Brief Title
Safety & Activity of Controllable PRAME-TCR Therapy in Previously Treated AML/MDS or Metastatic Uveal Melanoma
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
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 Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Part 1 Arm 1: Dose-limiting toxicity
Condition
Acute Myeloid Leukemia
Intervention
BPX-701
Study Arms / Comparison Groups
Arm 1 Does Escalation
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
28
Start Date
April 14, 2017
Completion Date
July 19, 2020
Primary Completion Date
July 19, 2019
Eligibility Criteria
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Bellicum Pharmaceuticals Senior Director, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02743611
Organization ID
BP-011
Responsible Party
Sponsor
Study Sponsor
Bellicum Pharmaceuticals
Study Sponsor
Bellicum Pharmaceuticals Senior Director, Study Director, Clinical Development
Verification Date
October 2019