Danvatirsen Monotherapy Followed by Combination With Venetoclax in Relapsed/Refractory MDS & AML
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorMontefiore Medical Center
About this trial
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
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Subjects must be at least 18 years of age at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF; and be able to meet all study requirements
Morphologically confirmed diagnosis of AML or MDS in accordance with World Health Organization (WHO) diagnostic criteria
Subjects with relapsed/refractory AML who are refractory or relapsed to all conventional therapy and do not have any FDA approved or standard therapeutic options & subjects with intermediated/high/very high IPSS-R MDS who are refractory or relapsed to at least 2 cycles of hypomethylating agent based therapy (azacitidine / decitabine based) OR patients with rapid progression of disease regardless of number of cycles of therapy
At least 3 months from Allogenic stem cell transplantation and no clinical sign of active graft vs host disease (GVHD)
Disqualifiers
Acute Promyelocytic Leukemia
Low or very low risk MDS by IPSS-R after failure/progression of first line therapy with hypomethylating agents
Active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible. Use of prophylactic anti-microbials per institutional standards is allowed
Active documented central nervous system (CNS) leukemia. Patients with a known history of CNS leukemia will be eligible if they have at least two most recent consecutive LPs showing clearance of CNS disease and no active/progressive symptoms thought to be related to the CNS disease
Trial design
Design model
Parallel
Treatments tested in this trial
Danvatirsen
DrugDanvatirsen (AZD9150) is a selective, high-affinity, antisense oligonucleotide inhibitor of signal transducer and activator of transcription 3 (or STAT3).
Danvatirsen + Venetoclax
Combination productDanvatirsen (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.
Treatment groups
38 Participants
are divided into 2 treatment groupsGroup A: Danvatirsen MonotherapyExperimental treatment 1 intervention
Group B: Danvatirsen + Venetoclax Combination TherapyExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Response to Therapy as determined by Overall Response Rate
Overall Response Rate (ORR) will be used to assess clinical activity in AML and MDS participants. ORR will be measured as the percentage of participants demonstrating an objective overall response based upon a composite of remission related measures for AML and MDS participants as defined below. For AML participants, ORR will be defined as any confirmed Complete Remission (CR) + Complete Remission with Incomplete hematologic recovery (CRi) + Partial Remission (PR). or, AML = CR + CRi + PR For MDS participants, ORR will be defined as any confirmed Complete Remission (CR) + Complete Remission with Partial Hematologic Recovery (CRh) + Hematologic Response (HR). or, MDS = CR + CRh + HR Higher percentage is indicative of increased clinical activity of the danvatirsen monotherapy and danvatirsen + venetoclax combination therapies.
Time frame
From 21 days after initiation of study treatment to within 14 days following treatment discontinuation; up to 14 weeks totalSecondary outcomes
1
Duration of Response
Duration of response will be measured by the number of days from the date of initial response (CRi or better) to the date of first documented disease progression/relapse or death, whichever occurs first. In the event that neither disease progression/relapse or death is documented prior to study termination, analysis cutoff, or the start of confounding anticancer therapy, this endpoint will be censored at the date of last tumor assessment date. An increased duration of response is indicative of how long a patient will respond to treatment without tumor growth or metastasis
Time frame
Up to 3 years after discontinuation of study treatment; up to 3.5 years total2
Event-free survival
Event-free survival (EFS) will be measured as the number of days from the date of treatment initiation to the date of documented treatment failure, relapse from complete remission, or death from any cause, whichever occurs first. In the event that none of the above are documented prior to study termination, analysis cutoff, or the start of confounding anticancer therapy, this endpoint will be censored at the date of last tumor assessment date
Time frame
Up to 3 years after discontinuation of study treatment; up to 3.5 years total3
Overall Survival
Overall Survival (OS) will be measured as the number of days from the date of treatment initiation until the date of death
Time frame
Up to 3 years after discontinuation of study treatment; up to 3.5 years total4
30 Day All-cause mortality
Number of participant deaths by all causes
Time frame
30 days after initiation of study treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Montefiore Medical Center
Lead sponsor
M.D. Anderson Cancer Center
Collaborator
Flamingo Therapeutics NV
Collaborator
Source ClinicalTrials.gov