Active — Not RecruitingPhase 1

Navitoclax in Relapsed or Refractory High-Risk Myelodysplastic Syndrome

United States6 participantsStarted 2023-01-12

Plain-language summary

This 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.

Who can participate

Age range18 Years

SexALL

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Inclusion Criteria: * Provide signed and dated informed consent form * Willing to comply with all study procedures and be available for the duration of the study * Male or female, aged 18 years or older * Must have myelodysplastic syndrome with Revised International Prognostic Score (IPSS-R) of at least 3 and have been previously treated with hypomethylating agent (HMA) (azacitidine or decitabine) and venetoclax for at least 2 cycles. Patients in the phase I portion of the trial may be enrolled if they have not received venetoclax with HMA therapy * Prior hematopoietic stem cell transplant will be allowed if 90 or more days has passed since the date of transplant to day 1 of cycle 1 and patients are no longer taking immunosuppressive agents * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 * Must be able to swallow pills whole * Creatinine clearance \>= 40 mL/min, calculated with the use of the 24-hour creatinine clearance or modified Cockcroft-Gault equation * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN) * Total bilirubin =\< 1.5 x ULN (or =\< 3 x ULN for patients with documented Gilbert syndrome) * Coagulation: activated partial thromboplastin time (aPTT) and international normalized ratio (INR) =\< 1.5 x ULN * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potentia…

What they're measuring

Maximally Tolerated Dose (MTD) of Navitoclax in Combination with Venetoclax and Decitabine (Phase I)

Timeframe: Within 30 days of the first dose of study treatment

Complete Response (CR) Rate (Phase II)

Timeframe: Up to cycle 4, an average of 4 months

Trial details

NCT IDNCT05564650

SponsorThomas Jefferson University

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2024-05-03