Acute Myeloid Leukemia, Myelodysplastic Syndrome, Uveal Melanoma
Conditions
Keywords
BPX-701, AP1903, rimiducid, AML, MDS, relapsed AML, uveal melanoma, PRAME
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
Interventions
BIOLOGICALBPX-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
DRUGRimiducid
dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity
Sponsors
Bellicum Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent 2. Participants in Arm 1: MDS not responding to hypomethylation therapy or recurrence after initial response AML with disease relapse following first complete remission with intermediate or adverse genetics according to the European Leukemia Net criteria. AML participants with prior stem cell transplant must be \>100 days post-transplant with no evidence of active graft-versus-host disease and not requiring systemic immunomodulatory or immunosuppressive therapy (\>10mg prednisone daily or treatment with a calcineurin inhibitor) 3. Participants in Arm 2: Metastatic uveal melanoma with a radiographically measurable tumor, absolute neutrophil count \>/=1000/uL, and platelets \>/=75,000/uL 4. HLA-A2.01 positive by local testing 5. Tumor with positive PRAME expression by central testing 6. Age \>/= 18 years 7. Participant has a life expectancy \>12 weeks and is able to carry out daily life activities without difficulty (Eastern Cooperative Oncology Group performance status 0 or 1). 8. Participant has adequate venous access for apheresis or agrees to use of a central line for blood collection. 9. Participant does not have significant side effects from previous anticancer treatment. 10. Adequate organ function including absolute lymphocyte count \>/=200/uL. 11. Sexually active participants must use medically acceptable methods of contraception for at least 1 year after study treatment.
Exclusion criteria
1. Participants with AML must not have: * Acute promyelocytic leukemia, * Primary refractory disease, * Uncontrolled disseminated intravascular coagulation, * Signs or symptoms of cancer cells in the brain or nervous system, * Peripheral blast count \>/=20,000/uL 2. Participants with uveal melanoma must not have an untreated brain tumor 3. Participant has a history of major surgery or treatment with other cancer therapy within 2-4 weeks (1 week for hydroxyurea) before study treatment. 4. Participant has an active, autoimmune disease that requires immunosuppressive therapy. Exceptions are vitiligo, type I diabetes, certain cases of hypothyroidism and psoriasis, or Hashimoto's thyroiditis on a stable dose of thyroid replacement therapy 5. History of clinically significant heart problems. 6. Current severe, uncontrolled systemic disease including an ongoing, active infection requiring treatment with antibiotics within 2 weeks before study treatment. 7. Participant is currently pregnant or breastfeeding. 8. Participant requires chronic, systemic steroid therapy. 9. Participant is positive for Hepatitis B, Hepatitis C, HIV, syphilis, West Nile virus, or Chagas disease. 10. Participant has side effects from earlier cancer treatment that have not resolved
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
No patients were enrolled in the other 3 parts of the study due to Sponsor discretion. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Early study termination due to Sponsor discretion | 4 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm 1 Part 1: Does Escalation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 68.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 4 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 2 / 4 |
Outcome results
Primary
Part 1 Arm 1: Dose-limiting Toxicity
Incidence of dose limiting-toxicity (DLT)
Time frame: 28 days after BPX-701 infusion
Population: 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DLT Population | Part 1 Arm 1: Dose-limiting Toxicity | 0 Participants |
Primary
Part 1 Arm 1: Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)
Number of participants with AEs and SAEs assessed for severity using CTCAE
Time frame: 15 months
Population: Subjects enrolled in Arm 1 Part 1 of the study who received the planned dose of BPX-701
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DLT Population | Part 1 Arm 1: Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs) | 4 Participants |