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Randomized Trial of Cryotherapy Duration Prior to High Dose Melphalan in Myeloma Patients

Not Applicable
Completed
Conditions
Stage I Multiple Myeloma
Refractory Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Interventions
Procedure: cryotherapy
Other: questionnaire administration
Other: pharmacological study
Registration Number
NCT01653106
Lead Sponsor
Ohio State University Comprehensive Cancer Center
Brief Summary

The purpose of this study is to compare the effect of short-term (2 hours/120 minutes) and long-term (6 hours/360 minutes) schedules of crushed ice therapy (cryotherapy). Patients that receive high dose melphalan for bone marrow transplantation commonly develop significant mouth pain and sores (oral mucositis) unless cryotherapy is utilized. The goal of this study is to scientifically determine (using randomization and a larger sample size) if a short-term schedule is as effective as the standard long-term schedule in preventing, or minimizing the symptoms involved with oral mucositis. The study is also trying to determine the best dose of melphalan and how patient's body breaks down melphalan and will obtain blood through central venous catheter to measure the amount of melphalan in patient's blood at specific times after the melphalan is infused

Detailed Description

PRIMARY OBJECTIVES:

I. To measure the maximum inpatient mucositis grade after 120- vs. 360-minutes standardized cryotherapy regimens in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation at Ohio State Medical Center.

SECONDARY OBJECTIVES:

I. To develop a pharmacokinetic model predicting variability in unbound serum melphalan area under the concentration-time curve (AUC).

II. To compare the neutropenic fever and bacteremia incidence after 120- vs. 360-minute cryotherapy regimens.

III. To compare patient-reported mucositis-related symptoms up until discharge utilizing the Patient-Reported Oral Mucositis Symptoms Scale (PROMS) after 120- vs 360-minute cryotherapy regimens.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Beginning fifteen minutes before melphalan treatment, patients receive 1 ounce of shaved ice in their mouth, allow it to melt and then replenish it immediately for 120 minutes.

ARM II: Beginning fifteen minutes before melphalan treatment, patients receive 1 ounce of shaved ice in their mouth, allow it to melt and then replenish it immediately for 360 minutes.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
148
Inclusion Criteria
  • Patients must be diagnosed with multiple myeloma be admitted for autologous stem cell transplantation
  • Age > 18 years
  • Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial
Exclusion Criteria
  • Any other medical condition, including mental illness or substance abuse, deemed by the principal investigator to likely interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm I (cryotherapy 120 minutes)pharmacological studyBeginning fifteen minutes before melphalan treatment, patients receive 1 ounce of shaved ice in their mouth, allow it to melt and then replenish it immediately for 120 minutes.
Arm I (cryotherapy 120 minutes)cryotherapyBeginning fifteen minutes before melphalan treatment, patients receive 1 ounce of shaved ice in their mouth, allow it to melt and then replenish it immediately for 120 minutes.
Arm I (cryotherapy 120 minutes)questionnaire administrationBeginning fifteen minutes before melphalan treatment, patients receive 1 ounce of shaved ice in their mouth, allow it to melt and then replenish it immediately for 120 minutes.
Arm II (cryotherapy 360 minutes)cryotherapyBeginning fifteen minutes before melphalan treatment, patients receive 1 ounce of shaved ice in their mouth, allow it to melt and then replenish it immediately for 360 minutes.
Arm II (cryotherapy 360 minutes)questionnaire administrationBeginning fifteen minutes before melphalan treatment, patients receive 1 ounce of shaved ice in their mouth, allow it to melt and then replenish it immediately for 360 minutes.
Arm II (cryotherapy 360 minutes)pharmacological studyBeginning fifteen minutes before melphalan treatment, patients receive 1 ounce of shaved ice in their mouth, allow it to melt and then replenish it immediately for 360 minutes.
Primary Outcome Measures
NameTimeMethod
Incidence of severe (Grade 3 or 4) mucositis achieved between two different cryotherapy regimens during inpatient hospitalization based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 421 days

A Cochran-Mantel-Haenszel chi-square test will be used to compare the proportion of patients who develop severe mucositis between those treated with 120-minute vs. 360-minute cryotherapy. Logistic regression modeling will also be used with incidence of severe mucositis as the dependent variable and assess various factors in addition to treatment arm on this incidence.

Secondary Outcome Measures
NameTimeMethod
Melphalan pharmacokinetic model including apparent volume of the central compartment (Vc), elimination rate of constant (Ke), half-life (t1/2), systemic clearance (CLs), and AUC.Pre-dose, within 5 minutes prior to completion of infusion, at 5, 15, 30, 45, and 60 minutes, and 3 and 6 hours post end of infusion

All pharmacokinetic results will be summarized using appropriate descriptive statistics. A nonlinear mixed effects approach will be used for modeling melphalan pharmacokinetics, identifying significant covariates, and relating these to mucositis.

Trial Locations

Locations (1)

Ohio State University Medical Center

🇺🇸

Columbus, Ohio, United States

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