ATRA, Celecoxib, and Itraconazole as Maintenance

NCT02401295 | Completed Phase 1 DMC

• 1 other identifier: 201311791
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Relapsed Multiple Myeloma

Keywords

Relapsed multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety

  6 months

Secondary Outcomes (1)

• Blood and Bone Marrow Aspirate Samples as a measure of changes to the MMSC (multiple myeloma stem cell) fraction.

  6 months

Study Arms (1)

ATRA/celecoxib/itraconazole

EXPERIMENTAL

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; Drug: Celecoxib; Drug: Itraconazole

Interventions

ATRA DRUG

Also known as: All-Trans-Retinoic Acid, tretinoin

ATRA/celecoxib/itraconazole

Celecoxib DRUG

Also known as: Celebrex

ATRA/celecoxib/itraconazole

Itraconazole DRUG

Also known as: Sporanox, Onmel

ATRA/celecoxib/itraconazole

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of relapsed multiple myeloma
• Recent salvage transplant (≤ 6 months but ≥ 45 days post-transplant prior to study enrollment) for relapse
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Iowa: lead

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Tretinoin; Celecoxib; Itraconazole

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Triazoles; Piperazines

Study Officials

• Guido Tricot, MD, PhD

  University of Iowa

  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: March 18, 2015
• First Posted: March 27, 2015
• Study Start: May 1, 2015
• Primary Completion: August 1, 2015
• Study Completion: November 1, 2016
• Last Updated: February 23, 2017

Record last verified: 2017-02

Locations

US (1)