Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000732583p
Ethics application status
Submitted, not yet approved
Date submitted
11/05/2024
Date registered
14/06/2024
Date last updated
14/06/2024
Date data sharing statement initially provided
14/06/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety, Feasibility, and Dose Study of Aethlon Hemopurifier in Solid Tumor Patients on Pembrolizumab or Nivolumab Monotherapy.
Scientific title
Safety, Feasibility, and Dose-Finding Study of Aethlon Hemopurifier in
Patients with Solid Tumors who have stable or progressive disease
during Pembrolizumab or Nivolumab Monotherapy
Secondary ID [1] 311752 0
AEMD 2022-06
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 333248 0
Condition category
Condition code
Cancer 329937 329937 0 0
Lung - Non small cell
Cancer 329938 329938 0 0
Malignant melanoma
Cancer 329939 329939 0 0
Bladder
Cancer 329940 329940 0 0
Kidney
Cancer 329941 329941 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 329942 329942 0 0
Head and neck
Cancer 329943 329943 0 0
Stomach
Cancer 329944 329944 0 0
Cervical (cervix)
Cancer 329945 329945 0 0
Lung - Mesothelioma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Hemopurifier (HP) is a single-use hollow-fiber plasmapheresis cartridge that is modified to contain an Affinity Resin in the plasma space along the length of the hollow fibers. The Affinity Resin has broad-spectrum avidity for exosomes. As blood enters the HP, exosomes in the plasma are transported via convection and diffusion through pores in the hollow fibers having nominal pore sizes of 200 nm where they contact the affinity matrix. The exosomes are captured by the Affinity Resin and prevented from re-entry into the circulation. Meanwhile, the cellular components of the blood remain within the lumen of the fibers and are excluded from contact with the affinity resin The Hemopurifier treatment will last for 4 hours.

During the Hemopurifier treatment, anticoagulation therapy, such as heparin, will be administered to guaranty a systemic anticoagulation

The HP is operated via established central access to a patient’s circulatory system and utilizing standard dialysis machines as blood pumps. A central venous dialysis catheter will be placed prior to treatment. The placement of the catheter will be performed by appropriately credentialed physicians using well-established, standardized sterile procedures.

Participant will be assigned to a distinct cohort employing a 3+3 design with each patient serving as his or her. Each First 3 patients own control, each cohort will be comprised of 3 patients; enrollment will proceed as follows:
If no patients in a given cohort experience a dose limiting toxicities (DLT) in the 7 days followup after the last HP treatment, enrollment in the subsequent cohort will begin (first group will start in cohort 1).
If 1 patient in a cohort experiences a DLT, 3 additional patients will be enrolled in that cohort; if greater than or equal to 1 of the additional 3 patients in this group experiences a DLT, enrollment will be stopped. Otherwise, enrollment in the subsequent cohort will begin.
If greater than or equal to 2 patients in a given cohort experience a DLT, enrollment in the trial will be stopped.


if in cohort 1, patient will receive one, 4-hour long treatment only and will receive pembrolizumab or nivolumab right after. (within +3 day if needed).
If in cohort 2, patient will receive two, 4-hour long treatment (e.g Monday and Friday) and he will receive pembrolizumab or nivolumab right after the last session( (within +3 day if needed)
If in cohort 3, patient will receive three, 4-hour long treatment (e.g Monday, Wednesday, Friday) and he will receive pembrolizumab or nivolumab right after the last session (within +3 day if needed).


Following the HP Period, patients will continue to receive pembrolizumab (every 3 weeks) or nivolumab (every 2 weeks) throughout the Follow-up Period
(52 weeks following the HP Period). The duration of anti-PD-1 therapy during the Follow-up Period is at the discretion of the treating physician.
Intervention code [1] 328208 0
Treatment: Devices
Comparator / control treatment
The Hemopurifier period will employ a 3+3 design with each patient serving as his or her own control.
Each cohort will comprise 3 patients; cohort enrollment will proceed as follows:

If no patients in a given cohort experience a dose limiting toxicities (DLTs) in the 7 day follow-up after the last HP treatment, enrollment in the subsequent cohort will begin.

If 1 patient in a cohort experiences a DLT, 3 additional patients will be enrolled in that cohort; if greater than or equal to 1 of the 3 additional patients in this group experiences a DLT, enrollment will be stopped. Otherwise, enrollment in the subsequent cohort will begin.

If greater than or equal to 2 patients in a given cohort experience a DLT, enrollment in the trial will be stopped.

In the Run-in period (control period) patients will undergo a 60-days of of pembrolizumab or nivolumab therapy; The dose and schedule of pembrolizumab or nivolumab will be at the investigator’s discretion.

Hemopurifier period patients will undergo 4-hour Hemopurifier (HP) sessions prior to receiving anti-PD-1 therapy, and the HP treatments will be performed at different intervals depending on the cohort.
Control group
Active

Outcomes
Primary outcome [1] 337698 0
Safety and tolerability assessed by dose-limiting toxicities, treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs) and unanticipated serious adverse device effects (USADEs),
Timepoint [1] 337698 0
Assessed daily for the first 7 days following the HP period/treatment
Primary outcome [2] 338288 0
Treatment-emergent adverse events (TEAEs).
Timepoint [2] 338288 0
Assessed daily for the first 7 days following the HP period/treatment.
Primary outcome [3] 338293 0
Treatment-emergent serious adverse events (SAEs)
Timepoint [3] 338293 0
All SAEs are assessed from the time of informed consent until 30 days following the last HP
treatment
Secondary outcome [1] 432897 0
Change in total exosomal concentration
Timepoint [1] 432897 0
1) Run-in Period: Blood samples for the exosomal concentration study will be collected at days 0, day 28 and day 59.
2) Hemopurifier treatment period: Blood samples for the exosomal concentration study will be collected prior to first HP treatment (Day -4 for Cohorts 2 and 3; Day 0 for Cohort 1)
3) HP Period: Blood samples for the exosomal concentration study will be collected every 2 hours during HP treatment (Days -4, -2 and 0 for Cohort 2; Days -4, -3, -2, -1 and 0 for Cohort 3; Day 0 for Cohort 1)
4) Follow-up Period: Blood samples for the exosomal concentration study will be collected ones at weeks 1, 2, 3, 4 and week 8 after the last HP treatment for all cohorts.
Secondary outcome [2] 435488 0
Change in exosomal cargo overtime
Timepoint [2] 435488 0
1) Run-in Period: Blood samples for the exosomal cargo study will be collected at days 0, day 28 and day 59.
2) Hemopurifier treatment period: Blood samples for the exosomal cargo study will be collected prior to first HP treatment (Day -4 for Cohorts 2 and 3; Day 0 for Cohort 1)
3) HP Period: Blood samples for the exosomal studies will be collected every 2 hours during HP treatment (Days -4, -2 and 0 for Cohort 2; Days -4, -3, -2, -1 and 0 for Cohort 3; Day 0 for Cohort 1)
4) Follow-up Period: Blood samples for the exosomal cargo study will be collected ones at weeks 1, 2, 3, 4 and week 8 after the last HP treatment for all cohorts.
Secondary outcome [3] 435489 0
Change in exosomal subsets overtime
Timepoint [3] 435489 0
1) Run-in Period: Blood samples for the exosomal subset study will be collected at days 0, day 28 and day 59.
2) Hemopurifier treatment period: Blood samples for the exosomal subset study will be collected prior to first HP treatment (Day -4 for Cohorts 2 and 3; Day 0 for Cohort 1)
3) HP Period: Blood samples for the exosomal studies will be collected every 2 hours during HP treatment (Days -4, -2 and 0 for Cohort 2; Days -4, -3, -2, -1 and 0 for Cohort 3; Day 0 for Cohort 1)
4) Follow-up Period: Blood samples for the exosomal subset study will be collected ones at weeks 1, 2, 3, 4 and week 8 after the last HP treatment for all cohorts.

Eligibility
Key inclusion criteria
Histologic diagnosis of one of the following solid tumors:
Non-small cell lung cancer
Melanoma
Bladder/urinary tract cancer (urothelial cancer)
Renal cancer
Colorectal cancer (microsatellite instability-high (msi-h)
or a mismatch repair deficient (dmmr) solid tumor)
Gastric or gastroesophageal junction or esophageal cancer
Head and neck cancer
Cervical cancer
Mesothelioma

2. Patient is going to receive treatment with pembrolizumab or nivolumab
monotherapy or has been receiving this treatment for less than or equal to 2 weeks.
3. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1
Measurable disease by RECIST 1.1.
5. greater than or equal to 18 years of age.
6. Ability to provide informed consent.
7. Life expectancy of at least 12 weeks.
8. Women of childbearing potential (WOCBP) and men must agree to use
adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry and through 120 days after the HP
treatment. Should a woman become pregnant or suspect she is pregnant
while she or her partner is participating in this study, the treating physician
should be informed immediately. Men treated or enrolled on this protocol
must also agree to use adequate contraception prior to the study and for the
duration of study participation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of brain or leptomeningeal metastasis.
2. Immunodeficiency disorder.
3. Use of more than 10 mg/day of prednisone or equivalent in the 30 days
leading up to enrollment.
4. Any autoimmune condition requiring treatment in the year prior to
enrollment.
5. Currently being treated for acute non-infectious pneumonitis.
6. Pregnant or breastfeeding (WOCBP must have a negative urine pregnancy
test on the day but prior to the first HP treatment).
7. HIV infection.
8. Active hepatitis B or C infection.
9. Use of an angiotensin-converting enzyme (ACE) inhibitor within 14 days
prior to a HP treatment.
10. Systolic blood pressure <100 mmHg during Screening Period in a patient
with a history of a systolic blood pressure greater than or equal to 100 mmHg.
11. Contraindication to anticoagulation:
-->Unable to tolerate full therapeutic anticoagulation therapy for any reason
12. Hemoglobin < 9g/dl
13. Absolute Neutrophil count < 1500 cells/mm3
14. Platelet count <75,000 cells/mm3.
15. Creatinine Clearance < 45 ml/min (2021 CKD-EPI)
16. Serum albumin less than or equal to 3.0g/dl
17. Bilirubin greater than or equal to 1.5 mg/dl
18. Aminotransferases levels five time above the Upper Limit of Normal (x5
times the ULN)
19. Any disorder where the patient would not tolerate placement of a dialysis
catheter, blood volume loss during an extracorporeal session or from
research blood draws per the judgment of the principal investigator.
20. Patient refuses to receive blood replacement.
21. History of allergy to heparin or heparin-induced thrombocytopenia.
22. Antibiotic or probiotic use within the 30 days prior to enrollment.
23. History of solid organ transplantation.
24. Any condition which, in the opinion of the investigator, makes the patient
a poor candidate for this clinical trial.
25. Patients may not participate in any other investigational trial while
participating in this study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA

Funding & Sponsors
Funding source category [1] 316085 0
Commercial sector/Industry
Name [1] 316085 0
Aethlon Medical Australia PTY Ltd
Country [1] 316085 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Aethlon Medical Australia PTY Ltd
Address
Country
Australia
Secondary sponsor category [1] 318251 0
None
Name [1] 318251 0
Address [1] 318251 0
Country [1] 318251 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 314906 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 314906 0
https://www.rah.sa.gov.au/research/for-researchers/central-adelaide-local-health-network-human-research-ethics-committee
Ethics committee country [1] 314906 0
Australia
Date submitted for ethics approval [1] 314906 0
24/05/2024
Approval date [1] 314906 0
Ethics approval number [1] 314906 0

Summary
Brief summary
The primary purpose of the study is to assess the safety and feasibility of using the Aethlon Hemopurifier in combination with anti-PD-1 therapy (pembrolizumab or nivolumab) for cancer patients with solid tumors.

Who is it for?
You may be eligible for this study if you are aged 18 years or older, you have been diagnosed with non-small cell lung cancer, melanoma, bladder/urinary tract cancer (urothelial cancer), renal cancer, colorectal cancer, gastric or gastroesophageal junction or esophageal cancer, head and neck cancer, cervical cancer or mesothelioma; and you have either recently begun or are going to receive treatment with pembrolizumab or nivolumab.

Study details
Participants who choose to enrol in this study will all receive the Aethlon Hemopurifier (HP) treatment, however depending upon the timing of your enrolment you may receive a different dose of the HP treatment. The maximum number of doses you may receive is one 4-hour treatment per day, on alternating days, for a total of up to three doses. You will continue to receive your scheduled pembrolizumab or nivolumab treatment during your participation in this study.

It is hoped this research will determine the optimal dosing interval for the Aethlon Hemopurifier treatment and demonstrate that this treatment can decrease the levels of exosoms associated with cancer progression. It is also hoped that the HP treatment may improve cancer patients response to anti-PD-1 therapy (pembrolizumab or nivolumab).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 133110 0
Prof Prof Michael P Brown
Address 133110 0
Royal Adelaide Hospital University of Adelaide, North Terrace, Adelaide South, Australia 5000
Country 133110 0
Australia
Phone 133110 0
+61 0870742342
Fax 133110 0
Email 133110 0
Health.CALHNResearchGovernance@sa.gov.au
Contact person for public queries
Name 133111 0
Steven P. LaRosa, MD
Address 133111 0
Aethlon Medical, Inc. 11555 Sorrento Valley Road, Suite 203, San Diego, 92121, CA
Country 133111 0
United States of America
Phone 133111 0
+16199410360
Fax 133111 0
Email 133111 0
slarosamd@aethlonmedical.com
Contact person for scientific queries
Name 133112 0
Steven P. LaRosa, MD
Address 133112 0
Aethlon Medical, Inc.; 11555 Sorrento Valley Road, Suite 203, San Diego, 92121, CA
Country 133112 0
United States of America
Phone 133112 0
+16199410360
Fax 133112 0
Email 133112 0
slarosamd@aethlonmedical.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.