kg infusion for 3 weeks) Dose Level 2 (DL2): Danvatirsen Day 1 - Day 28 (2mg/kg loading dose on C1D1, C1D3, and C1D5 followed by weekly 2mg/kg infusion for 3 weeks) Dose Level 3 (DL3): Danvatirsen Day 1 - Day 28 (3mg/kg loading dose on C1D1, C1D3, and C1D5 followed by weekly 3mg/kg infusion for 3 weeks)
  • Experimental: Danvatirsen + Venetoclax Combination Therapy
    Patients will be enrolled in cohorts of 3 for the Danvatirsen + Venetoclax dose escalation substudy. Dose escalation administration will be as described in the Danvatirsen monotherapy substudy arm and dose escalation discontinuations and MTD will be determined as described in the 'Detailed Study Description.' Up to 2 dose levels of Danvatirsen will be evaluated based on data from the Danvatirsen monotherapy arm. Dose 1 will be one level lower than the dose with expected target activity. Venetoclax: 400 mg (or equivalent) administered as fixed dose daily (except for specific dose modifications described in the protocol) orally for 28 days per cycle. To mitigate risk of tumor lysis syndrome, during Cycle 1 Venetoclax will be dose escalated daily to the goal dose of 400mg daily (100mg on Day 1, 200mg on Day 2 and 400mg on Day 3, and onwards, or adjusted dose ramp-up per Venetoclax label if on concomitant azoles). The three cycles are approximately 28 days each in duration.

Primary Outcome Measure

Response to Therapy as determined by Overall Response Rate [ Time Frame: From 21 days after initiation of study treatment to within 14 days following treatment discontinuation; up to 14 weeks total ]

Central Contacts

Locations (2)

FacilityCityStateZIPSite coordinators
Montefiore Medical CenterThe BronxNew York10467
Aditi Shastri, MBBS
[email protected]
718-920-4826
M.D. Anderson Cancer Center, Department of LeukemiaHoustonTexas77030
Naval Daver, MD
[email protected]
713-794-4392

Find similar trials in The Bronx, NY

By condition
Leukemia (other)
By specialty
OncologyBlood cancer
By research site
Montefiore Medical Center· The Bronx, NYM.D. Anderson Cancer Center, Department of Leukemia· Houston, TX

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