Personalized Adoptive Cellular Therapy Targeting MDS Stem Cell Neoantigens (PACTN)
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|ClinicalTrials.gov Identifier: NCT03258359|
Recruitment Status : Active, not recruiting
First Posted : August 23, 2017
Last Update Posted : March 4, 2020
|Condition or disease||Intervention/treatment||Phase|
|Myelodysplastic Syndromes||Biological: PACTN||Phase 1|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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, 2020|
|Estimated Study Completion Date :||December 1, 2020|
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.
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.
- 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.
- 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
- 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
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
|United States, California|
|University of California, San Diego|
|San Diego, California, United States, 92093|
|Study Director:||Antonella Vitiello, PhD||PersImmune, Inc|