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Clinical Study With Lymfactin® in the Treatment of Patients With Secondary Lymphedema (AdeLE) (AdeLE)

Primary Purpose

Secondary Lymphedema

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Lymfactin® (1x10E11 vp)
Placebo
Sponsored by
Herantis Pharma Plc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Secondary Lymphedema focused on measuring Lymphedema, Breast cancer, Adenoviral vector, VEGF-C

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Female or male patients with secondary lymphedema associated with the treatment of breast cancer and

    • Has undergone sentinel lymph node biopsies and/or lymph node resection in the axilla on the affected side of their breast cancer with initial N1-N2a staging and lymph node metastasis in ≤ 9 axillary lymph nodes.
    • Requires garment use as a compression treatment for the lymphedema in the affected arm.
    • Has the volume of the affected arm at least 10% greater than the unaffected arm following 7 days without compression garment.
    • Has the presence of pitting edema in the affected arm without compression garment.
    • Has had lymphedema for less than 5 years.
  2. No evidence of recurrent or active breast cancer for at least 2 years after the breast cancer surgery and/or the end of chemotherapy and/or radiotherapy (excluding endocrine treatment).
  3. Patient understands and voluntarily signs the written informed consent prior to any screening procedure.
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  5. Body Mass Index (BMI) between 18 and 32 inclusive.
  6. Positron Emission Tomography-Computed Tomography (PET CT) scan of the chest and the abdomen within 45 days before the study treatment without signs of active breast cancer or any other malignancy.
  7. Adequate hematologic and end-organ function.

    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x the institutional upper limit of normal (ULN)
    • Bilirubin ≤ 1.5 x ULN (except in patients with previously documented Gilbert's syndrome, in which case total bilirubin ≤ 3 x ULN)
    • International Normalized ratio (INR) and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN (for patients requiring therapeutic anticoagulation therapy, a stable INR ≤ 2,5)
    • Serum creatinine ≤ 1,5 x ULN or creatinine clearance ≥ 50 ml/min
    • Absolute neutrophil count (ANC) ≥ 1,5 E9/l
    • Platelet count ≥ 100 E9/l
    • Hemoglobin ≥ 100 g/l
  8. Willingness to comply with scheduled visits, laboratory assessments, and other study-related procedures due to the regulatory requirements related to gene based therapies.
  9. Non-smoker or willing to stop smoking or use of nicotine-containing products for at least 4 weeks prior to the study entry.
  10. Negative urine pregnancy test (only patients with childbearing potential) at screening and use of adequate contraceptive measures from screening until six months after the study treatment administration:

    • A patient with childbearing potential should be using a reliable contraception method: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal, progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device (IUD), intrauterine hormone releasing system (IUS), bilateral tubal occlusion, vasectomised partner or sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments.
    • A male patient is not allowed to donate sperm.
    • A patient with no current heterosexual relationship may be included according to the judgement of the Investigator.
    • For patient in postmenopausal state neither contraception nor a pregnancy test is required. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy.
    • For permanently sterile patient neither contraception nor a pregnancy test is required. A permanently sterile is defined by history of hysterectomy, bilateral salpingectomy or bilateral oophorectomy.

Exclusion Criteria:

  1. Diagnosed for T4 and/or N2b/N3 stage breast cancer at the time of the original diagnosis.
  2. Evidence (clinical, laboratory or imaging) or history of a neoplasm other than breast cancer (except basal cell carcinoma or cervical in situ carcinoma).
  3. Diagnosed for metastatic breast cancer.
  4. Pregnancy, lactation or a positive or indeterminate pregnancy test.
  5. Current treatment with Cyclooxygenase-2 (COX-2) inhibitors should be interrupted from 2 weeks prior until 4 weeks post-treatment.
  6. Previous treatment with, or participation in a trial of a gene therapy product.
  7. Participation in a clinical trial, which has included interventions in the preceding 6 months or will involve future interventions. Participation in a non-interventional clinical trial, or in a non-interventional follow-up of any clinical trial, does not make the patient inappropriate for the entry into this study.
  8. Current treatment with immunosuppressive drugs.
  9. Current history of drug abuse, including nicotine-containing products, or alcohol abuse.
  10. Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness.
  11. History of hepatic dysfunction, cirrhosis, or hepatitis.
  12. Allergy to any ingredients of the Lymfactin® solution for injection.
  13. Other concurrent severe acute and/or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with the study participation or study drug administration, that would, in the Investigator's judgement, affect the patient's ability to follow study-related procedures, or that may interfere with the interpretation of study results and would make the patient inappropriate for the entry into this study.
  14. Doubtful availability, in the opinion of the Investigator, to complete the study.

Sites / Locations

  • Töölö Hospital, Department of Plastic Surgery
  • Tampere University Hospital, Department of Plastic Surgery
  • Turku University Hospital, Department of Plastic Surgery
  • Karolinska University Hospital, Department of Reconstructive Plastic Surgery
  • Uppsala University Hospital, Department of Plastic Surgery

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Lymfactin® (1x10E11 vp)

Placebo (0.9% physiological saline)

Arm Description

Lymfactin® will be administered as a single dose via perinodal injection in a volume of 2 mL.

Placebo will be administered as a single dose via perinodal injection in a volume of 2 mL.

Outcomes

Primary Outcome Measures

Measurement of the volume of the arms
Changes in the volume of the affected arm and comparison to the unaffected arm.
Measurement of the lymphatic flow of the affected arm by quantitative lymphoscintigraphy (99Tc-nanocolloid clearance rate with calculation of transport index).
Assessment of the changes in the lymphatic flow.
Questionnaire according to the Lymphedema Quality of Life Inventory (LQOLI)
Assessment of changes in the quality of life using Lymphedema Quality of Life Inventory (LQOLI) in which the patients assess how their lymphedema is affecting the activities of daily living. LQOLI consists of three dimensions: Physical, psychosocial and practical, which are reported separately as the mean score of that part. Each part of the LQOLI is scored from 0 to 3, where score 0 means "no impact", 1 means "a little bit impact", 2 means "somewhat impact" and score 3 means "significant impact" on the quality of life of the patient, the smaller score thus being the better.

Secondary Outcome Measures

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Adverse Events as assessed by CTCAE v4.0 to evaluate the safety profile after administration of Lymfactin.
CT scan of chest and abdomen
Changes in CT scans of chest and abdomen in order to detect malignancies.
Lymfactin genome copy number in blood
Changes in Lymfactin genome copy number in blood.
Lymfactin genome copy number in wound secretion
Changes in Lymfactin genome copy number in wound secretion.
Formation of anti-Lymfactin antibodies
Changes in anti-Lymfactin antibody titer in blood.
Systemic concentration of vascular endothelial growth factor C (VEGF-C)
Changes in the VEGF-C concentration in blood.

Full Information

First Posted
July 6, 2018
Last Updated
October 18, 2023
Sponsor
Herantis Pharma Plc.
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1. Study Identification

Unique Protocol Identification Number
NCT03658967
Brief Title
Clinical Study With Lymfactin® in the Treatment of Patients With Secondary Lymphedema (AdeLE)
Acronym
AdeLE
Official Title
Phase 2, Double-Blind, Placebo-Controlled, Randomized Efficacy, Safety and Tolerability Study of Lymfactin in Combination With Surgical Lymph Node Transfer To Patients With Secondary Lymphedema Associated With the Treatment of Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 7, 2018 (Actual)
Primary Completion Date
December 16, 2019 (Actual)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Herantis Pharma Plc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study evaluates the efficacy of Lymfactin® in patients with secondary lymphedema associated with the treatment of breast cancer by comparing the effects of active study treatment Lymfactin® to placebo. The study product will be administered in combination with a surgical lymph node transfer operation. In addition, the safety and tolerability of the Lymfactin® treatment will be evaluated.
Detailed Description
This is a Phase II, double-blind, placebo-controlled, multi-centre clinical study, in which 40 patients with breast cancer associated secondary lymphedema will be randomized 1:1 either to Lymfactin® (1 x 10E11 viral particles, vp) or placebo (0.9% physiological saline) group. The study product (Lymfactin® or placebo solution) will be administered as a single dose in a volume of two (2) mL, by ex vivo perinodal injection into the fat pad of a flap of tissue containing lymph nodes from the patient's own abdominal wall or the groin area. This flap of tissue will then be surgically implanted into the axillary region of the affected arm. This treatment with the study product is performed in combination with a surgical lymph node transfer, in conjunction with or without breast reconstruction surgery. Patients will be followed-up for efficacy and safety according to a specified schedule up to 5 years post-treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Secondary Lymphedema
Keywords
Lymphedema, Breast cancer, Adenoviral vector, VEGF-C

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Double-blind, placebo-controlled, randomized
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blind
Allocation
Randomized
Enrollment
39 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lymfactin® (1x10E11 vp)
Arm Type
Active Comparator
Arm Description
Lymfactin® will be administered as a single dose via perinodal injection in a volume of 2 mL.
Arm Title
Placebo (0.9% physiological saline)
Arm Type
Placebo Comparator
Arm Description
Placebo will be administered as a single dose via perinodal injection in a volume of 2 mL.
Intervention Type
Drug
Intervention Name(s)
Lymfactin® (1x10E11 vp)
Other Intervention Name(s)
LX-1101, AdAptVEGF-C adenoviral vector
Intervention Description
Lymfactin® will be administered as a single dose via perinodal injection in a volume of 2 mL.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
0.9% Physiological saline
Intervention Description
Placebo will be administered as a single dose via perinodal injection in a volume of 2 mL.
Primary Outcome Measure Information:
Title
Measurement of the volume of the arms
Description
Changes in the volume of the affected arm and comparison to the unaffected arm.
Time Frame
24 Months
Title
Measurement of the lymphatic flow of the affected arm by quantitative lymphoscintigraphy (99Tc-nanocolloid clearance rate with calculation of transport index).
Description
Assessment of the changes in the lymphatic flow.
Time Frame
24 Months
Title
Questionnaire according to the Lymphedema Quality of Life Inventory (LQOLI)
Description
Assessment of changes in the quality of life using Lymphedema Quality of Life Inventory (LQOLI) in which the patients assess how their lymphedema is affecting the activities of daily living. LQOLI consists of three dimensions: Physical, psychosocial and practical, which are reported separately as the mean score of that part. Each part of the LQOLI is scored from 0 to 3, where score 0 means "no impact", 1 means "a little bit impact", 2 means "somewhat impact" and score 3 means "significant impact" on the quality of life of the patient, the smaller score thus being the better.
Time Frame
24 Months
Secondary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
Adverse Events as assessed by CTCAE v4.0 to evaluate the safety profile after administration of Lymfactin.
Time Frame
24 Months
Title
CT scan of chest and abdomen
Description
Changes in CT scans of chest and abdomen in order to detect malignancies.
Time Frame
60 Months
Title
Lymfactin genome copy number in blood
Description
Changes in Lymfactin genome copy number in blood.
Time Frame
30 Days
Title
Lymfactin genome copy number in wound secretion
Description
Changes in Lymfactin genome copy number in wound secretion.
Time Frame
7 Days
Title
Formation of anti-Lymfactin antibodies
Description
Changes in anti-Lymfactin antibody titer in blood.
Time Frame
12 Months
Title
Systemic concentration of vascular endothelial growth factor C (VEGF-C)
Description
Changes in the VEGF-C concentration in blood.
Time Frame
30 Days
Other Pre-specified Outcome Measures:
Title
Optional evaluation of the anatomy and functionality of lymphatic vessels by MRI lymphangiography
Description
Changes in anatomy and functionality of lymphatic vessels by newly developed MRI lymphangiography and comparison of the correlation of the method to the already established lymphoscintigraphy in the assessment of lymphedema.
Time Frame
24 Months
Title
Percentage Water Content (PWC) measurement of water content and edema
Description
Changes in PWC measurement of water content and edema in affected arm and comparison to the unaffected arm.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female or male patients with secondary lymphedema associated with the treatment of breast cancer and Has undergone sentinel lymph node biopsies and/or lymph node resection in the axilla on the affected side of their breast cancer with initial N1-N2a staging and lymph node metastasis in ≤ 9 axillary lymph nodes. Requires garment use as a compression treatment for the lymphedema in the affected arm. Has the volume of the affected arm at least 10% greater than the unaffected arm following 7 days without compression garment. Has the presence of pitting edema in the affected arm without compression garment. Has had lymphedema for less than 5 years. No evidence of recurrent or active breast cancer for at least 2 years after the breast cancer surgery and/or the end of chemotherapy and/or radiotherapy (excluding endocrine treatment). Patient understands and voluntarily signs the written informed consent prior to any screening procedure. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Body Mass Index (BMI) between 18 and 32 inclusive. Positron Emission Tomography-Computed Tomography (PET CT) scan of the chest and the abdomen within 45 days before the study treatment without signs of active breast cancer or any other malignancy. Adequate hematologic and end-organ function. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x the institutional upper limit of normal (ULN) Bilirubin ≤ 1.5 x ULN (except in patients with previously documented Gilbert's syndrome, in which case total bilirubin ≤ 3 x ULN) International Normalized ratio (INR) and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN (for patients requiring therapeutic anticoagulation therapy, a stable INR ≤ 2,5) Serum creatinine ≤ 1,5 x ULN or creatinine clearance ≥ 50 ml/min Absolute neutrophil count (ANC) ≥ 1,5 E9/l Platelet count ≥ 100 E9/l Hemoglobin ≥ 100 g/l Willingness to comply with scheduled visits, laboratory assessments, and other study-related procedures due to the regulatory requirements related to gene based therapies. Non-smoker or willing to stop smoking or use of nicotine-containing products for at least 4 weeks prior to the study entry. Negative urine pregnancy test (only patients with childbearing potential) at screening and use of adequate contraceptive measures from screening until six months after the study treatment administration: A patient with childbearing potential should be using a reliable contraception method: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal, progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device (IUD), intrauterine hormone releasing system (IUS), bilateral tubal occlusion, vasectomised partner or sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. A male patient is not allowed to donate sperm. A patient with no current heterosexual relationship may be included according to the judgement of the Investigator. For patient in postmenopausal state neither contraception nor a pregnancy test is required. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. For permanently sterile patient neither contraception nor a pregnancy test is required. A permanently sterile is defined by history of hysterectomy, bilateral salpingectomy or bilateral oophorectomy. Exclusion Criteria: Diagnosed for T4 and/or N2b/N3 stage breast cancer at the time of the original diagnosis. Evidence (clinical, laboratory or imaging) or history of a neoplasm other than breast cancer (except basal cell carcinoma or cervical in situ carcinoma). Diagnosed for metastatic breast cancer. Pregnancy, lactation or a positive or indeterminate pregnancy test. Current treatment with Cyclooxygenase-2 (COX-2) inhibitors should be interrupted from 2 weeks prior until 4 weeks post-treatment. Previous treatment with, or participation in a trial of a gene therapy product. Participation in a clinical trial, which has included interventions in the preceding 6 months or will involve future interventions. Participation in a non-interventional clinical trial, or in a non-interventional follow-up of any clinical trial, does not make the patient inappropriate for the entry into this study. Current treatment with immunosuppressive drugs. Current history of drug abuse, including nicotine-containing products, or alcohol abuse. Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness. History of hepatic dysfunction, cirrhosis, or hepatitis. Allergy to any ingredients of the Lymfactin® solution for injection. Other concurrent severe acute and/or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with the study participation or study drug administration, that would, in the Investigator's judgement, affect the patient's ability to follow study-related procedures, or that may interfere with the interpretation of study results and would make the patient inappropriate for the entry into this study. Doubtful availability, in the opinion of the Investigator, to complete the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Saarikko, MD, PhD
Organizational Affiliation
Helsinki University Central Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Maria Mani, MD, PhD
Organizational Affiliation
Uppsala University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Töölö Hospital, Department of Plastic Surgery
City
Helsinki
Country
Finland
Facility Name
Tampere University Hospital, Department of Plastic Surgery
City
Tampere
Country
Finland
Facility Name
Turku University Hospital, Department of Plastic Surgery
City
Turku
Country
Finland
Facility Name
Karolinska University Hospital, Department of Reconstructive Plastic Surgery
City
Stockholm
Country
Sweden
Facility Name
Uppsala University Hospital, Department of Plastic Surgery
City
Uppsala
Country
Sweden

12. IPD Sharing Statement

Learn more about this trial

Clinical Study With Lymfactin® in the Treatment of Patients With Secondary Lymphedema (AdeLE)

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