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

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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