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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05564650
Other study ID # 22P.205
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date January 12, 2023
Est. completion date July 2025

Study information

Verified date January 2024
Source Thomas Jefferson University
Contact Gina Keiffer, MD
Phone 215-503-0432
Email gina.keiffer@jefferson.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase Ib/II trial tests the safety, side effects, and best dose of navitoclax in combination with venetoclax and decitabine in treating patients with higher risk myelodysplastic syndrome (MDS) that has come back after initial treatment or was not responsive to initial treatment. This study will also look at the effectiveness of the treatment combination and patient's quality of life while on these medications. Navitoclax is an oral drug that works as an inhibitor of the BCL-2 family of proteins, which are often overly expressed in a wide variety of cancers and are linked to tumor drug resistance. This drug blocks some of the enzymes that keep cancer cells from dying. Venetoclax is an oral drug that works as an inhibitor of BCL-2 proteins that works very similarly to navitoclax by blocking the action of a certain proteins in the body that helps cancer cells survive which helps to kill cancer cells. Decitabine is an intravenous drug. It is a hypomethylating agent which means it interferes with deoxyribonucleic acid (DNA) methylation. DNA methylation is a major factor that regulates gene expression in cells, and an increase in DNA methylation can block the genes that regulate cell division and growth. When these genes are blocked the overall result allows or promotes cancer as there is no control over cell growth. Decitabine stops cells from making DNA and may kill cancer cells. Participation in this trial may improve the understanding of both chemotherapy response in MDS and mechanisms of resistance to current therapies.


Description:

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Study Design


Related Conditions & MeSH terms


Intervention

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Locations

Country Name City State
United States Sidney Kimmel Cancer Center at Thomas Jefferson University Philadelphia Pennsylvania

Sponsors (2)

Lead Sponsor Collaborator
Thomas Jefferson University AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Expression levels of anti-apoptotic BCL-2 family members (Phase II) Assessed by intracellular flow cytometry to determine predictive value for response. Data will be analyzed with FlowJo software. At baseline and after triplet therapy, assessed up to 2 years from enrollment of the last patient
Other Single cell gene expression (Phase II) Ribonucleic acid (RNA) will be isolated from pre-treatment and post-treatment CD19+ cells and used for gene expression profiles (microarray or RNA-Seq). At baseline and after triplet therapy, assessed up to 2 years from enrollment of the last patient
Primary Maximally tolerated dose (MTD) of navitoclax in combination with venetoclax and decitabine (Phase I) The final observed rate of dose limiting toxicity (DLT) will be calculated and from this the MTD will be determined. Within 30 days of the first dose of study treatment
Primary Complete response (CR) rate (Phase II) A 90% confidence interval will be computed for the CR rate by cycle 4. Up to cycle 4 (each cycle is 28 days)
Secondary Number of dose-limiting toxicities (Phase I) Number of dose-limiting toxicities (Phase I) Within 30 days of the first dose of study treatment
Secondary Marrow Complete Response rate (mCR) (Phase II) Defined as per International Working Group (IWG) criteria. Up to 2 years from enrollment of the last patient
Secondary Hematologic Improvement (HI) rate (Phase II) Defined as per IWG criteria. Up to 2 years from enrollment of the last patient
Secondary Leukemia free survival (LFS) (Phase II) Defined as per IWG criteria From the date of randomization to the date of diagnosis of AML or death from any cause, whichever came first, assessed up to 2 years from enrollment of the last patient
Secondary Overall survival (OS) (Phase II) Will be estimated using the Kaplan-Meier method, and the median OS along with its corresponding 95% confidence interval will be reported. From study registration to death from any cause, assessed up to 2 years from enrollment of the last patient
Secondary Change in quality of life (QOL) (Phase II) Will be assessed by European Organization for Research and Treatment of Cancer (EORTC Quality of Life Questionnaire [EORTC QLQ-C30] and Patient Reported Outcomes Measurement Information System [PROMIS-Fatigue]). At baseline
Secondary Change in quality of life (QOL) (Phase II) Will be assessed by Patient Reported Outcomes Measurement Information System [PROMIS-Fatigue]). At 4 months
Secondary Change in quality of life (QOL) (Phase II) Will be assessed by European Organization for Research and Treatment of Cancer (EORTC Quality of Life Questionnaire [EORTC QLQ-C30] At study completion, assessed up to 2 years from enrollment of the last patient
Secondary Change in quality of life (QOL) (Phase II) Will be assessed by Patient Reported Outcomes Measurement Information System [PROMIS-Fatigue]). assessed up to 2 years from enrollment of the last patient
Secondary Change in quality of life (QOL) (Phase II) Will be assessed by European Organization for Research and Treatment of Cancer (EORTC Quality of Life Questionnaire [EORTC QLQ-C30] study completion, assessed up to 2 years from enrollment of the last patient
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