Treatment of Breast Cancer-related Lymphedema With Stem Cells and Fat Grafting

Breast cancer-related lymphedema is one of the most common and feared consequences of breast cancer treatment. Currently, lymphedema is primarily addressed conservatively with compression garments. Regenerative medicine may provide a new treatment option for lymphedema. This Phase 3 trial will examine the efficacy, effectiveness and safety of freshly isolated adipose-derived stromal cells administered in conjunction with a fat grafting procedure to the affected axillary region.

Study Overview

• Status: Completed
• Conditions: Lymphedema
• Intervention / Treatment: Procedure: Liposuction; Procedure: Fat graft; Biological: Stem cell injection; Procedure: Sham graf (Saline injection); Procedure: Saline injection

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Department of plastic and reconstructive Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Unilateral arm lymphedema secondary to breast cancer treatment including lymph node dissection.
• Cancer free for at least 1 year
• The patient understands the nature and purpose of this study and the study procedures and has signed informed consent.
• The opposite upper extremity is healthy (no lymphedema).
• ASA score of 1 or 2.
• The patient is able to read, understand, and complete Danish questionnaires.
• Pitting lymphedema ISL grade 1 or 2.
• A minimum circumference difference of 2cm or a minimum volume difference of 200mL.

Exclusion Criteria:

• Pregnant or lactating.
• Bilateral lymphedema
• Current or previous malignancies other than breast cancer.
• Insulin-dependent diabetes.
• Diagnosed with any form of psychotic disorder, which may impact study participation.
• Not ceased smoking during treatment.
• Active implantables (e.g. pacemaker or neurostimulator)
• Unrealistic treatment expectations.
• Known hepatitis, HIV or syphilis infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Active treatment	Procedure: Liposuction; Liposuction is performed on the abdomen or thighs.; Procedure: Fat graft; 30mL harvested lipoaspirate is injected at the affected axillary site.; Other Names: lipotransfer; Biological: Stem cell injection; 4mL stem cell suspension injected at the affected axillary site.
PLACEBO_COMPARATOR: Placebo treatment	Procedure: Liposuction; Liposuction is performed on the abdomen or thighs.; Procedure: Sham graf (Saline injection); 30mL saline is injected at the affected axillary site.; Procedure: Saline injection; 4mL saline injected at the affected axillary site.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in arm volume	Assessed using clinical circumference measurement	Baseline, 3, 6, 9 and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of treatments: Assessed by asking the patient at each visit	Any side effects to treatments. Assessed by asking the patient at each visit.	Baseline, 3, 6, 9 and 12 months
Subjective changes assessed using the LYMPH-ICF (Lymphoedema Functioning, Disability and Health) questionaire	Subjective change of lymphedema assessed by questionnaire. Range: 0-100. 100 being the most bothered.	Baseline, 3, 6, 9 and 12 months
Subjective changes assessed using DASH (DISABILITIES OF THE ARM, SHOULDER AND HAND) questionaire	Subjective change of lymphedema assessed by questionnaire. Range: 1-5. 5 being the most bothered	Baseline, 3, 6, 9 and 12 months
Subjective changes assessed using SF-36 questionnaire	Subjective change of quality of life assessed by questionnaire. Range: 0-100. 0 being the most bothered.	Baseline, 3, 6, 9 and 12 months
Change in lymph drainage	Change in lymph drainage assessed by indocyanine-green lymphangiography	Baseline and 12 months
Change in conservative lymphedema treatment	Change in use or type of conservative lymphedema treatments	Baseline, 3, 6, 9 and 12 months
Change in adverse lymphedema-related events	Change in infection rates and sick-days due to lymphedema.	Baseline, 3, 6, 9 and 12 months
Change in L-DEX score (bioimpedance)	Change in L-DEX score of lymphedema arm derived from bioimpedance. Higher values mean more fluid in the lymphedema arm compared to the healthy arm.	Baseline, 3, 6, 9 and 12 months
Change in weight and arm tissue composition	Assessed using dual energy x-ray absorptiometry (DXA) scan. Change in values from baseline.	Baseline, 3, 6, 9 and 12 months

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Investigators: Study Chair: Jens A Sørensen, MD, PhD, Department of Plastic Surgery, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 18, 2018
• Primary Completion (ACTUAL): June 1, 2021
• Study Completion (ACTUAL): June 1, 2021

Study Registration Dates

• First Submitted: November 12, 2018
• First Submitted That Met QC Criteria: December 14, 2018
• First Posted (ACTUAL): December 17, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 25, 2021
• Last Update Submitted That Met QC Criteria: June 24, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Lymphatic Diseases; Postoperative Complications; Lymphedema; Breast Cancer Lymphedema
• Other Study ID Numbers: S-20180117

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No