TerminatedPhase 1/2

A Phase 1b/2 Study of Alvocidib Plus Decitabine or Azacitidine in Patients With MDS

Stopped: The sponsor decided not to continue the study based on the overall company strategy in AML.

United States20 participantsStarted 2018-08-29

Plain-language summary

Alvocidib, a cyclin-dependent kinase 9 (CDK 9) inhibitor, in time-sequential therapy demonstrated significant clinical activity in secondary AML patients with prior MDS. Patients with IPSS-R intermediate and above MDS have an increased risk of developing AML and may be treated with the same chemotherapy regimens used in patients with AML. Eight Phase I or II clinical trials have been completed in patients with AML, totaling more than 400 patients with both relapsed/refractory or newly diagnosed AML. Preclinical studies have demonstrated that decitabine exposure increased the expression of NOXA, which is a specific antagonist of the survival factor MCL 1. Pharmacologic downregulation of MCL-1 via CDK 9 inhibition, as well as upregulation of the MCL-1 antagonist, NOXA, following decitabine exposure may result in enhanced antileukemic activity in MCL-1-dependent malignancies.

Who can participate

Age range18 Years

SexALL

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Inclusion criteria

✓. Aged ≥18 years
✓. Phase 1b Dose Escalation: Patients with previously untreated MDS and patients with MDS who received fewer than six (6) cycles of previous HMAs. Phase 1b Expansion: Untreated patients with de novo or secondary MDS. Phase 2: Untreated patients with de novo or secondary MDS
✓. Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score ≤2 at enrollment
✓. Provide written informed consent prior to any study-related procedure. (In the event that the patient is re-screened for study participation or a protocol amendment alters the care of an ongoing patient, a new informed consent form must be signed.)
✓. Patients with a life expectancy of ≥3 months (90 days)
✓. Patients with adequate major organ functions meeting the following criteria on the basis of laboratory data within 4 weeks (28 days) before enrollment (if multiple data are available, most recent data during the period):
✓. Serum creatinine: ≤1.8× the upper limit of the normal (ULN) range
✓. Total bilirubin: ≤2× the ULN

Exclusion criteria

What they're measuring

Number of Participants With Adverse Events and Serious Adverse Events

Timeframe: From the time of first dose to 30 days after the last dose, an average of 33.7 weeks.

Tolerability of Alvocidib as Evaluated by Incidence of Dose Limiting Toxicities (DLTs) as Observed in Cycle 1

Timeframe: Cycle 1 (28 days)

Trial details

NCT IDNCT03593915

SponsorSumitomo Pharma America, Inc.

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2021-08-16

Results submitted2022-09-22

View on ClinicalTrials.gov More Myelodysplastic Syndromes (MDS) trials