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Safety of AV-MEL-1 With Anti-PD-1 Therapy in Metastatic Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03743298
Recruitment Status : Recruiting
First Posted : November 16, 2018
Last Update Posted : May 3, 2021
Information provided by (Responsible Party):
Aivita Biomedical, Inc.

Tracking Information
First Submitted Date  ICMJE November 13, 2018
First Posted Date  ICMJE November 16, 2018
Last Update Posted Date May 3, 2021
Actual Study Start Date  ICMJE April 21, 2021
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2018)
Primary Safety Endpoint: Number of grade 3-5 adverse events with AV-MEL-1 + PD-1 versus PD-1 alone [ Time Frame: 3 years ]
Determine whether combining AV-MEL-1 with anti-PD-1 is associated with increased risk as defined by AEs per NCI common toxicity criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Safety of AV-MEL-1 With Anti-PD-1 Therapy in Metastatic Melanoma
Official Title  ICMJE Phase 1B Trial of AV-MEL-1 (Autologous Dendritic Cells Loaded With Autologous Tumor Antigens) With Anti-PD-1 Checkpoint Inhibitors in Metastatic Melanoma
Brief Summary This is an open label, single-arm, phase IB treatment study to determine the safety of administering anti-PD1 monoclonal antibodies with AV-MEL-1 and to get some suggestion of efficacy, in patients with measurable metastatic melanoma. These will be patients who have either never received treatment for metastatic melanoma or were previously treated with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations, and are about to initiate anti-PD1 monotherapy. The intent is to treat 14 to 20 patients with the combination of anti-PD-1 and AV-MEL-1.
Detailed Description

The sequence is as follows:

  1. Patients will provide consent for collection of blood and tumor, performance of leukapheresis, and intended plan to treat with a standard anti-PD-1 regimen, and to treat with their patient-specific AV-MEL-1 once it has been manufactured.
  2. Prior to starting anti-PD-1 therapy, surgically resected tumor tissue will be sent to AIVITA Biomedical where it will be processed to establish a short-term cell line of autologous tumor cells. Approximately 1 cm3 of surgically excised tumor is preferred. Whenever possible the tissue should be obtained from a lesion no greater than 2 cm in longest diameter. Part of the sample should be assessed by pathologists to confirm melanoma and to test for PDL-1 expression.
  3. Prior to starting anti-PD-1 therapy, patients will undergo leukapheresis to obtain peripheral blood mononuclear cells that will be converted into dendritic cells (DC).
  4. Patients will initiate anti-PD-1 therapy monotherapy (e.g. pembrolizumab or nivolumab) using standard doses and schedules of administration.
  5. When the vaccine is ready, which will take approximately 8 weeks from the date of tumor resection, and the patient has had the opportunity to have received about two months of anti-PD-1 monotherapy, it is expected per standard of care that the patient will undergo radiographic assessment to classify disease status and response (if there was measurable disease at baseline) to the anti-PD-1 therapy.
  6. Starting week 10, AV-MEL-1 will be given concurrently with continuation of the anti-PD-1 therapy. AV-MEL-1 injections will be given weekly for 3 weeks, (weeks 10-12, then monthly at weeks 16, 20, 24, 28, and 32). Blood will be collected from patients prior to each injection for immune monitoring tests.
  7. If anti-PD-1 therapy is discontinued during vaccine treatment, the remaining vaccine doses may still be administered at the discretion of the patient's managing physician.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Melanoma
Intervention  ICMJE Drug: AV-MEL-1
AV-MEL-1: Autologous dendritic cells loaded with autologous tumor antigens (ATA) from a short-term cell culture of autologous tumor cells. AV-MEL-1 is admixed with granulocyte-macrophage colony stimulating factor (GM-CSF) as an adjuvant, prior to injection.
Study Arms  ICMJE Experimental: AV-MEL-1
AV-MEL-1: Autologous dendritic cells loaded with autologous tumor antigens (ATA) from a short-term cell culture of autologous tumor cells. AV-MEL-1 is admixed with granulocyte-macrophage colony stimulating factor (GM-CSF) as an adjuvant, prior to injection.
Intervention: Drug: AV-MEL-1
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 15, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2024
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age > 18
  • Karnofsky Performance Status (KPS) of > 70
  • Histologic diagnosis of metastatic melanoma
  • Presence of at least one metastatic lesion that is to be removed surgically as part of standard care (e.g. diagnosis or diagnostic testing, mono- or oligometastatic disease, alleviation of symptoms etc)
  • Considered appropriate for standard anti-PD1 antibody monotherapy by managing physician
  • Given written informed consent to participate in the study

Exclusion Criteria:

  • Known to have active hepatitis B or C or HIV (need not be screened)
  • KPS of < 70; see Appendix A
  • Known underlying cardiac disease associated with myocardial dysfunction that requires active medical treatment, or unstable angina related to atherosclerotic cardiovascular disease, or under treatment for arterial or venous peripheral vascular disease
  • Diagnosis of any other invasive cancer or other disease process which is considered to be life-threatening within the next five years, and/or taking anti-cancer therapy for cancer other than melanoma
  • Active infection or other active medical condition that could be eminently life-threatening, including active blood clotting or bleeding diathesis.
  • Known autoimmune disease, immunodeficiency, or disease process that involves the chronic or intermittent use of immunosuppressive therapy
  • Uncontrolled brain or spinal cord metastases or active leptomingeal metastatic disease.
  • Received another investigational drug within 28 days of the first dose or are planning to receive another investigational drug while receiving this investigational treatment
  • Previous anti-cancer treatment for melanoma, other than BRAF/MEK inhibittion.
  • Known hypersensitivity to GM-CSF
  • Pregnancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Candace Hsieh, PhD 949-872-2555 ext 110
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03743298
Other Study ID Numbers  ICMJE CL-MEL-P01-US
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Aivita Biomedical, Inc.
Study Sponsor  ICMJE Aivita Biomedical, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Robert O Dillman, MD Aivita Biomedical, Inc.
PRS Account Aivita Biomedical, Inc.
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP