- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03459170
Safety/PK Study of Gene Modified Donor T Cell Infusion in Children With Recurrent Hem Malignancies After Allo Transplant
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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
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-
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Pavia, Italy, 27100
- San Matteo Hospital
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Rome, Italy, 00161
- IRCCS Ospedale Pediatrico Bambino Gesu
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Turin, Italy, 10126
- Ospedale Infantile Regina Margherita
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
≥ 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BPX-501 T cells and rimiducid
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. |
Biological: T cells transduced with CaspaCIDe® safety switch
Other Names:
administered to eliminate BPX-501 cells in the event of GVHD
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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Month 24
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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
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pre-dose, 30 min, 2 hours and 8 hours after start of infusion
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: Month 24
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Measure overall survival rates after BPX-501 infusion
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Month 24
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Response Rate
Time Frame: Month 24
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Assess response rates after BPX-501 infusion
|
Month 24
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BP-I-008
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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