Trial Outcomes & Findings for Safety & Activity of Controllable PRAME-TCR Therapy in Previously Treated AML/MDS or Metastatic Uveal Melanoma (NCT NCT02743611)
NCT ID: NCT02743611
Last Updated: 2023-10-05
Results Overview
Incidence of dose limiting-toxicity (DLT)
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
4 participants
Primary outcome timeframe
28 days after BPX-701 infusion
Results posted on
2023-10-05
Participant Flow
Participant milestones
| Measure |
Arm 1 Part 1: Does Escalation
Participants with relapsed AML or previously treated MDS received an intravenous infusion of BPX-701, starting at 1.25 x 10E6 cells/kg.
This arm had planned for dose escalations of BPX-701 until the recommended cell dose levels were reached; however, each subject only received 1 dose of BPX-701. Rimiducid was planned for subjects in response to treatment-related toxicity; however, no patients in this study received rimiducid.
BPX-701: autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch
Rimiducid: dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity
|
Arm 2 Part 1: Dose Escalation
No subjects were enrolled in this arm. See below for original arm description:
Participants with metastatic uveal melanoma will receive an intravenous infusion of BPX-701, starting at 1.5 x 10E6 cells/kg. 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.
BPX-701: autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch
Rimiducid: dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity
|
Arm 1 Part 2: Dose Expansion
No subjects were enrolled in this arm. See below for original arm description:
Participants with relapsed AML or previously treated MDS will receive an intravenous infusion of BPX-701 at the recommended cell dose level based on Arm 1 Part 1 results.
Rimiducid may be administered in response to treatment-related toxicity.
BPX-701: autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch
Rimiducid: dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity
|
Arm 2 Part 2: Dose Expansion
No subjects were enrolled in this arm. See below for original arm description:
Participants with metastatic uveal melanoma will receive an intravenous infusion of BPX-701 at the recommended cell dose level based on Arm 2 Part 2 results.
Rimiducid may be administered in response to treatment-related toxicity.
BPX-701: autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch
Rimiducid: dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
0
|
0
|
0
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
4
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Arm 1 Part 1: Does Escalation
Participants with relapsed AML or previously treated MDS received an intravenous infusion of BPX-701, starting at 1.25 x 10E6 cells/kg.
This arm had planned for dose escalations of BPX-701 until the recommended cell dose levels were reached; however, each subject only received 1 dose of BPX-701. Rimiducid was planned for subjects in response to treatment-related toxicity; however, no patients in this study received rimiducid.
BPX-701: autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch
Rimiducid: dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity
|
Arm 2 Part 1: Dose Escalation
No subjects were enrolled in this arm. See below for original arm description:
Participants with metastatic uveal melanoma will receive an intravenous infusion of BPX-701, starting at 1.5 x 10E6 cells/kg. 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.
BPX-701: autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch
Rimiducid: dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity
|
Arm 1 Part 2: Dose Expansion
No subjects were enrolled in this arm. See below for original arm description:
Participants with relapsed AML or previously treated MDS will receive an intravenous infusion of BPX-701 at the recommended cell dose level based on Arm 1 Part 1 results.
Rimiducid may be administered in response to treatment-related toxicity.
BPX-701: autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch
Rimiducid: dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity
|
Arm 2 Part 2: Dose Expansion
No subjects were enrolled in this arm. See below for original arm description:
Participants with metastatic uveal melanoma will receive an intravenous infusion of BPX-701 at the recommended cell dose level based on Arm 2 Part 2 results.
Rimiducid may be administered in response to treatment-related toxicity.
BPX-701: autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch
Rimiducid: dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity
|
|---|---|---|---|---|
|
Overall Study
Early study termination due to Sponsor discretion
|
4
|
0
|
0
|
0
|
Baseline Characteristics
Safety & Activity of Controllable PRAME-TCR Therapy in Previously Treated AML/MDS or Metastatic Uveal Melanoma
Baseline characteristics by cohort
| Measure |
Arm 1 Part 1: Does Escalation
n=4 Participants
Participants with relapsed AML or previously treated MDS received an intravenous infusion of BPX-701, starting at 1.25 x 10E6 cells/kg.
This arm had planned for dose escalations of BPX-701 until the recommended cell dose levels were reached; however, each subject only received 1 dose of BPX-701. Rimiducid was planned for subjects in response to treatment-related toxicity; however, no patients in this study received rimiducid.
BPX-701: autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch Rimiducid: dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity
No patients were enrolled in the other 3 parts of the study due to Sponsor discretion.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
|
Age, Continuous
|
68.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 28 days after BPX-701 infusionPopulation: DLT Evaluable population: all ITT subjects in Arm 1 Part 1 who complete through Day 28 or who had a DLT during the DLT evaluation period
Incidence of dose limiting-toxicity (DLT)
Outcome measures
| Measure |
DLT Population
n=3 Participants
This population includes 3 of the 4 patients who participate in Arm 1 Part 1 and completed follow-up through at least 28 days following BPX-701 infusion and were thus able to be assessed for dose-limiting toxicities.
No patients were enrolled in the other 3 parts of this study per sponsor discretion.
|
|---|---|
|
Part 1 Arm 1: Dose-limiting Toxicity
|
0 Participants
|
PRIMARY outcome
Timeframe: 15 monthsPopulation: Subjects enrolled in Arm 1 Part 1 of the study who received the planned dose of BPX-701
Number of participants with AEs and SAEs assessed for severity using CTCAE
Outcome measures
| Measure |
DLT Population
n=4 Participants
This population includes 3 of the 4 patients who participate in Arm 1 Part 1 and completed follow-up through at least 28 days following BPX-701 infusion and were thus able to be assessed for dose-limiting toxicities.
No patients were enrolled in the other 3 parts of this study per sponsor discretion.
|
|---|---|
|
Part 1 Arm 1: Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)
|
4 Participants
|
Adverse Events
Arm 1 Part 1: Dose Escalation
Serious events: 2 serious events
Other events: 4 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Arm 1 Part 1: Dose Escalation
n=4 participants at risk
Participants with relapsed AML or previously treated MDS received an intravenous infusion of BPX-701, starting at 1.25 x 10E6 cells/kg.
This arm had planned for dose escalations of BPX-701 until the recommended cell dose levels were reached; however, each subject only received 1 dose of BPX-701. Rimiducid was planned for subjects in response to treatment-related toxicity; however, no patients in this study received rimiducid.
BPX-701: autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch Rimiducid: dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity
No patients were enrolled in the other 3 parts of this study due to Sponsor discretion.
|
|---|---|
|
Infections and infestations
Pseudomonas bacteremia
|
25.0%
1/4 • Number of events 1 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
|
Vascular disorders
Orthostatic hypotension
|
25.0%
1/4 • Number of events 1 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
|
Immune system disorders
Cytokine release syndrome
|
25.0%
1/4 • Number of events 1 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
|
Infections and infestations
Neurotoxicity
|
25.0%
1/4 • Number of events 2 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
|
Cardiac disorders
Tachypnea
|
25.0%
1/4 • Number of events 1 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
|
Infections and infestations
Infection
|
25.0%
1/4 • Number of events 1 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
|
Blood and lymphatic system disorders
Neutropenic fever
|
25.0%
1/4 • Number of events 1 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
Other adverse events
| Measure |
Arm 1 Part 1: Dose Escalation
n=4 participants at risk
Participants with relapsed AML or previously treated MDS received an intravenous infusion of BPX-701, starting at 1.25 x 10E6 cells/kg.
This arm had planned for dose escalations of BPX-701 until the recommended cell dose levels were reached; however, each subject only received 1 dose of BPX-701. Rimiducid was planned for subjects in response to treatment-related toxicity; however, no patients in this study received rimiducid.
BPX-701: autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch Rimiducid: dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity
No patients were enrolled in the other 3 parts of this study due to Sponsor discretion.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
50.0%
2/4 • Number of events 2 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
25.0%
1/4 • Number of events 8 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
|
Blood and lymphatic system disorders
Anemia
|
25.0%
1/4 • Number of events 6 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
|
General disorders
Fatigue
|
75.0%
3/4 • Number of events 3 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
|
Nervous system disorders
Dizziness
|
50.0%
2/4 • Number of events 3 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
|
Vascular disorders
Deep vein thrombosis
|
25.0%
1/4 • Number of events 3 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
|
General disorders
Peripheral edema
|
50.0%
2/4 • Number of events 2 • 15 months
All AEs were to be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed for severity by the Investigator using the National Cancer Institute (NCI) CTCAE v4.03. Adverse events were to be summarized by system organ class and preferred term.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place