Evaluate the Efficacy of Armodafinil for Patients With B-cell Lymphoma and Severe Fatigue

A Randomized, Double-Blind, Placebo-Controlled Pilot Study to Evaluate the Efficacy of Armodafinil for Patients With B-cell Lymphoma and Severe Fatigue Undergoing Standard R-CHOP Chemotherapy or in Remission Following Chemo and/or Radiation

To determine whether armodafinil is more effective than placebo in reducing fatigue.

Study Overview

• Status: Withdrawn
• Conditions: B-cell Lymphoma; Fatigue
• Intervention / Treatment: Drug: Armodafinil; Drug: placebo

Detailed Description

Aims will be analyzed separately as stratified by treatment arm (chemotherapy treatment arm vs. post-treatment remission arm).

Primary Objective:

• To determine whether armodafinil is more effective than placebo in reducing fatigue as measured by the change in scores from the FACT-Fatigue reported at study entry, week 7 of study treatment, and study completion (week 13).

Secondary Objectives:

• To determine whether armodafinil is more effective than placebo in reducing fatigue as measured by standard actigraphy summary statistics including total sleep time (TST), wake after sleep onset (WASO), sleep latency, number of awakenings, daytime sleep time, mean daytime activity, peak activity, acrophase, and circadian mesor at week 1 of screening, week 7 of study treatment, and study completion (week 13).
• To determine whether armodafinil is more effective than placebo in improving work quality as measured by the change in scores from the WLQ© reported at study entry (week 1) and study completion (week 13).
• To determine whether armodafinil is more effective than placebo in reducing fatigue as measured by the change in activity patterns with actigraphy using applied functional data analysis during week 1 of screening, week 7 of study treatment, and study completion (week 13).
• To evaluate whether measured cytokines (IL-2, IL-6, IL-10, TNF-α, and TGF-α) are elevated at baseline.
• To evaluate whether measured cytokines (IL-2, IL-6, IL-10, TNF-α, and TGF-α) change from the time of study entry to study completion.
• To assess whether cytokine levels (IL-2, IL-6, IL-10, TNF-α, and TGF-α) correlate with circadian patterns in wrist actigraphy and self-described reports of fatigue as measured by the FACT-Fatigue at baseline and study completion.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria for both arms:

• Age ≥ 18 with diagnosis of B-cell lymphoma
• Average score of ≥ 7 on daily worst fatigue severity assessment from the BFI questionnaire during screening
• Able to demonstrate appropriate use of the wrist actigraphy device and to complete questionnaires
• ECOG performance status 0-2
• Laboratory values:
• Hemoglobin ≥ 10 g/dL
• Total Bilirubin ≤ 1.5 x institutional ULN
• AST/ALT ≤ 2.5 x institutional ULN
• Creatinine ≤ 1.5 x institutional ULN
• Albumin ≥ 3.5 g/dl
• Life expectancy > 6 months
• IRB-approved informed consent form must be signed before any protocol-specific screening procedures are performed.

Inclusion criteria for patients undergoing R-CHOP chemotherapy:

• Scheduled to receive 6 cycles of standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy as first-line treatment

Inclusion criteria for patients in remission following chemotherapy and/or radiotherapy:

• May have received one prior regimen of chemotherapy and/or radiotherapy
• Adequate response to upfront chemotherapy and/or radiotherapy
• Indolent lymphomas - must have achieved a partial or complete response with no immediate plans for further treatment

• Aggressive lymphomas - must have achieved a complete response:

  • ≥ 4 weeks since completion of chemotherapy
  • ≥ 8 weeks since completion of radiotherapy
  • ≤ 18 months since completion of chemotherapy or radiotherapy

Exclusion Criteria for both arms:

• Uncontrolled medical and/or psychiatric condition that may cause fatigue or that the PI feels is clinically significant and might adversely affect patient safety (such as sleep disorders, moderate/severe depression, metabolic/endocrine abnormalities, infections)
• History of clinically significant cardiac disorders, such as left ventricular hypertrophy or mitral valve prolapse experienced in conjunction with receiving CNS stimulants
• History of serious skin reactions, such as serious rash or Stevens-Johnson Syndrome
• Concurrent stimulant medication
• Any other active malignancy within the past 3 years except cervical carcinoma in situ and non-melanoma skin cancers
• Known CNS involvement by lymphoma
• Cachexia
• Use of opioids at time of randomization
• Known sensitivity to modafinil and/or armodafinil

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Post treatment remission armodafinil; Armodafinil 150 mg/day for 13 weeks	Drug: Armodafinil; Armodafinil 150 mg/day for 13 weeks; Other Names: Nuvigil
Placebo Comparator: Post treatment remission placebo; Placebo 150mg/day for 13 weeks	Drug: placebo; Placebo 150mg/day for 13 weeks
Experimental: Chemotherapy armodafinil; Armodafinil 150 mg/day for 13 weeks	Drug: Armodafinil; Armodafinil 150 mg/day for 13 weeks; Other Names: Nuvigil
Placebo Comparator: Chemotherapy placebo; Placebo 150mg/day for 13 weeks	Drug: placebo; Placebo 150mg/day for 13 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine whether armodafinil is more effective than placebo in reducing fatigue as measured by the change in scores from the FACT-Fatigue reported at study entry, week 7 of study treatment, and study completion (week 13).	13 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine whether armodafinil is more effective than placebo in improving work quality as measured by the change in scores from the WLQ© reported at study entry (week 1) and study completion (week 13).	13 weeks
To determine whether armodafinil is more effective than placebo in reducing fatigue as measured by standard actigraphy summary statistics will be done at week 1 of screening, week 7 of study treatment, and study completion (week 13).	13 weeks
To determine whether armodafinil is more effective than placebo in reducing fatigue as measured by actigraphy using applied functional data analysis during week 1 of screening, week 7 of study treatment, and study completion (week 13).	13 weeks
To evaluate whether measured cytokines (IL-2, IL-6, IL-10, TNF-α, and TGF-α) are elevated at baseline.	13 weeks
To evaluate whether measured cytokines (IL-2, IL-6, IL-10, TNF-α, and TGF-α) change from the time of study entry to study completion.	13 weeks
To assess whether cytokine levels (IL-2, IL-6, IL-10, TNF-α, and TGF-α) correlate with circadian patterns in wrist actigraphy and self-described reports of fatigue as measured by the FACT-Fatigue at baseline and study completion.	13 weeks

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Nina Wagner-Johnston, M, Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Anticipated): June 1, 2012
• Study Completion (Anticipated): June 1, 2012

Study Registration Dates

• First Submitted: January 6, 2010
• First Submitted That Met QC Criteria: January 6, 2010
• First Posted (Estimate): January 7, 2010

Study Record Updates

• Last Update Posted (Estimate): July 23, 2013
• Last Update Submitted That Met QC Criteria: July 22, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Fatigue; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Modafinil
• Other Study ID Numbers: 09-1896