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Personalized Adoptive Cellular Therapy Targeting MDS Stem Cell Neoantigens (PACTN)

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ClinicalTrials.gov Identifier: NCT03258359
Recruitment Status : Recruiting
First Posted : August 23, 2017
Last Update Posted : September 19, 2018
Sponsor:
Collaborator:
University of California, San Diego
Information provided by (Responsible Party):
PersImmune, Inc

Brief Summary:
This study will evaluate the safety of autologous T cells that have been immunized ex vivo with patient-specific MDS stem cell neoantigens in patients with MDS.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Biological: PACTN Phase 1

Detailed Description:

PACTN is manufactured by a novel method to employ cancer-specific somatic variants (mutations) as a means to immunize autologous T lymphocytes to specifically kill cancer cells bearing the protein products of the mutations.

The PACTN method is based on the premise that somatic DNA mutations that cause cancer often give rise to proteins with an altered amino acid sequence. Peptides derived from these proteins, if expressed in the context of MHC Class I or II may be perceived as "non-self" by the immune system; that is, they may be perceived as neoantigens (aka, neoepitopes). Such neoantigens could therefore serve as immunogenic targets for the development of patient-specific, personalized T cell mediated immunotherapy.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Clinical Trial of Personalized, Adoptive Cellular Immunotherapy Targeting Patient-specific Neoplastic Stem Cell Neoantigens (PACTN) in Patients With Myelodysplastic Syndromes (MDS)
Actual Study Start Date : January 1, 2018
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : December 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PACTN
Open label 3+3 dose escalation phase 1 trial; 200 to 1000 mL of immunized T cells infused at 0.3, 1, and 3 x 10e7 nucleated cells/kg body weight.
Biological: PACTN
To treat patients with MDS who have failed treatment with hypomethylating agents or have relapsed after treatment with hypomethylating agents or have declined hypomethylating therapy.




Primary Outcome Measures :
  1. Acute and subacute toxicities and AEs [ Time Frame: baseline to four weeks after infusion ]
    The incidence of dose limiting toxicities (DLTs) after PACTN infusion will be used to determine the maximum tolerated dose (MTD). Adverse effects (AEs) and in particular cytokine release syndrome (CRS) and potential autoimmune AEs will be monitored.


Secondary Outcome Measures :
  1. Persistence, abundance, and activity of PACTN [ Time Frame: Samples will be collected on days 1, 4, 8, 15, 36, and 57, and then 3, 6, and 12 months ]
    Determined by quantity of PACTN in the subject's blood sample, assessed by the unique phenotype of PACTN lymphocytes and by functional measurement of PACTN activity (antigen-specific cytotoxicity)

  2. Disease Response [ Time Frame: Samples will be collected between day 29 and 43, and then at 3, 6, and 12 months ]
    Disease response will be assessed by International Working Group (IWG) criteria on bone marrow aspiration

  3. Overall and progression-free survival of subjects who receive PACTN [ Time Frame: Six and 12 months after PACTN infusion ]
    Incidence of subjects who are alive, and both alive and disease - free will be assessed at 6 and 12 months


Other Outcome Measures:
  1. The duration of hematologic response, if any [ Time Frame: Up to 12 months ]
    Assessed by measurements of blood counts during subject follow-up, employing IWG criteria

  2. PACTN persistence or peak abundance and clinical response [ Time Frame: 6 months and 1 year ]
    The grouped data on the clinical response and the 6 month and 1-year survival will be analyzed to assess if there is an association between PACTN persistence or peak abundance in blood, and either extent or duration of clinical response or subject survival

  3. Changes in Variant allele frequency (VAF) of somatic mutations targeted by PACTN [ Time Frame: From 4 days up to 1 year ]
    VAFs of targeted mutations will be assessed in blood and marrow after PACTN infusion



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of MDS according to the French-American-British (FAB) criteria. Subjects with MDS must have intermediate, high, or very high risk IPSS-R scores and cytopenia of at least one lineage.
  • Relapsed/refractory disease, or inadequate response to at least 6 cycles of hypomethylating (HMA) therapy or subjects who decline HMA therapy. Subjects must not have received any MDS or AML directed therapy for >28 days prior to receiving the study treatment.
  • Subjects who have opted not to undergo allogeneic hematopoietic stem cell transplantation or for whom no donor is available and who are not deemed eligible for high intensity chemotherapy.
  • Age >18 year at the time of obtaining informed consent, male or female.
  • An Eastern Cooperative Oncology Grou (ECOG) performance status score of 0, 1, or 2.
  • Adequate organ function.
  • Seronegative test for HIV-1/2 and hepatitis C antibodies (HCV), and a negative test for Hepatitis B antigen (HBsAg). If hepatitis C antibody test is positive, then the subject must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
  • Women of childbearing potential must have negative pregnancy test prior to initiating study treatment.
  • Life expectancy >6 months at time of screening.
  • Ability to adhere to the protocol requirements and study visit schedule.

Exclusion Criteria:

  • Subjects who anticipate use of other investigational or non-investigational agents for the treatment of MDS during the study period, aside from a stable dose of erythropoietin stimulating agent started >8 weeks prior to screening for this study.
  • Subjects who have received investigational agents, cytotoxic chemotherapy, or radiotherapy within 28 days prior to entering the study, or who have not recovered from AEs dur to agents administered more than 28 days earlier.
  • Subjects who are less than 21 days from surgery or have insufficient recovery from surgical-related trauma or wound healing.
  • Prior history of allogeneic hematopoietic stem cell transplantation.
  • Current use of granulocyte colony-stimulating factory (G-CSF) or GM-CSF.
  • History of major organ autoimmune disease.
  • Concurrent immunosuppressive therapy. A stable dose of prednisone <10 mg daily or inhaled corticosteroids are allowed.
  • Any form of primary immunodeficiency.
  • Active bacillus tuberculosis (TB) or any other active or uncontrolled infection.
  • Pior history of treated malignancy in the past 2 years. Subjects with non-melanoma skin cancer, localized prostate cancer, and carcinoma in situ of the breast of cervix are allowed.
  • Impaired cardiac function.
  • Pregnant women are excluded from this study as the proposed treatment has not been well studied in pregnant subjects.
  • Any other medical or psychiatric disorders, or social situation, that would, in the investigator's opinion, place the subject at unacceptable risk if he/she participates in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03258359


Contacts
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Contact: Rafael Bejar, MD 858-822-5485 rabejar@ucsd.edu
Contact: Tiffany Tanaka, MD 858-534-8575 tntanaka@ucsd.edu

Locations
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United States, California
University of California, San Diego Recruiting
San Diego, California, United States, 92093
Contact: Rafael Bejar, MD    858-822-5485    rabejar@ucsd.edu   
Contact: Tiffany Tanaka, MD    858-534-8575    tntanaka@ucsd.edu   
Principal Investigator: Rafael Bejar, MD         
Sub-Investigator: Tiffany Tanaka, MD         
Sponsors and Collaborators
PersImmune, Inc
University of California, San Diego
Investigators
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Study Director: Antonella Vitiello, PhD PersImmune, Inc

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Responsible Party: PersImmune, Inc
ClinicalTrials.gov Identifier: NCT03258359     History of Changes
Other Study ID Numbers: PACTN-02
First Posted: August 23, 2017    Key Record Dates
Last Update Posted: September 19, 2018
Last Verified: September 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by PersImmune, Inc:
MDS

Additional relevant MeSH terms:
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Syndrome
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms