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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
Sponsor:
Information provided by (Responsible Party):
Jane Liesveld, University of Rochester

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 disease Intervention/treatment Phase
Acute Myelogenous Leukemia Drug: Decitabine 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 Type : Interventional  (Clinical Trial)
Estimated 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 : February 2014
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: A
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: B
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




Primary Outcome Measures :
  1. change in blast percentage in the bone marrow [ Time Frame: four weeks ]
    bone marrow aspirate and biopsy exam


Secondary Outcome Measures :
  1. change in blast percentage in peripheral blood [ Time Frame: four weeks ]
    Complete blood count with differential.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

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


Contacts
Contact: Jane Liesveld, MD 585-275-4099 Jane_Liesveld@urmc.rochester.edu

Locations
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         
Sponsors and Collaborators
University of Rochester
Investigators
Principal Investigator: Jane Liesveld, MD University of Rochester

Responsible Party: Jane Liesveld, Principal INvestigator, University of Rochester
ClinicalTrials.gov Identifier: NCT02109744     History of Changes
Other Study ID Numbers: 48721
ULEU13049 ( Other Identifier: University of Rochester )
First Posted: April 10, 2014    Key Record Dates
Last Update Posted: November 26, 2018
Last Verified: November 2018

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Ribavirin
Decitabine
Azacitidine
Sirolimus
Everolimus
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Anti-Bacterial Agents
Antibiotics, Antineoplastic
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs