Hematologic MalignancyPhase 1NCT03459170
Safety/PK Study of Gene Modified Donor T Cell Infusion in Children With Recurrent Hem Malignancies After Allo Transplant
A Phase 1 study testing BPX-501 T cells and rimiducid in people with Hematologic Malignancy, run by Bellicum Pharmaceuticals at 3 sites in Italy.
Trial summary
Phase I, open-label, non-randomized study of safety, pharmacokinetics and efficacy of donor BPX-501 T cell infusion in children with recurrent or minimal residual disease (MRD) hematologic malignancies post-allogeneic transplant. The study will consist of the Main Study and an optional Pharmacokinetics (PK) Sub-Study. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Hematologic Malignancy
- What is being tested?
- BPX-501 T cells and rimiducid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 3 sitesItaly
- Study dates
- 1 Feb 2018to Sep 2035
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients aged < 18
- Clinical diagnosis of one of the following pediatric hematological malignancies:
- High-risk Acute Leukemia (Acute lymphoblastic leukemia [ALL] or acute myeloid leukemia [AML]) in any CR
- Acute Leukemia that is minimal residual disease (MRD) positive at > 1copy per 1 x 10,000 reference copies pre-HSCT
- Myelodysplastic Syndrome (MDS)
- Hodgkin or Non-Hodgkin lymphomas
Show all 32Show fewer
- Other high-risk hematological malignancy in CR eligible for stem cell transplantation per institutional standard
- Patients with a hematological malignancy who have received a prior allogeneic HSCT
- Patients with on-treatment relapse of AML within 6 months of initial CR
- Patients relapsing within 6 months of initial diagnosis of hematological malignancy.
- Planned or previous treatment of hematological malignancy with one of the following:
- Matched related HSCT
- Mismatched related HSCT
- For patients who have received a transplant, occurrence of one of the following > 30 days post-HSCT:
- Minimal residual disease (MRD) positive at > 1 copy per 1 x 10,000 reference copies post-HSCT
- Decreasing donor chimerism detected on two bone marrow biopsies or peripheral blood analyses at a > 7-day interval
- Recurrent disease
- Life expectancy >10 weeks;
- Signed donor and patient/guardian informed consent;
- For mismatched related donor recipients, a minimum genotypic identical match of 5/10 is required, as determined by high resolution typing, at least one allele of each of the following genetic loci must be matched: HLA-A, HLA-B, HLA-C, HLA- DRB1, and HLA-DQB1.
- Performance status: Karnofsky/Lansky score > 70%.
- Adequate organ function as measured by:
- High-risk Acute Leukemia (Acute lymphoblastic leukemia [ALL] or acute myeloid leukemia [AML]) in any CR
- High-risk Acute Leukemia (Acute lymphoblastic leukemia [ALL] or acute myeloid leukemia [AML]) in any CR
- Hepatic: direct bilirubin ≤ 3x ULN, or AST/ALT ≤ 5x ULN.
- Bone marrow;
- > 25% donor T cell chimerism
- ANC >1 x 10^9/L.
- Cardiac: LVEF at rest >45%.
- Pulmonary: FEV 1, FVC, DLCO (diffusion capacity for CO) > 50% predicted (corrected for hemoglobin); for children who are unable to perform pulmonary function tests due to age or developmental ability, there must be no evidence of dyspnea or no need for supplemental oxygen as evidenced by 02 saturation ≥ 92% on room air.
- Hepatic: direct bilirubin ≤ 3x ULN, or AST/ALT ≤ 5x ULN.
- Renal: creatinine clearance ≤ 2x of ULN for age
Who cannot join
- ≥ Grade II acute GVHD or moderate to severe chronic GVHD due to a previous allograft at the time of screening;
- Active CNS involvement by malignant cells (< 2 months prior to time of consent);
- Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
- Positive HIV serology or viral RNA;
- Pregnancy (positive serum βHCG test) or breast-feeding female;
- Patients of reproductive age unwilling to use effective forms of birth control or abstinence for a year after BPX-501 T cell infusion.
Trial locations and contacts
3 sites in 1 country.
Italy3 sites
San Matteo Hospital
Pavia, 27100
IRCCS Ospedale Pediatrico Bambino Gesù
Rome, 00161
Ospedale Infantile Regina Margherita
Turin, 10126
About this study
Official title: A Phase I Study Of Safety, Pharmacokinetics, And Efficacy Of Donor BPX-501 Cells and Rimiducid Infusion For Children With Recurrent Hematologic Malignancies or Minimal Residual Disease After Allogeneic Transplant
Phase I, open-label, non-randomized study of safety, pharmacokinetics and efficacy of donor BPX-501 T cell infusion in children with recurrent or minimal residual disease (MRD) hematologic malignancies post-allogeneic transplant. The study will consist of the Main Study and an optional Pharmacokinetics (PK) Sub-Study.
Read the detailed description
Main Study:
Approximately 16 subjects will participate in the BPX-501 main study. The treatment consists of three courses of BPX-501 T cell infusions at 30 day intervals with 2 escalating dose levels (DL). DL1 on Day 0; DL2 on Days 30 and 60.
Two doses of rimiducid (AP1903) will be investigated for the treatment of aGvHD after BPX-501 T cell infusion. A 0.1mg/kg initial dose of rimiducid which has demonstrated the ability to induce >50% BPX-501 T cell eradication in preclinical animal models will first be administered in the event of uncontrollable aGvHD. If there is no response to this dose within 24hrs + 12hrs a second dose of 0.4 mg/kg (which has been reported to induce T cell eradication of > 90%) will be administered. If there is no measurable GvHD response to the initial dose of 0.1 mg/kg rimiducid in 2 subjects, the starting dose of rimiducid will be 0.4 mg/kg for all subsequent subjects.
Rimiducid (AP1903) Optional PK Sub-Study:
Approximately 12 subjects will be recruited to participate in the optional Rimiducid (AP1903) PK sub-study. Subjects will be assigned to one of two arms and receive either 0.04mg/kg or 0.4mg/kg of Rimiducid (AP1903). Each arm will have a target enrollment of 6 subjects.
- Arm 1: 0.04mg/kg Rimiducid (AP1903), 6 subjects;
- Arm 2: 0.4mg/kg Rimiducid (AP1903), 6 subjects. Rimiducid PK samples and ECG data will be collected at Pre-dose (0 hour), 30 minutes, 2 hours and 8 hours following the initiation of rimiducid (AP1903) infusion.
Efforts shall be made to enroll at least one subject from each age subset into the PK sub-study: infants and toddlers (12 months to 23 months); children (2-11 years); and adolescents (12-18 years).
- Conditions
- Hematologic Malignancy
- Being tested
- BPX-501 T cells, rimiducid
- Keywords
- leukemia, myelodysplastic syndrome, lymphoma, minimal residual disease, BPX-501, AP1903, rimiducid
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Myelodysplastic Syndromes, Lymphoma, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BPX-501 T cellsBiological
Also called rivogenlecleucel
Biological: T cells transduced with CaspaCIDe® safety switch
rimiducidDrug
Also called AP1903
administered to eliminate BPX-501 cells in the event of GVHD
| Study group | Role | What they receive |
|---|---|---|
| BPX-501 T cells and rimiducid | Experimental | All subjects will receive 3 courses of BPX-501 T cell infusions at escalating dose levels (DL). DL1 on Day 0, DL2 on Days 30 and 60. The first dose of BPX-501 T cells will occur ≥30 days after hematopoietic stem cell transplant (HSCT).
Two doses of AP1903 ( 0.1 mg/kg and 0.4 mg/kg) will be investigated for the treatment of aGvHD after BPX-501 T cell infusion. Receives: Biological: BPX-501 T cells; Drug: rimiducid |
What is being measured
The primary outcome is the main question the study is designed to answer.
BPX-501 Safety
Incidence of treatment emergent adverse events of 2 stratified dose levels of BPX-501 T cell infusions based on patient-donor match in pediatric subjects with hematologic malignancies
Measured: Month 24
Mean plasma concentration
Measure plasma concentrations of rimiducid (AP1903) at two doses (Arm 1: 0.04mg/kg; Arm 2: 0.4mg/kg) in pediatric subjects, during and after a 2-hour infusion
Measured: pre-dose, 30 min, 2 hours and 8 hours after start of infusion
Secondary outcomes (2)
Overall survival
Measure overall survival rates after BPX-501 infusion
Measured: Month 24
Response Rate
Assess response rates after BPX-501 infusion
Measured: Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2018
- Study start1 Feb 2018
- Primary completionSep 2022 (estimated)
- Study completionSep 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic MalignancyStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bellicum Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bellicum Pharmaceuticals, Study director, Bellicum Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03459170
- Sponsor's protocol ID
- BP-I-008
- Status last verified
- Jul 2022
- First submitted
- 23 Feb 2018
- Last updated
- 12 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Of Safety, Pharmacokinetics, And Efficacy Of Donor BPX-501 Cells and Rimiducid Infusion For Children With Recurrent Hematologic Malignancies or Minimal Residual Disease After Allogeneic Transplant
- ClinicalTrials.gov ID
- NCT03459170
- Acronym / sponsor ID
- BP-I-008
- Conditions
- Hematologic Malignancy
- Keywords
- leukemia, myelodysplastic syndrome, lymphoma, minimal residual disease, BPX-501, AP1903, rimiducid
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Bellicum PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- Sep 2022 (estimated)
- Study completion
- Sep 2035 (estimated)
- First posted
- 8 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase I, open-label, non-randomized study of safety, pharmacokinetics and efficacy of donor BPX-501 T cell infusion in children with recurrent or minimal residual disease (MRD) hematologic malignancies post-allogeneic transplant. The study will consist of the Main Study and an optional Pharmacokinetics (PK) Sub-Study.
Detailed description
Main Study:
Approximately 16 subjects will participate in the BPX-501 main study. The treatment consists of three courses of BPX-501 T cell infusions at 30 day intervals with 2 escalating dose levels (DL). DL1 on Day 0; DL2 on Days 30 and 60.
Two doses of rimiducid (AP1903) will be investigated for the treatment of aGvHD after BPX-501 T cell infusion. A 0.1mg/kg initial dose of rimiducid which has demonstrated the ability to induce >50% BPX-501 T cell eradication in preclinical animal models will first be administered in the event of uncontrollable aGvHD. If there is no response to this dose within 24hrs + 12hrs a second dose of 0.4 mg/kg (which has been reported to induce T cell eradication of > 90%) will be administered. If there is no measurable GvHD response to the initial dose of 0.1 mg/kg rimiducid in 2 subjects, the starting dose of rimiducid will be 0.4 mg/kg for all subsequent subjects.
Rimiducid (AP1903) Optional PK Sub-Study:
Approximately 12 subjects will be recruited to participate in the optional Rimiducid (AP1903) PK sub-study. Subjects will be assigned to one of two arms and receive either 0.04mg/kg or 0.4mg/kg of Rimiducid (AP1903). Each arm will have a target enrollment of 6 subjects.
- Arm 1: 0.04mg/kg Rimiducid (AP1903), 6 subjects;
- Arm 2: 0.4mg/kg Rimiducid (AP1903), 6 subjects. Rimiducid PK samples and ECG data will be collected at Pre-dose (0 hour), 30 minutes, 2 hours and 8 hours following the initiation of rimiducid (AP1903) infusion.
Efforts shall be made to enroll at least one subject from each age subset into the PK sub-study: infants and toddlers (12 months to 23 months); children (2-11 years); and adolescents (12-18 years).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BPX-501 T cells and rimiducid | Experimental | Biological: BPX-501 T cells, Drug: rimiducidAll subjects will receive 3 courses of BPX-501 T cell infusions at escalating dose levels (DL). DL1 on Day 0, DL2 on Days 30 and 60. The first dose of BPX-501 T cells will occur ≥30 days after hematopoietic stem cell transplant (HSCT). Two doses of AP1903 ( 0.1 mg/kg and 0.4 mg/kg) will be investigated for the treatment of aGvHD after BPX-501 T cell infusion. |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (32 listed)
- Patients aged < 18
- Clinical diagnosis of one of the following pediatric hematological malignancies:
- Planned or previous treatment of hematological malignancy with one of the following:
- For patients who have received a transplant, occurrence of one of the following > 30 days post-HSCT:
- Life expectancy >10 weeks;
Key exclusion criteria (6 listed)
- ≥ Grade II acute GVHD or moderate to severe chronic GVHD due to a previous allograft at the time of screening;
- Active CNS involvement by malignant cells (< 2 months prior to time of consent);
- Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
- Positive HIV serology or viral RNA;
- Pregnancy (positive serum βHCG test) or breast-feeding female;
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-501 T cellsAlso: rivogenlecleucelBiological: T cells transduced with CaspaCIDe® safety switch | Biological | BPX-501 T cells and rimiducid |
| rimiducidAlso: AP1903administered to eliminate BPX-501 cells in the event of GVHD | Drug | BPX-501 T cells and rimiducid |
Primary outcome
BPX-501 Safety
Time frame: Month 24
Incidence of treatment emergent adverse events of 2 stratified dose levels of BPX-501 T cell infusions based on patient-donor match in pediatric subjects with hematologic malignancies
Mean plasma concentration
Time frame: pre-dose, 30 min, 2 hours and 8 hours after start of infusion
Measure plasma concentrations of rimiducid (AP1903) at two doses (Arm 1: 0.04mg/kg; Arm 2: 0.4mg/kg) in pediatric subjects, during and after a 2-hour infusion
2 secondary outcomes
Overall survival
Time frame: Month 24
Response Rate
Time frame: Month 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2022.
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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.
Bellicum Pharmaceuticals 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 study testing BPX-501 T cells and rimiducid in people with Hematologic Malignancy, run by Bellicum Pharmaceuticals at 3 sites in Italy.
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 32 inclusion and 6 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: under way, not looking for participants, as of the sponsor's last update on 12 Jul 2022. 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 Italy. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
BPX-501 Safety (time frame: Month 24). 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 12 Jul 2022.