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

Sponsor

Bellicum Pharmaceuticals (Industry)

Overall Status

Unknown status

CT.gov ID

NCT02743611

Collaborator

(none)

Enrollment

Locations

Arms

39.2

Anticipated Duration (Months)

9.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Myelodysplastic Syndrome Uveal Melanoma	Biological: BPX-701 Drug: Rimiducid	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Masking Description:

Open Label

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Dose-Finding Study to Evaluate the Safety, Feasibility, and Activity of BPX-701, a Controllable PRAME T-Cell Receptor Therapy, in HLA-A2+ Subjects With AML, Previously Treated MDS, or Metastatic Uveal Melanoma

Actual Study Start Date :

Apr 14, 2017

Actual Primary Completion Date :

Jul 19, 2019

Anticipated Study Completion Date :

Jul 19, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Does Escalation 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.	Biological: 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 Drug: Rimiducid dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity Other Names: AP1903
Experimental: Arm 2 Dose Escalation 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.	Biological: 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 Drug: Rimiducid dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity Other Names: AP1903
Experimental: Arm 1 Part 2 Dose Expansion 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.	Biological: 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 Drug: Rimiducid dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity Other Names: AP1903
Experimental: Arm 2 Part 2 Dose Expansion 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.	Biological: 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 Drug: Rimiducid dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity Other Names: AP1903

Outcome Measures

Primary Outcome Measures

Part 1 Arm 1: Dose-limiting toxicity [28 days after BPX-701 infusion]
Incidence of dose limiting toxicity
Part 1 Arm 1: Treatment-emergent adverse events (AEs) and serious AEs (SAEs) [180 days after BPX-701 treatment up to 15 years]
Number of participants with AEs and SAEs assessed for severity using CTCAE
Part 1 Arm 2: Dose-limiting toxicity [28 days after BPX-701 infusion]
Incidence of dose limiting toxicity
Part 1 Arm 2: Treatment-emergent adverse events (AEs) and serious AEs (SAEs) [180 days after BPX-701 treatment up to 15 years]
Number of participants with AEs and SAEs assessed for severity using CTCAE
Part 2 Arm 1: Remission rate [1 year after BPX-701 treatment]
Percentage of AML participants with complete remission (including CR without minimal residual disease, CR, and incomplete CR) per European Leukemia Net criteria; or percentage of MDS participants with CR (including marrow CR) or partial remission according to the International Working Group criteria for MDS
Part 2 Arm 2: Overall response rate [1 year after BPX-701 treatment]
Percentage of uveal melanoma participants with objective response determined by the investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Signed informed consent
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)

Participants in Arm 2:

Metastatic uveal melanoma with a radiographically measurable tumor, absolute neutrophil count >/=1000/uL, and platelets >/=75,000/uL

HLA-A2.01 positive by local testing
Tumor with positive PRAME expression by central testing
Age >/= 18 years
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).
Participant has adequate venous access for apheresis or agrees to use of a central line for blood collection.
Participant does not have significant side effects from previous anticancer treatment.
Adequate organ function including absolute lymphocyte count >/=200/uL.
Sexually active participants must use medically acceptable methods of contraception for at least 1 year after study treatment.

Exclusion Criteria

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

Participants with uveal melanoma must not have an untreated brain tumor
Participant has a history of major surgery or treatment with other cancer therapy within 2-4 weeks (1 week for hydroxyurea) before study treatment.
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
History of clinically significant heart problems.
Current severe, uncontrolled systemic disease including an ongoing, active infection requiring treatment with antibiotics within 2 weeks before study treatment.
Participant is currently pregnant or breastfeeding.
Participant requires chronic, systemic steroid therapy.
Participant is positive for Hepatitis B, Hepatitis C, HIV, syphilis, West Nile virus, or Chagas disease.
Participant has side effects from earlier cancer treatment that have not resolved

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
2	Oregon Health & Science University	Portland	Oregon	United States	97239
3	Tennessee Oncology	Nashville	Tennessee	United States	37203