ATRA, Celecoxib, and Itraconazole as Maintenance

February 20, 2017 updated by: Guido Tricot, University of Iowa

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • 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
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics

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

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ATRA/celecoxib/itraconazole

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.
Drug: Itraconazole
Other Names:
  • Sporanox
  • Onmel
Drug: Celecoxib
Other Names:
  • Celebrex
Drug: ATRA
Other Names:
  • tretinoin
  • All-Trans-Retinoic Acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of Participants with Adverse Events as a Measure of Safety
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Blood and Bone Marrow Aspirate Samples as a measure of changes to the MMSC (multiple myeloma stem cell) fraction.
Time Frame: 6 months
6 months

Collaborators and Investigators

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

Sponsor

University of Iowa

Investigators

  • Principal Investigator: Guido Tricot, MD, PhD, University of Iowa

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

May 1, 2015

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

November 1, 2016

Study Registration Dates

First Submitted

March 18, 2015

First Submitted That Met QC Criteria

March 23, 2015

First Posted (Estimate)

March 27, 2015

Study Record Updates

Last Update Posted (Actual)

February 23, 2017

Last Update Submitted That Met QC Criteria

February 20, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201311791

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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