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

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. Read our disclaimer for details. Identifier: NCT03258359
Recruitment Status : Active, not recruiting
First Posted : August 23, 2017
Last Update Posted : March 4, 2020
University of California, San Diego
Information provided by (Responsible Party):
PersImmune, Inc

Tracking Information
First Submitted Date  ICMJE August 18, 2017
First Posted Date  ICMJE August 23, 2017
Last Update Posted Date March 4, 2020
Actual Study Start Date  ICMJE January 1, 2018
Estimated Primary Completion Date December 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 18, 2017)
Acute and subacture 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2017)
  • 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)
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 18, 2017)
  • 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
  • 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
  • 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
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE Personalized Adoptive Cellular Therapy Targeting MDS Stem Cell Neoantigens (PACTN)
Official Title  ICMJE A Phase 1 Clinical Trial of Personalized, Adoptive Cellular Immunotherapy Targeting Patient-specific Neoplastic Stem Cell Neoantigens (PACTN) in Patients With Myelodysplastic Syndromes (MDS)
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.
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.

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 Myelodysplastic Syndromes
Intervention  ICMJE 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.
Study Arms  ICMJE 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.
Intervention: Biological: PACTN
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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 17, 2018)
Original Estimated Enrollment  ICMJE
 (submitted: August 18, 2017)
Estimated Study Completion Date  ICMJE December 1, 2020
Estimated Primary Completion Date December 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03258359
Other Study ID Numbers  ICMJE PACTN-02
Has Data Monitoring Committee Yes
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 PersImmune, Inc
Study Sponsor  ICMJE PersImmune, Inc
Collaborators  ICMJE University of California, San Diego
Investigators  ICMJE
Study Director: Antonella Vitiello, PhD PersImmune, Inc
PRS Account PersImmune, Inc
Verification Date March 2020

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