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

NCT02109744 | Completed Phase 1 Results DMC

• 2 other identifiers: 48721ULEU13049
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myelogenous Leukemia

Outcome Measures

Primary Outcomes (1)

• Median Overall Survival

  2 years

Secondary Outcomes (2)

• Blast Percentage in Peripheral Blood

  baseline and four weeks

• Mean Change in Blast Percentage in Marrow

  baseline and four weeks

Study Arms (2)

Decitabine followed by rapamycin

EXPERIMENTAL

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

Decitabine followed by ribavirin

EXPERIMENTAL

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

Interventions

Decitabine DRUG

Also known as: Dacogen, 5-aza-2'-deoxycytidine

Decitabine followed by rapamycin; Decitabine followed by ribavirin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status \<3

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester

Rochester, New York, 14642, United States

Location

Related Publications (1)

• Liesveld JL, Baran A, Azadniv M, Misch H, Nedrow K, Becker M, Loh KP, O'Dwyer KM, Mendler JH. A phase II study of sequential decitabine and rapamycin in acute myelogenous leukemia. Leuk Res. 2022 Jan;112:106749. doi: 10.1016/j.leukres.2021.106749. Epub 2021 Nov 11.

  PMID: 34839054 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Jane Liesveld
• Organization: University of Rochester

Jane_Liesveld@urmc.rochester.edu

585 - 275 - 5823

Study Officials

• Jane Liesveld, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal INvestigator

Study Record Dates

• First Submitted: October 14, 2013
• First Posted: April 10, 2014
• Study Start: March 1, 2014
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: July 5, 2022
• Results First Posted: July 5, 2022

Record last verified: 2022-07

Locations

US (1)