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

NCT02743611 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: BP-011
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome; Uveal Melanoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Part 1 Arm 1: Dose-limiting Toxicity

  Incidence of dose limiting-toxicity (DLT)

  28 days after BPX-701 infusion

• 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

  15 months

Study Arms (4)

Arm 1 Does Escalation

EXPERIMENTAL

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; Drug: Rimiducid

Arm 2 Dose Escalation

EXPERIMENTAL

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; Drug: Rimiducid

Arm 1 Part 2 Dose Expansion

EXPERIMENTAL

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; Drug: Rimiducid

Arm 2 Part 2 Dose Expansion

EXPERIMENTAL

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; Drug: Rimiducid

Interventions

BPX-701 BIOLOGICAL

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

Arm 1 Does Escalation; Arm 1 Part 2 Dose Expansion; Arm 2 Dose Escalation; Arm 2 Part 2 Dose Expansion

Rimiducid DRUG

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

Also known as: AP1903

Arm 1 Does Escalation; Arm 1 Part 2 Dose Expansion; Arm 2 Dose Escalation; Arm 2 Part 2 Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bellicum Pharmaceuticals: lead

Study Sites (3)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Uveal Melanoma

Interventions

AP 1903 reagent

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Results Point of Contact

• Title: Contact for Clinical Trials
• Organization: Bellicum

clinicaltrials@bellicum.com

(832) 384-1100

Study Officials

• Contact Contact for Clinical Trials

  Bellicum Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2016
• First Posted: April 19, 2016
• Study Start: April 14, 2017
• Primary Completion: July 19, 2019
• Study Completion: July 19, 2020
• Last Updated: October 5, 2023
• Results First Posted: October 5, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)