Study of Decitabine in Combination With Sequential Rapamycin or Ribavirin in High Risk AML Patients (AML)
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|ClinicalTrials.gov Identifier: NCT02109744|
Recruitment Status : Recruiting
First Posted : April 10, 2014
Last Update Posted : November 26, 2018
|Condition or disease||Intervention/treatment||Phase|
|Acute Myelogenous Leukemia||Drug: Decitabine||Phase 1 Phase 2|
To determine the efficacy of decitabine followed by Rapamycin in previously untreated elderly patients not able to receive standard chemotherapy or in patients with relapsed or refractory AML, through measurement of Complete Remission (CR), Complete Remission Incomplete Platelet Recovery (CRp), Partial Remission (PR), and event free and overall survival (Arm A).
To determine the safety of administration of decitabine with escalating doses of Ribavirin in elderly leukemia patients or patients with relapsed/refractory disease with M4/M5 subtypes anticipated to express high eukaryotic translation initiation factor 4E (eIF4E) at diagnosis (Arm B).
To establish effect of these sequential treatments on expression of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt /mTOR) pathway proteins and on eukaryotic translation initiation factor 4E (eIF4E) activation through Western blot and phospho-flow methodologies.
To correlate the clinical response with baseline expression of phospho-p70S6 Kinase/phosphorylated protein kinase B (pAKT) and with the in vitro inhibitory effects of mammalian target of rapamycin (mTOR) inhibition with rapamycin or ribavirin on the level of downstream effectors.
To determine whether a leukemia stem cell phenotype is inhibited by the sequential administration of decitabine/rapamycin or decitabine/ribavirin.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of Decitabine in Combination With Sequential Rapamycin or Ribavirin in High Risk AML Patients|
|Actual Study Start Date :||February 2014|
|Estimated Primary Completion Date :||June 2019|
|Estimated Study Completion Date :||December 2020|
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Rapamycin 6mg (loading dose) will be administered on day 6; thereafter 2 mg/day on days 11-22 in cycle 1 and on days 6-22 in subsequent cycles. (Arm A: for patients with non-morphologic M4/M5 subtypes).
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes).
- change in blast percentage in the bone marrow [ Time Frame: four weeks ]bone marrow aspirate and biopsy exam
- change in blast percentage in peripheral blood [ Time Frame: four weeks ]Complete blood count with differential.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02109744
|Contact: Jane Liesveld, MD||585-275-4099||Jane_Liesveld@urmc.rochester.edu|
|United States, New York|
|University of Rochester||Recruiting|
|Rochester, New York, United States, 14642|
|Contact: Haley Misch 585-275-9485 Haley_Misch@urmc.rochester.edu|
|Contact: Robin Boerman 585-273-1507 Robin_Boerman@urmc.rochester.edu|
|Principal Investigator: Jane Liesveld, MD|
|Sub-Investigator: Kristen O'Dwyer, MD|
|Principal Investigator:||Jane Liesveld, MD||University of Rochester|