Physical Conditioning and Decitabine for Newly Diagnosed AML Patients Age ≥ 60

NCT02234037 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: IRB00064866WINSHIP2381-12
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

STUDY BACKGROUND AND PURPOSE: Acute myelogenous leukemia (AML) is a common type of blood cancer in adults, and is more common with increasing age. AML is harder to treat in older patients, with typically poor responses to standard chemotherapy. Patients with AML are typically given intensive induction chemotherapy, but many older patients cannot tolerate the side effects of this therapy. Decitabine has been shown to be active and better tolerated in frail patients with AML; however, most patients still relapse. Recent studies suggest that improving the performance status and fitness of older AML patients prior to induction chemotherapy may help to lessen side effects. This study will test the combination of decitabine treatment with physical exercise in elderly patients with AML who are not candidates for standard induction chemotherapy. STUDY DESCRIPTION: This is a pilot study to test the combination of decitabine treatment with an 8-week physical exercise program in AML patients ≥ 60 years of age who are not candidates for standard induction chemotherapy. Patients who are eligible to take part must give their written agreement before they can be enrolled. This study will enroll 20 patients who are not candidates for standard induction chemotherapy. Patients will begin an 8-week program of physical exercise, including 2-3 sessions per week supervised by a physical therapist. During this 8-week period, patients will be given 2 cycles of decitabine therapy (daily infusion for 5 consecutive days of a 28-day cycle). Patients will be followed to assess the safety and tolerability of the program. Patients will also give blood samples that will be used to assess their response to treatment. Patients will be evaluated for their physical fitness before and after the 8-week exercise program and will complete questionnaires to assess their quality of life before and after the program.

Conditions

Leukemia

Keywords

AML

Outcome Measures

Primary Outcomes (4)

• Performance status

  ECOG performance status is assessed before, at 4 weeks and 8 weeks from start of the intervention.

  Up to 8 weeks

• Proportion of patients with 25% improvement in fitness scores

  Patients will be asked to answer questions on the 36-item (SF-36) fitness scoring system and the FACIT-Leu fatigue scale at baseline, 4 weeks and 8 weeks of the study.

  Up to 8 weeks

• Function

  Function will be measured using the 6-meter walk test, timed Up and Go test, grip strength and lower limb strength.

  8 weeks

• Activity

  Activity will be based on daily stepping activity (measured using step activity monitors), endurance (distance ambulated in 3-minutes), and duration of aerobic exercise (treadmill walking or cycling) at 50% heart rate and/or Borg score \> 5.

  8 weeks

Secondary Outcomes (3)

• Number of patients with adverse events related to the intervention.

  8 weeks

• Response to treatment

  18 months

• Quality of life and depression scores among study subjects before and after the 8-week exercise program

  8 weeks

Study Arms (1)

Decitabine and Exercise

EXPERIMENTAL

8-week program of physical conditioning and decitabine treatment in newly diagnosed AML patients ≥ 60 years of age who are not candidates for standard induction chemotherapy.

Drug: Decitabine; Behavioral: Exercise

Interventions

Decitabine DRUG

Decitabine will be administered intravenously at dose of 20mg/m² on 5 consecutive days every 28 days (1 cycle = 28 days) for a total of 2 cycles according to standard practice. Cycle 2 will proceed on time despite cytopenias, given that patients are not expected to be in remission after only 1 cycle of decitabine.

Also known as: Dacogen

Decitabine and Exercise

Exercise BEHAVIORAL

Each patient will participate in 2-3 exercise sessions per week supervised by a physical therapist. Each exercise session will comprise \> 10 minutes of muscle strengthening, \> 10 minutes of aerobic exercise (treadmill walking or cycling), \> 10 minutes of stretching/range of motion exercises, and up to 10 minutes of individualized functional exercise (determined based on patient's reported deficits/targets in activities of daily living).

Decitabine and Exercise

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of AML including de novo, secondary, or with an antecedent hematologic disorder (AHD) according to the World Health Organization (WHO) criteria
• Age ≥ 60 years
• Patient not eligible for (immediate) standard induction chemotherapy based on the opinion of the treating physician and the frailty score
• Provide signed written informed consent
• Be able to comply with study procedures and follow-up examinations
• Adequate heart function with echocardiogram demonstrating ejection fraction ≥ 45% with no evidence of systolic dysfunction
• Adequate renal and hepatic function:
• Total bilirubin ≤ 2x institutional Upper Limit of Normal (ULN); and
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3x ULN; and
• Serum creatinine ≤ 2 times the upper limit of normal
• ECOG performance \< 4
• Patients with a history of carcinoma in remission (on no therapy or on hormonal therapy for the adjuvant treatment of breast carcinoma or prostate carcinoma) are included in the study.

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia (APL, French-American-British \[FAB\] classification M3 or WHO classification of APL with t(15;17)(q22;q12)), (PML/retinoic acid receptor alpha \[RARa\] and variants)
• Prior treatment with decitabine for myelodysplastic syndrome (MDS) or AML
• Relapsed or refractory AML
• Rapidly doubling white cell count uncontrolled with hydroxyurea
• Coronary artery disease with angina limiting exercise capability
• Joint disease limiting exercise capability
• Investigational agent received within 30 days prior to the first dose of study drug. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to Grade 2 or less prior to first dose of study drug
• Psychiatric disorders that would interfere with consent, study participation, or follow-up
• Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
• Any other severe concurrent disease, or serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo the proposed therapy
• No social support or inability to attend study-related visits
• Carcinoma requiring systemic chemotherapy or radiation therapy

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Leukemia

Interventions

Decitabine; Exercise

Condition Hierarchy (Ancestors)

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; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Martha L Arellano, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 27, 2014
• First Posted: September 9, 2014
• Study Start: November 1, 2013
• Primary Completion: February 1, 2016
• Study Completion: May 1, 2016
• Last Updated: January 30, 2017

Record last verified: 2017-01

Locations

US (1)