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

NCT03258359 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: PACTN-02
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Myelodysplastic Syndromes

Keywords

MDS

Outcome Measures

Primary Outcomes (1)

• Acute and subacute toxicities and AEs

  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.

  baseline to four weeks after infusion

Secondary Outcomes (3)

• Persistence, abundance, and activity of PACTN

  Samples will be collected on days 1, 4, 8, 15, 36, and 57, and then 3, 6, and 12 months

• Disease Response

  Samples will be collected between day 29 and 43, and then at 3, 6, and 12 months

• Overall and progression-free survival of subjects who receive PACTN

  Six and 12 months after PACTN infusion

Other Outcomes (3)

• The duration of hematologic response, if any

  Up to 12 months

• PACTN persistence or peak abundance and clinical response

  6 months and 1 year

• Changes in Variant allele frequency (VAF) of somatic mutations targeted by PACTN

  From 4 days up to 1 year

Study Arms (1)

PACTN

EXPERIMENTAL

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

Interventions

PACTN BIOLOGICAL

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.

PACTN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PersImmune, Inc: lead
• University of California, San Diego: collaborator

Study Sites (1)

University of California, San Diego

San Diego, California, 92093, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Antonella Vitiello, PhD

  PersImmune, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2017
• First Posted: August 23, 2017
• Study Start: January 1, 2018
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: March 4, 2020

Record last verified: 2020-03

Locations

US (1)