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

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ClinicalTrials.gov Identifier: NCT02743611
Recruitment Status : Recruiting
First Posted : April 19, 2016
Last Update Posted : November 19, 2018
Sponsor:
Information provided by (Responsible Party):
Bellicum Pharmaceuticals

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 116 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 : April 14, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


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 Name: 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 Name: 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 Name: 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 Name: AP1903




Primary Outcome Measures :
  1. Part 1 Arm 1: Dose-limiting toxicity [ Time Frame: 28 days after BPX-701 infusion ]
    Incidence of dose limiting toxicity

  2. Part 1 Arm 1: Treatment-emergent adverse events (AEs) and serious AEs (SAEs) [ Time Frame: 180 days after BPX-701 treatment up to 15 years ]
    Number of participants with AEs and SAEs assessed for severity using CTCAE

  3. Part 1 Arm 2: Dose-limiting toxicity [ Time Frame: 28 days after BPX-701 infusion ]
    Incidence of dose limiting toxicity

  4. Part 1 Arm 2: Treatment-emergent adverse events (AEs) and serious AEs (SAEs) [ Time Frame: 180 days after BPX-701 treatment up to 15 years ]
    Number of participants with AEs and SAEs assessed for severity using CTCAE

  5. Part 2 Arm 1: Remission rate [ Time Frame: 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

  6. Part 2 Arm 2: Overall response rate [ Time Frame: 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02743611


Contacts
Contact: Bellicum Pharmaceuticals Clinical Development (832) 384-1100 medcommsmail011@bellicum.com

Locations
United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Principal Investigator    720-754-4890    Rob.gordon@sarahcannon.com   
United States, Michigan
Barbara Ann Karmanos Cancer Institute Not yet recruiting
Detroit, Michigan, United States, 48201
Contact: Principal Investigator    313-576-9271    ventimim@karmanos.org   
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Principal Investigator    503-494-7386    coora@ohsu.edu   
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Principal Investigator    615-329-7274    wdonnellan@tnonc.com   
United States, Texas
Texas Transplant Institute Not yet recruiting
San Antonio, Texas, United States, 78229
Contact: Principal Investigator    210-575-7278      
Sponsors and Collaborators
Bellicum Pharmaceuticals
Investigators
Study Director: Bellicum Pharmaceuticals Senior Director Clinical Development

Responsible Party: Bellicum Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02743611     History of Changes
Other Study ID Numbers: BP-011
First Posted: April 19, 2016    Key Record Dates
Last Update Posted: November 19, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bellicum Pharmaceuticals:
BPX-701
AP1903
rimiducid
AML
MDS
relapsed AML
uveal melanoma
PRAME

Additional relevant MeSH terms:
Melanoma
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Leukemia, Myeloid
Leukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases