Safety & Activity of Controllable PRAME-TCR Therapy in Previously Treated AML/MDS or Metastatic Uveal Melanoma

Phase 1

Terminated

• Conditions: Acute Myeloid Leukemia; Uveal Melanoma; Myelodysplastic Syndrome
• Interventions: Biological: BPX-701; Drug: Rimiducid

• Registration Number: NCT02743611
• Lead Sponsor: Bellicum Pharmaceuticals

Brief Summary

The purpose of this study is to evaluate the safety and activity of BPX-701 in participants with relapsed AML, previously treated MDS, or metastatic uveal melanoma expressing high levels of PReferentially expressed Antigen in MElanoma (PRAME). Participants' T cells are modified to recognize and target the PRAME tumor marker on cancer cells.

Detailed Description

The goal of this study is to characterize the safety, feasibility, and clinical activity of BPX-701, a genetically modified autologous T cell product incorporating an HLA-A2-restricted PRAME-directed TCR and a rimiducid-inducible safety switch, when administered to subjects with relapsed AML, previously treated MDS, or metastatic uveal melanoma.

The study will be comprised of multiple parts:

Part 1 (Phase 1): Cell dose escalation to identify the maximum dose of BPX-701 T cells (escalating doses from 1.25 x 10E6 cells/kg up to 5.0 x 10E6 cells/kg to be explored) Parts 2 and 3 (Phase 2): Dose expansion to assess the safety, pharmacodynamics (including BPX-701 T cell persistence and response to rimiducid as applicable), and clinical activity at the recommended dose identified in Part 1 During Parts 1, 2, or 3, rimiducid may be administered following BPX-701 T cell infusion in response to uncontrollable, treatment-emergent toxicity

Study Timeline

• Study First Submitted: 2016-04-11
• Study First Submitted QC: 2016-04-18
• Study First Posted: 2016-04-19
• Study Start: 2017-04-14
• Primary Completion: 2019-07-19
• Study Completion: 2020-07-19
• Status Verified: 2023-06
• Results First Submitted: 2023-06-08
• Results First Submitted QC: 2023-09-12
• Last Update Submitted: 2023-09-12
• Results First Posted: 2023-10-05
• Last Update Posted: 2023-10-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1 Does Escalation	BPX-701	Participants with relapsed AML or previously treated MDS will receive an intravenous infusion of BPX-701. Dose escalation of BPX-701 will continue until the recommended cell dose level is reached. Rimiducid may be administered in response to treatment-related toxicity.
Arm 1 Does Escalation	Rimiducid	Participants with relapsed AML or previously treated MDS will receive an intravenous infusion of BPX-701. Dose escalation of BPX-701 will continue until the recommended cell dose level is reached. Rimiducid may be administered in response to treatment-related toxicity.
Arm 1 Part 2 Dose Expansion	BPX-701	Participants with relapsed AML or previously treated MDS will receive an intravenous infusion of BPX-701 at the recommended cell dose level. Rimiducid may be administered in response to treatment-related toxicity.
Arm 2 Dose Escalation	BPX-701	Participants with metastatic uveal melanoma will receive an intravenous infusion of BPX-701. Dose escalation of BPX-701 will continue until the recommended cell dose level is reached. Rimiducid may be administered in response to treatment-related toxicity.
Arm 2 Part 2 Dose Expansion	BPX-701	Participants with metastatic uveal melanoma will receive an intravenous infusion of BPX-701 at the recommended cell dose level. Rimiducid may be administered in response to treatment-related toxicity.
Arm 2 Dose Escalation	Rimiducid	Participants with metastatic uveal melanoma will receive an intravenous infusion of BPX-701. Dose escalation of BPX-701 will continue until the recommended cell dose level is reached. Rimiducid may be administered in response to treatment-related toxicity.
Arm 1 Part 2 Dose Expansion	Rimiducid	Participants with relapsed AML or previously treated MDS will receive an intravenous infusion of BPX-701 at the recommended cell dose level. Rimiducid may be administered in response to treatment-related toxicity.
Arm 2 Part 2 Dose Expansion	Rimiducid	Participants with metastatic uveal melanoma will receive an intravenous infusion of BPX-701 at the recommended cell dose level. Rimiducid may be administered in response to treatment-related toxicity.

Primary Outcome Measures

Name	Time	Method
Part 1 Arm 1: Dose-limiting Toxicity	28 days after BPX-701 infusion	Incidence of dose limiting-toxicity (DLT)
Part 1 Arm 1: Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)	15 months	Number of participants with AEs and SAEs assessed for severity using CTCAE

Trial Locations

Locations (3)

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States