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

July 1, 2022 updated by: Jane Liesveld, University of Rochester

A Phase I/II Study of Decitabine in Combination With Sequential Rapamycin or Ribavirin in High Risk AML Patients

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
27

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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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Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Median Overall Survival
Time Frame: 2 years
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Blast Percentage in Peripheral Blood
Time Frame: baseline and four weeks
bone marrow aspirate and biopsy exam
baseline and four weeks
Mean Change in Blast Percentage in Marrow
Time Frame: baseline and four weeks
Complete blood count with differential.
baseline and four weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Rochester

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jane Liesveld, MD, University of Rochester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 14, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 10, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 5, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 1, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 48721
  • ULEU13049 (Other Identifier: University of Rochester)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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