Clinical Trials /

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

NCT03258359

Description:

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.

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Personalized Adoptive Cellular Therapy Targeting MDS Stem Cell Neoantigens (PACTN)
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: PACTN-02
  • NCT ID: NCT03258359

Conditions

  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
PACTNPACTN

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
PACTNExperimentalOpen 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.
  • PACTN

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Acute and subacute toxicities and AEs
Time Frame:baseline to four weeks after infusion
Safety Issue:
Description: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

Measure: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
Safety Issue:
Description: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)
Measure:Disease Response
Time Frame:Samples will be collected between day 29 and 43, and then at 3, 6, and 12 months
Safety Issue:
Description:Disease response will be assessed by International Working Group (IWG) criteria on bone marrow aspiration
Measure:Overall and progression-free survival of subjects who receive PACTN
Time Frame:Six and 12 months after PACTN infusion
Safety Issue:
Description:Incidence of subjects who are alive, and both alive and disease - free will be assessed at 6 and 12 months

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:PersImmune, Inc

Trial Keywords

  • MDS

Last Updated

September 17, 2018