Back to resultsATRA, Celecoxib, and Itraconazole as Maintenance
Primary Purpose
Relapsed Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ATRA
Celecoxib
Itraconazole
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed Multiple Myeloma focused on measuring Relapsed multiple myeloma
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of relapsed multiple myeloma
- Recent salvage transplant (≤ 6 months but ≥ 45 days post-transplant prior to study enrollment) for relapse
- 18-75 years of age at the time of study entry
- Platelet count ≥70K/mm3 un-transfused
- Resolution of all transplant-related toxicity to ≤ grade 2 per CTCAE v.4
- Left ventricular ejection fraction as measured by ECHO or MUGA should be ≥ 40%
- Creatinine of ≤ 2 mg/dl and a calculated GFR of >50mL/min/1.73m2
- A total bilirubin, ALT, AST, and alkaline phosphatase of ≤ 2 ULN
- Performance status of 0-2 based on the ECOG criteria. Patients with performance status 3 or 4, based solely on bone pain, are also eligible, provided that there is a source document to verify this
- Prospective study participants must be informed of the investigational nature of the study and must have signed an IRB-approved informed consent form in accordance with institutional and federal guidelines
Exclusion Criteria:
- Prior allogeneic transplant
- Greater than grade 2 motor neuropathy or greater than grade 3 sensory neuropathy at screening
- Uncontrolled diabetes
- Recent (< 6 months) myocardial infarction, unstable angina, CABG or stent placement in the last 2 years, difficult-to-control congestive heart failure, uncontrolled hypertension (systolic blood pressure > 160 mm or a diastolic BP > 110 mm under normal conditions and while on appropriate anti-hypertensive medications), or difficult- to-control cardiac arrhythmias
- Evidence of QT prolongation and/or torsades de pointes (TdP) on EKG.
- Any co-morbid condition that poses a greater threat to the patient's life expectancy than the recurrent myeloma
- No concurrent malignancy with a life expectancy of less than two years, or one that requires ongoing chemotherapeutic intervention at screening
- Presence of an infection that requires intravenous antibiotics
- Pregnant or nursing females. Any patient of reproductive potential may not participate unless he/she has agreed to use an effective contraceptive method as covered during the informed consent process
- Known history of an HIV seropositive test
Sites / Locations
- University of Iowa Hospitals and Clinics
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ATRA/celecoxib/itraconazole
Arm Description
All maintenance drugs will be given on days 1-21 of each cycle, followed by 14 days off treatment. Cycles will be repeated every 35 days (+/- 3 days) for a total of five cycles. Each patient enrolled will receive ATRA 20mg twice per day by mouth. Dose modifications are not allowed unless excessive toxicity occurs. In this case, ATRA will be de-escalated by 50% to 10mg twice per day by mouth. The dose of celecoxib for all patients enrolled will be 400 mg twice per day by mouth. If creatinine level increases to more than 2 mg/dl and cannot be corrected by increased oral fluid intake or other measures, the dose of celecoxib will be decreased by 50%. If creatinine level does not drop below 2 mg/dl on the reduced dose, celecoxib will be discontinued. The dose of itraconazole for all patients enrolled will be 200 mg twice per day by mouth. Dose modifications are not allowed.
Outcomes
Primary Outcome Measures
Number of Participants with Adverse Events as a Measure of Safety
Secondary Outcome Measures
Blood and Bone Marrow Aspirate Samples as a measure of changes to the MMSC (multiple myeloma stem cell) fraction.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02401295
Brief Title
ATRA, Celecoxib, and Itraconazole as Maintenance
Official Title
An Open-Label Phase I Trial to Evaluate the Safety and Tolerability of ATRA, Celecoxib, and Itraconazole Administered As Maintenance Treatment Post-Autologous Transplantation in Relapsed Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
November 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Iowa
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability associated with the combination of ATRA/celecoxib/itraconazole as maintenance therapy given after an autologous stem cell transplant in relapsed multiple myeloma patients.
Detailed Description
Primary objective:
To evaluate safety and tolerability associated with the combination of ATRA/ celecoxib/itraconazole given after a salvage transplant for relapsed myeloma in 25 patients in a cycle schedule consisting of three weeks of treatment followed by a rest period of two weeks for a total of five cycles. Subjects will be evaluable only if they have received at least one dose of maintenance treatment. The salvage transplant is not part of this study.
Secondary objective:
To explore changes in frequency and molecular signature in the multiple myeloma stem cell (MMSC) fraction based on flow-cytometric assays and gene expression profiling before and after the experimental treatment and to correlate outcome with expression levels of RARα2 at time of relapse.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed Multiple Myeloma
Keywords
Relapsed multiple myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ATRA/celecoxib/itraconazole
Arm Type
Experimental
Arm Description
All maintenance drugs will be given on days 1-21 of each cycle, followed by 14 days off treatment. Cycles will be repeated every 35 days (+/- 3 days) for a total of five cycles.
Each patient enrolled will receive ATRA 20mg twice per day by mouth. Dose modifications are not allowed unless excessive toxicity occurs. In this case, ATRA will be de-escalated by 50% to 10mg twice per day by mouth.
The dose of celecoxib for all patients enrolled will be 400 mg twice per day by mouth. If creatinine level increases to more than 2 mg/dl and cannot be corrected by increased oral fluid intake or other measures, the dose of celecoxib will be decreased by 50%. If creatinine level does not drop below 2 mg/dl on the reduced dose, celecoxib will be discontinued.
The dose of itraconazole for all patients enrolled will be 200 mg twice per day by mouth. Dose modifications are not allowed.
Intervention Type
Drug
Intervention Name(s)
ATRA
Other Intervention Name(s)
All-Trans-Retinoic Acid, tretinoin
Intervention Type
Drug
Intervention Name(s)
Celecoxib
Other Intervention Name(s)
Celebrex
Intervention Type
Drug
Intervention Name(s)
Itraconazole
Other Intervention Name(s)
Sporanox, Onmel
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events as a Measure of Safety
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Blood and Bone Marrow Aspirate Samples as a measure of changes to the MMSC (multiple myeloma stem cell) fraction.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of relapsed multiple myeloma
Recent salvage transplant (≤ 6 months but ≥ 45 days post-transplant prior to study enrollment) for relapse
18-75 years of age at the time of study entry
Platelet count ≥70K/mm3 un-transfused
Resolution of all transplant-related toxicity to ≤ grade 2 per CTCAE v.4
Left ventricular ejection fraction as measured by ECHO or MUGA should be ≥ 40%
Creatinine of ≤ 2 mg/dl and a calculated GFR of >50mL/min/1.73m2
A total bilirubin, ALT, AST, and alkaline phosphatase of ≤ 2 ULN
Performance status of 0-2 based on the ECOG criteria. Patients with performance status 3 or 4, based solely on bone pain, are also eligible, provided that there is a source document to verify this
Prospective study participants must be informed of the investigational nature of the study and must have signed an IRB-approved informed consent form in accordance with institutional and federal guidelines
Exclusion Criteria:
Prior allogeneic transplant
Greater than grade 2 motor neuropathy or greater than grade 3 sensory neuropathy at screening
Uncontrolled diabetes
Recent (< 6 months) myocardial infarction, unstable angina, CABG or stent placement in the last 2 years, difficult-to-control congestive heart failure, uncontrolled hypertension (systolic blood pressure > 160 mm or a diastolic BP > 110 mm under normal conditions and while on appropriate anti-hypertensive medications), or difficult- to-control cardiac arrhythmias
Evidence of QT prolongation and/or torsades de pointes (TdP) on EKG.
Any co-morbid condition that poses a greater threat to the patient's life expectancy than the recurrent myeloma
No concurrent malignancy with a life expectancy of less than two years, or one that requires ongoing chemotherapeutic intervention at screening
Presence of an infection that requires intravenous antibiotics
Pregnant or nursing females. Any patient of reproductive potential may not participate unless he/she has agreed to use an effective contraceptive method as covered during the informed consent process
Known history of an HIV seropositive test
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guido Tricot, MD, PhD
Organizational Affiliation
University of Iowa
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
12. IPD Sharing Statement
Learn more about this trial
ATRA, Celecoxib, and Itraconazole as Maintenance
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