Source: https://www.mycancergenome.org/content/clinical_trials/NCT02743611/
Timestamp: 2019-08-25 18:19:31
Document Index: 114079246

Matched Legal Cases: ['art 1', 'art 1', 'arts 2', 'art 3', 'art 2', 'arts 2']

Clinical Trial: NCT02743611 - My Cancer Genome
https://clinicaltrials.gov/show/NCT02743611
Brief Title: Dose Finding Study Evaluating Safety in Patients With Relapsed AML, Previously Treated MDS or Metastatic Uveal Melanoma
ORG STUDY ID: BP-011
NCT ID: NCT02743611
BPX-701 BPX-701 and Rimiducid (AP1903)
Rimiducid AP1903 BPX-701 and Rimiducid (AP1903)
This study will evaluate patients with relapsed AML, previously treated MDS or metastatic uveal melanoma who will have autologous immune cells, called T cells, collected via apheresis. The T cells will be reinfused according to a dose-finding schedule after the patient has been identified as having adequate lymphopenia to provide for homeostatic expansion of the adoptively transferred, engineered T cell therapeutic product. As a safety measure, these T cells have been programmed with a self-destruct switch to remove gene-modified T cells in response to uncontrollable treatment-emergent toxicity.
A Phase 1/2, multicenter, open-label, non-randomized study of the feasibility, safety, and
clinical activity of BPX-701, a genetically modified autologous T cell product incorporating
an HLA-A2.01-restricted PRAME-directed T cell receptor (TCR) and an inducible caspase-9
(iCasp9) safety switch, when administered to subjects with relapsed AML (Arm 1), previously
treated MDS (Arm 1) or metastatic uveal melanoma (Arm 2). Arms 1 and 2 will be conducted in
parallel. For each Arm, the study will be comprised of multiple parts, beginning initially
with Part 1 (Phase 1).
Part 1 is a Cell Dose Escalation phase to identify the recommended BPX-701 cell dose for
expansion (RDE) using a 3+3 dose escalation Parts 2 and 3 comprise a Dose Expansion phase to
further assess safety, pharmacodynamics (including BPX-701 T cell persistence and response to
rimiducid as applicable), and clinical activity of BPX-701 T cells administered at the RDE.
The opening of Part 3 is dependent upon antitumor activity observed in Part 2. Within each
Arm, subjects will be monitored for clinical activity to enable early stopping for futility
if sufficient antitumor activity is not demonstrated. For each Arm, the maximum planned
enrollment in dose expansion is 40 subjects (Parts 2 and 3 combined).
BPX-701 and Rimiducid (AP1903) Experimental BPX-701: autologous T cells genetically modified to express αβ T cell receptor reacting with PRAME peptide/human leukocyte antigen (HLA)-A2.01 and containing an inducible safety switch Rimiducid (AP1903): administered to induce apoptosis of the BPX-701 T cells in the event of toxicity
1. Each subject (or their legally acceptable representative) must sign and date an
informed consent form approved by the institutional review board/ethics committee, as
appropriate, indicating that he/she understands the purpose of and procedures required
for the study and are willing to comply. Consent is to be obtained prior to the
performance of any study-specific procedures or tests that are not part of the
standard of care for the subject's disease.
2. Arm 1:
-  MDS not responding to hypomethylation therapy or recurrence after initial
response; or,
-  AML with disease relapse following first complete remission with intermediate or
adverse genetics according to the ELN criteria (Dohner 2017) - Subjects with a
prior treatment history of stem cell transplant must be >100 days post-transplant
with no evidence of active GvHD and not requiring systemic immunomodulatory or
immunosuppressive therapy defined as >10mg prednisone or equivalent per day and
active use of a calcineurin inhibitor
-  Histologically or cytologically confirmed diagnosis of metastatic uveal melanoma
-  Measurable disease (at least one target lesion) per RECIST v1.1 (Eisenhauer 2009)
-  Absolute neutrophil count ≥1,000/µL
3. HLA-A2.01 positive by local assessment
4. Documented positive myeloid blast or tumor expression of PRAME as determined by
central testing of an available, representative bone marrow aspirate (fresh sample) or
tissue specimen (formalin-fixed paraffin-embedded tissue, either from an archived
sample or fresh biopsy) for Arm 1 and Arm 2, respectively
5. Absolute lymphocyte count ≥200/μL
7. Life expectancy >12 weeks
9. Subjects must have adequate venous access for apheresis or agree to use of a central
line for apheresis collection
10. Subject has adequate organ function:
-  Cardiac: Left ventricular ejection fraction at rest must be ≥lower limit of
-  Coagulation: International normalized ratio ≤1.5
-  Direct bilirubin ≤2x upper limit of normal (ULN), or ≤3x if due to Gilbert's
-  Aspartate aminotransferase and alanine aminotransferase ≤3 x ULN, or ≤5 x ULN if
-  Renal: Creatinine ≤1.5 x ULN
11. Before planned BPX-701 T cell infusion, as well as during the study, a female subject
-  Not of childbearing potential defined as:
1. Premenarchal,
2. Postmenopausal (>45 years of age with amenorrhea ≥12 months),
3. Permanently sterilized,
4. Otherwise incapable of pregnancy; or,
-  Of childbearing potential and agrees to use 2 highly effective methods of birth
control for at least 12 months after lymphodepletion
1. Arm 1:
-  Primary refractory AML
-  Uncontrolled disseminated intravascular coagulation
-  Symptomatic or untreated central nervous system involvement by malignant cells
-  Peripheral blast count ≥20,000/μL
2. Arm 2:
-  Symptomatic, untreated or actively progressing central nervous system metastases.
Subjects with prior brain metastases treated at least 2 weeks prior to the
planned BPX-701 T cell infusion who are clinically stable and do not require
chronic corticosteroid treatment are allowed
3. Ongoing toxicities related to prior anticancer therapy that have not resolved to Grade
≤1. Current unresolved Grade ≥2 non-hematologic toxicity may be allowed following
discussion with and approval by the sponsor
4. Participation in any investigational drug study within 4 weeks prior to the planned
BPX-701 T cell infusion
5. Chemotherapy (excluding hydroxyurea), targeted therapy, or radiotherapy (excluding
palliative radiation) within 2 weeks, hydroxyurea within 1 week, or immunotherapy
within 4 weeks prior to BPX-701 T cell infusion, other than salvage/lymphodepletion
6. Active autoimmune disease requiring immunosuppressive therapy. Subjects with vitiligo;
type I diabetes; hypothyroidism, adrenal insufficiency, or hypophysitis only requiring
hormone replacement; psoriasis not requiring systemic treatment or conditions not
expected to recur; or history of Hashimoto's Thyroiditis on stable dose of thyroid
hormone replacement therapy should not be excluded
7. Impaired cardiac function or clinically significant cardiac disease, including any of
-  Symptomatic congestive heart failure requiring treatment;
-  Clinically significant cardiac arrhythmia;
-  Uncontrolled hypertension;
-  Acute myocardial infarction or unstable angina pectoris within 3 months prior to
BPX-701 T cell infusion; or,
-  Marked limitation of physical activity due to symptoms, or unable to carry on any
physical activity without discomfort (i.e., New York Heart Association Functional
Class III-IV)
8. Major surgical procedure, other than for diagnosis, within 4 weeks prior to BPX-701 T
cell infusion, or anticipation of the need for a major surgical procedure during the
9. Received a vaccine containing live virus within 4 weeks prior to the planned BPX-701 T
cell infusion. Seasonal flu vaccines that do not contain live virus are permitted
10. Treatment with systemic chronic steroid therapy (prednisone >10mg daily or equivalent)
within 7 days or 7 half-lives, whichever is shorter, prior to the planned apheresis
date (See Appendix 6 on half-lives of common corticosteroids). Local steroid therapies
(e.g., otic, ophthalmic, intra-articular or inhaled medications) are acceptable
11. Uncontrolled intercurrent illness including but not limited to poorly controlled
hypertension or diabetes, or any medical condition determined by the investigator to
be a risk for enrolling on the protocol
12. Uncontrolled infection requiring systemic therapy. Prior oral or IV antibiotics
antifungals or antiviral medications must be discontinued at least 2 weeks prior to
BPX-701 T cell infusion except for use of prophylactic antimicrobial agents
13. Active hepatitis B virus (HBV) infection (chronic or acute), defined as having a
positive hepatitis B surface antigen (HBsAg) test during Screening. Subjects with a
past or resolved HBV infection, defined as having a negative HBsAg test and a positive
total hepatitis B core antibody (HBcAb) test at screening are eligible for the study
if HBV DNA test is negative. If a patient has a negative HBsAg test and a positive
total HBcAb test at screening, an HBV DNA test should be performed
14. Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody
test followed by a positive HCV RNA test during Screening. The HCV RNA test will be
performed only for patients who have a positive HCV test
15. History of human immunodeficiency virus (HIV), or positive HIV test during Screening
(unless not permitted by local regulations)
16. Subject is a woman of child-bearing potential is pregnant (positive serum β-human
chorionic gonadotropin test at Baseline), planning to become pregnant within 12 months
after lymphodepletion or is breastfeeding
17. Subject is a man who plans to father a child within 12 months after lymphodepletion
18. Known bovine product allergy
19. Malignant disease other than that being treated in this study. Exceptions to this
exclusion are:
-  Malignancies that were treated curatively and have not recurred within 2 years
-  Completely resected basal cell and squamous cell skin cancers
-  Any malignancy considered to be indolent and that has never required therapy
Measure: Maximum tolerated dose (MTD) and/or recommended expansion dose of BPX-701 measured by dose limiting toxicities (DLTs)
Time Frame: 30 days post-treatment infusion
Description: To assess the safety and tolerability as defined by dose-limiting toxicities (DLTs) of BPX-701 T cells administered to patients expressing the HLA- A2.01 allele with relapsed AML, MDS or metastatic uveal melanoma