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

Primary Purpose

Acute Myeloid Leukemia, Myelodysplastic Syndrome, Uveal Melanoma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

BPX-701

Rimiducid

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring BPX-701, AP1903, rimiducid, AML, MDS, relapsed AML, uveal melanoma, PRAME

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Colorado Blood Cancer Institute
Oregon Health & Science University
Tennessee Oncology

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Arm 1 Does Escalation

Arm 2 Dose Escalation

Arm 1 Part 2 Dose Expansion

Arm 2 Part 2 Dose Expansion

Arm 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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Part 1 Arm 1: Dose-limiting Toxicity

Incidence of dose limiting-toxicity (DLT)

Part 1 Arm 1: Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)

Number of participants with AEs and SAEs assessed for severity using CTCAE

Secondary Outcome Measures

Full Information

NCT ID

NCT02743611

First Posted

April 11, 2016

Last Updated

September 12, 2023

Sponsor

Bellicum Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02743611

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Terminated

Why Stopped

company decision

Study Start Date

April 14, 2017 (Actual)

Primary Completion Date

July 19, 2019 (Actual)

Study Completion Date

July 19, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bellicum Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia, Myelodysplastic Syndrome, Uveal Melanoma

Keywords

BPX-701, AP1903, rimiducid, AML, MDS, relapsed AML, uveal melanoma, PRAME

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Masking Description

Open Label

Allocation

Non-Randomized

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1 Does Escalation

Arm Type

Experimental

Arm Description

Arm Title

Arm 2 Dose Escalation

Arm Type

Experimental

Arm Description

Arm Title

Arm 1 Part 2 Dose Expansion

Arm Type

Experimental

Arm Description

Arm Title

Arm 2 Part 2 Dose Expansion

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

BPX-701

Intervention Description

autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch

Intervention Type

Drug

Intervention Name(s)

Rimiducid

Other Intervention Name(s)

AP1903

Intervention Description

dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity

Primary Outcome Measure Information:

Title

Part 1 Arm 1: Dose-limiting Toxicity

Description

Incidence of dose limiting-toxicity (DLT)

Time Frame

28 days after BPX-701 infusion

Title

Part 1 Arm 1: Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)

Description

Number of participants with AEs and SAEs assessed for severity using CTCAE

Time Frame

15 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Contact Contact for Clinical Trials

Organizational Affiliation

Bellicum Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Colorado Blood Cancer Institute

City

Denver

State/Province

Colorado

ZIP/Postal Code

80218

Country

United States

Facility Name

Oregon Health & Science University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

Tennessee Oncology

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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