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ATRA, Celecoxib, and Itraconazole as Maintenance

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ClinicalTrials.gov Identifier: NCT02401295
Recruitment Status : Completed
First Posted : March 27, 2015
Last Update Posted : February 23, 2017
Sponsor:
Information provided by (Responsible Party):
Guido Tricot, University of Iowa

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.

Condition or disease Intervention/treatment Phase
Relapsed Multiple Myeloma Drug: ATRA Drug: Celecoxib Drug: Itraconazole Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : May 2015
Actual Primary Completion Date : August 2015
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

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: ATRA
Other Names:
  • All-Trans-Retinoic Acid
  • tretinoin

Drug: Celecoxib
Other Name: Celebrex

Drug: Itraconazole
Other Names:
  • Sporanox
  • Onmel




Primary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety [ Time Frame: 6 months ]

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


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02401295


Locations
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United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
Sponsors and Collaborators
University of Iowa
Investigators
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Principal Investigator: Guido Tricot, MD, PhD University of Iowa

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Responsible Party: Guido Tricot, Principal Investigator, University of Iowa
ClinicalTrials.gov Identifier: NCT02401295     History of Changes
Other Study ID Numbers: 201311791
First Posted: March 27, 2015    Key Record Dates
Last Update Posted: February 23, 2017
Last Verified: February 2017
Keywords provided by Guido Tricot, University of Iowa:
Relapsed multiple myeloma
Additional relevant MeSH terms:
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Celecoxib
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Itraconazole
Hydroxyitraconazole
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents