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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Condition or disease	Intervention/treatment	Phase
Refractory Multiple Myeloma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma	Procedure: cryotherapy; Other: questionnaire administration; Other: pharmacological study	Not Applicable

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	148 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Randomized Study to Compare the Effect of Short- and Long-Term Schedules of Cryotherapy on the Incidence and Severity of Mucositis in High-Dose Melphalan
Actual Study Start Date :	April 2012
Actual Primary Completion Date :	May 2014
Actual Study Completion Date :	March 2015

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Arm I (cryotherapy 120 minutes); 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.	Procedure: cryotherapy; Receive shaved ice Other: questionnaire administration; Participate in PROMS Other: pharmacological study; Correlative studies; Other Name: pharmacological studies
Active Comparator: Arm II (cryotherapy 360 minutes); 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.	Procedure: cryotherapy; Receive shaved ice Other: questionnaire administration; Participate in PROMS Other: pharmacological study; Correlative studies; Other Name: pharmacological studies

Outcome Measures

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Primary Outcome Measures :

1. 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 4 [ Time Frame: 21 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 :

1. 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. [ Time Frame: 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210

Sponsors and Collaborators

Ohio State University Comprehensive Cancer Center

Investigators

Principal Investigator:	Craig Hofmeister, MD	Ohio State University

More Information

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Additional Information:

Jamesline 

Responsible Party:	Craig Hofmeister, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT01653106 History of Changes
Other Study ID Numbers:	OSU-11055; NCI-2012-00459 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted:	July 30, 2012
Last Update Posted:	June 27, 2017
Last Verified:	June 2017

Keywords provided by Craig Hofmeister, Ohio State University Comprehensive Cancer Center:

cryotherapy; Melphalan; Mucositis

Additional relevant MeSH terms:

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; Melphalan; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs