RECRUITING

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

Conditions

AML/MDS Acute Myeloid Leukemia Myelodysplastic Syndromes

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

A Phase I Study Investigating the Safety & Efficacy of Danvatirsen as Monotherapy Followed by Combination With Venetoclax in Patients With Relapsed/Refractory MDS & AML

Quick Facts

Study Start:2024-05-08

Study Completion:2028-07

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05986240

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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 4 cycles of hypomethylating agent based therapy (azacitidine / decitabine based) OR patients with rapid progression of disease regardless of number of cycles of therapy * WBC must be \<25,000 and may be reduced with hydroxyurea to reach this goal prior to study start * At least 3 months from Allogenic stem cell transportation and no clinical sign of active graft vs host disease (GVHD) * A post-consent bone marrow biopsy must be performed and tissue collected for correlative analysis for entrance to this trial. Correlative sample collection will not be optional on this study * Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 * Recovery to ≤ Grade 1 or baseline for any toxicities considered to be due to prior systemic treatments, excluding alopecia * Must have adequate hepatic and renal function as follows: * Serum creatinine clearance ≥ 60 mL/min/1.73 m2 either measured or calculated using standard Cockroft-Gault formula	* 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. * Concurrent treatment with a non-permitted concomitant medication (as noted in protocol appendix) * Concurrent anticancer treatment, major surgery, or the use of any investigational drug within 14 days before the start of trial treatment * Other malignancy currently being treated or likely to need treatment in next 6 months with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ, surgically removed malignancies or malignancies definitively treated with chemotherapy, XRT and/or surgery with no evidence of active malignancy or not anticipated to need treatment in next 6 months or malignancies on maintenance therapy (e.g. tamoxifen for breast cancer) will be allowed after discussion and approval by both MPIs * Pregnant or breastfeeding females * Known current alcohol or drug abuse * Clinically significant cardiovascular disease within the past 6 months (e.g. percutaneous intervention, coronary artery bypass graft, documented NYHA class III/IV cardiac heart failure, unstable angina or MI, poorly controlled atrial or ventricular arrhythmia) as determined by the investigator * Any psychiatric condition that would prohibit the understanding or rendering of informed consent * Legal incapacity or limited legal capacity to sign consent and/or participate in the trial * Any condition deemed by the investigator to make the patient a poor candidate for clinical trial and/or treatment with investigational agents. * Previous exposure to the investigational agent (danvatirsen) or to other STAT3 inhibitors

Inclusion Criteria

Exclusion Criteria

* 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 4 cycles of hypomethylating agent based therapy (azacitidine / decitabine based) OR patients with rapid progression of disease regardless of number of cycles of therapy
* WBC must be \<25,000 and may be reduced with hydroxyurea to reach this goal prior to study start
* At least 3 months from Allogenic stem cell transportation and no clinical sign of active graft vs host disease (GVHD)
* A post-consent bone marrow biopsy must be performed and tissue collected for correlative analysis for entrance to this trial. Correlative sample collection will not be optional on this study
* Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
* Recovery to ≤ Grade 1 or baseline for any toxicities considered to be due to prior systemic treatments, excluding alopecia
* Must have adequate hepatic and renal function as follows:
* Serum creatinine clearance ≥ 60 mL/min/1.73 m2 either measured or calculated using standard Cockroft-Gault formula

* 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.
* Concurrent treatment with a non-permitted concomitant medication (as noted in protocol appendix)
* Concurrent anticancer treatment, major surgery, or the use of any investigational drug within 14 days before the start of trial treatment
* Other malignancy currently being treated or likely to need treatment in next 6 months with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ, surgically removed malignancies or malignancies definitively treated with chemotherapy, XRT and/or surgery with no evidence of active malignancy or not anticipated to need treatment in next 6 months or malignancies on maintenance therapy (e.g. tamoxifen for breast cancer) will be allowed after discussion and approval by both MPIs
* Pregnant or breastfeeding females
* Known current alcohol or drug abuse
* Clinically significant cardiovascular disease within the past 6 months (e.g. percutaneous intervention, coronary artery bypass graft, documented NYHA class III/IV cardiac heart failure, unstable angina or MI, poorly controlled atrial or ventricular arrhythmia) as determined by the investigator
* Any psychiatric condition that would prohibit the understanding or rendering of informed consent
* Legal incapacity or limited legal capacity to sign consent and/or participate in the trial
* Any condition deemed by the investigator to make the patient a poor candidate for clinical trial and/or treatment with investigational agents.
* Previous exposure to the investigational agent (danvatirsen) or to other STAT3 inhibitors

Contacts and Locations

Study Contact

Aditi Shastri, MBBS

CONTACT

718-920-4826

ashastri@montefiore.org

Principal Investigator

Aditi Shastri, MBBS

PRINCIPAL_INVESTIGATOR

Montefiore Medical Center

Study Locations (Sites)

Montefiore Medical Center

Bronx, New York, 10467

United States

M.D. Anderson Cancer Center, Department of Leukemia

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Montefiore Medical Center

Aditi Shastri, MBBS, PRINCIPAL_INVESTIGATOR, Montefiore Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-05-08

Study Completion Date2028-07

Study Record Updates

Study Start Date2024-05-08

Study Completion Date2028-07

Terms related to this study

Additional Relevant MeSH Terms

AML/MDS
Acute Myeloid Leukemia
Myelodysplastic Syndromes