Randomized Trial of Cryotherapy Duration Prior to High Dose Melphalan in Myeloma Patients - Full Text View

Purpose

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	Intervention	Phase
Refractory Multiple Myeloma Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma	Procedure: cryotherapy Other: questionnaire administration Other: pharmacological study	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Multiple Myeloma

Drug Information available for: Melphalan Melphalan hydrochloride

Genetic and Rare Diseases Information Center resources: Multiple Myeloma

U.S. FDA Resources

Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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:

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 ] [ Designated as safety issue: No ]
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.


Estimated Enrollment:	140
Study Start Date:	April 2012
Estimated Primary Completion Date:	April 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01653106

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

Additional Information:

Jamesline

This link exits the ClinicalTrials.gov site

No publications provided


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
Study First Received:	July 26, 2012
Last Updated:	May 12, 2014
Health Authority:	United States: Institutional Review Board

Keywords provided by Ohio State University Comprehensive Cancer Center:


cryotherapy Melphalan Mucositis

Additional relevant MeSH terms:


Multiple Myeloma Neoplasms, Plasma Cell Blood Protein Disorders Cardiovascular Diseases Hematologic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Paraproteinemias	Vascular Diseases Melphalan Alkylating Agents Antineoplastic Agents Antineoplastic Agents, Alkylating Immunologic Factors Immunosuppressive Agents Molecular Mechanisms of Pharmacological Action Myeloablative Agonists Pharmacologic Actions Physiological Effects of Drugs Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015