Acute Myeloid LeukemiaPhase 1/2NCT02743611
Safety & Activity of Controllable PRAME-TCR Therapy in Previously Treated AML/MDS or Metastatic Uveal Melanoma
A Phase 1/2 study testing BPX-701 and Rimiducid in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Bellicum Pharmaceuticals at 3 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndrome, Uveal Melanoma
- What is being tested?
- BPX-701 and Rimiducid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 3 sitesUnited States
- Study dates
- 14 Apr 2017to 19 Jul 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Tennessee Oncology
Nashville, Tennessee, 37203
Oregon Health & Science University
Portland, Oregon, 97239
About this study
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
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.
Read the 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
- Being tested
- BPX-701, Rimiducid
- Keywords
- BPX-701, AP1903, rimiducid, AML, MDS, relapsed AML, uveal melanoma, PRAME
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BPX-701Biological
autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch
RimiducidDrug
Also called AP1903
dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: BPX-701; Drug: Rimiducid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1 Arm 1: Dose-limiting Toxicity
Incidence of dose limiting-toxicity (DLT)
Measured: 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
Measured: 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2016 (estimated)
- Study start14 Apr 2017
- Primary completion19 Jul 2019
- Study completion19 Jul 2020
Why it stopped: company decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bellicum Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Contact Contact for Clinical Trials, Study director, Bellicum Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02743611
- Sponsor's protocol ID
- BP-011
- Status last verified
- Jun 2023
- First submitted
- 11 Apr 2016
- Last updated
- 5 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02743611
- Acronym / sponsor ID
- BP-011
- Keywords
- BPX-701, AP1903, rimiducid, AML, MDS, relapsed AML, uveal melanoma, PRAME
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: company decision
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Bellicum PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 14 Apr 2017 (actual)
- Primary completion
- 19 Jul 2019 (actual)
- Study completion
- 19 Jul 2020 (actual)
- First posted
- 19 Apr 2016 (estimated)
- Results
- Posted 5 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm 1 Does Escalation | Experimental | Biological: BPX-701, Drug: RimiducidParticipants 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. |
| Arm 2 Dose Escalation | Experimental | Biological: BPX-701, Drug: RimiducidParticipants 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. |
| Arm 1 Part 2 Dose Expansion | Experimental | Biological: BPX-701, Drug: RimiducidParticipants 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. |
| Arm 2 Part 2 Dose Expansion | Experimental | Biological: BPX-701, Drug: RimiducidParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (15 listed)
- Participants with AML must not have:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BPX-701autologous T cells genetically modified to express the αβ TCR reacting with PRAME peptide/HLA-A2.01 (PRAME TCR) and an inducible safety switch | Biological | Arm 1 Does Escalation, Arm 1 Part 2 Dose Expansion, Arm 2 Dose Escalation, Arm 2 Part 2 Dose Expansion |
| RimiducidAlso: AP1903dimerizer infusion to activate the safety switch and induce apoptosis of the BPX-701 T cells in the event of toxicity | Drug | Arm 1 Does Escalation, Arm 1 Part 2 Dose Expansion, Arm 2 Dose Escalation, Arm 2 Part 2 Dose Expansion |
Primary outcome
Part 1 Arm 1: Dose-limiting Toxicity
Time frame: 28 days after BPX-701 infusion
Incidence of dose limiting-toxicity (DLT)
Part 1 Arm 1: Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)
Time frame: 15 months
Number of participants with AEs and SAEs assessed for severity using CTCAE
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Contact Contact for Clinical Trials study director
Bellicum Pharmaceuticals
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BPX-701 and Rimiducid in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Bellicum Pharmaceuticals at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1 Arm 1: Dose-limiting Toxicity (time frame: 28 days after BPX-701 infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2023.