Study of Decitabine in Combination With Sequential Rapamycin or Ribavirin in High Risk AML Patients

Sponsor
University of Rochester (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02109744
Collaborator
(none)
24
Enrollment
1
Location
2
Arms
96.9
Anticipated Duration (Months)
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the response to chemotherapy with the drug decitabine combined with rapamycin in the treatment of relapsed or refractory acute myeloid leukemia in patients of all ages, and in the treatment of newly diagnosed leukemia in those who are older than 65 when diagnosed.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1/Phase 2

Detailed Description

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 Design

Study Type:
Interventional
Anticipated Enrollment :
24 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 :
Feb 1, 2014
Anticipated Primary Completion Date :
Mar 1, 2022
Anticipated Study Completion Date :
Mar 1, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Decitabine followed by rapamycin

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).

Drug: Decitabine
Other Names:
  • Dacogen
  • 5-aza-2'-deoxycytidine
  • Experimental: Decitabine followed by ribavirin

    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).

    Drug: Decitabine
    Other Names:
  • Dacogen
  • 5-aza-2'-deoxycytidine
  • Outcome Measures

    Primary Outcome Measures

    1. change in blast percentage in the bone marrow [four weeks]

      bone marrow aspirate and biopsy exam

    Secondary Outcome Measures

    1. change in blast percentage in peripheral blood [four weeks]

      Complete blood count with differential.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    4.1.1 Age >/= 18 4.1.2 Diagnosis of AML according to World Health Organization (WHO) criteria except acute promyelocytic leukemia AND 4.1.3 Refractory AML defined as failure to achieve Complete Remission (CR) after 2 cycles of induction chemotherapy or persistence of

    40% bone marrow blasts after one cycle of chemotherapy induction OR 4.1.4 Relapsed AML defined as any evidence of disease recurrence after achieving a documented first or greater Complete Remission (CR) OR 4.1.5 Relapsed AML after stem cell transplantation. 90 days (since stem cell infusion) must have elapsed between transplant and emergence of recurrent AML OR 4.1.6 Newly diagnosed AML in a patient >65 years old not considered fit for standard 7+ 3 chemotherapy or who declines such therapy after discussion of therapeutic options available.

    4.1.7 Eastern Cooperative Oncology Group (ECOG) performance status <3

    Exclusion Criteria:

    4.2.1 Abnormal renal function as evidenced by a calculated creatinine clearance ≤ 30 ml/min (Cockcroft-Gault formula (Appendix 2) 4.2.2 Abnormal liver function: Bilirubin >2.0 mg/dl, transaminase(s) more than 2.5x the upper limits of normal 4.2.3 Active systemic infection not responding to antibiotics 4.2.4 Known diagnosis of human immunodeficiency virus infection (HIV) 4.2.5 Patients who are post-allogeneic transplantation should not have active Graft vs. Host Disease (GVHD) greater than grade 1 of skin at time of enrollment. They may have had donor lymphocyte infusion (DLI) but not within 4 weeks of beginning the study.

    4.2.6 Pregnant or breastfeeding female subjects 4.2.7 Known or suspected Central Nervous System (CNS) leukemia involvement; past involvement is not an exclusion.

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    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of RochesterRochesterNew YorkUnited States14642

    Sponsors and Collaborators

    • University of Rochester

    Investigators

    • Principal Investigator: Jane Liesveld, MD, University of Rochester

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Jane Liesveld, Principal INvestigator, University of Rochester
    ClinicalTrials.gov Identifier:
    NCT02109744
    Other Study ID Numbers:
    • 48721
    • ULEU13049
    First Posted:
    Apr 10, 2014
    Last Update Posted:
    Dec 10, 2021
    Last Verified:
    Dec 1, 2021

    Study Results

    No Results Posted as of Dec 10, 2021