- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01744223
Safety Study of Gene Modified Donor T-cells Following Partially Mismatched Stem Cell Transplant
A Phase 1/2 Dose Escalation Study Evaluating Safety and Feasibility of BPX-501 T Cells After Partially Mismatched, Related, T Cell-Depleted HSCT (Hematopoietic Stem Cell Transplant)
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Expanded Access
Contacts and Locations
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Emory University Winship Cancer Institute
-
-
New York
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Buffalo, New York, United States, 14263
- Roswell Park Cancer Institute
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New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
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-
Ohio
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Cleveland, Ohio, United States, 44106
- University Hospitals of Cleveland
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-
Oregon
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Portland, Oregon, United States, 97239
- Oregon Health & Science University
-
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Texas
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Dallas, Texas, United States, 75390
- UT Southwestern Medical Center
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Dallas, Texas, United States, 75246
- Baylor Sammons Cancer Center
-
-
Washington
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Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Signed informed consent
- Age ≥ 18 years and ≤ 65 years
- Deemed eligible for allogeneic stem cell transplantation
- Lack of suitable conventional donor (i.e. 8/8 related or unrelated donor) or presence of rapidly progressive disease not permitting time to identify an unrelated donor
HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, and DRBl, and loci
- A minimum genotypic identical match of 4/8 is required.
- The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, and HLA-DRB1
Subjects with adequate organ functions as measured by:
- Cardiac: Left ventricular ejection fraction at rest must be ≥ 45%
- Hepatic: Bilirubin ≤ 2.5 mg/dL and ALT, AST and Alkaline Phosphatase < 5 x ULN
- Renal: Serum creatinine within normal range for age or creatinine clearance, or with a recommended GFR ≥ 50 mL/min/1.73m2
- Pulmonary: FEV 1, FVC and DLCO (diffusion capacity) ≥ 50% predicted (corrected for hemoglobin); or O2 saturation > 92% on room air
Clinical diagnosis of one of the following:
a. Acute Leukemia (includes T lymphoblastic lymphoma) in 2nd or subsequent complete remission (CR) i. Acute Lymphoblastic Leukemia (ALL) in 2nd or subsequent CR. ALL shall be morphologic remission at the time of transplant. Morphologic remission is defined that subjects with normal neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and no extramedullary disease ii. Acute Myeloid Leukemia (AML) in 2nd or subsequent CR with or without persistent minimal residual disease b. High-risk ALL in 1st CR (including features such as those in i-iii) i. Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), MLL rearrangements ii. Subjects over 30 years of age, or iii. Time to complete remission was greater than 4 weeks. c. High-risk AML in 1st CR (including features such as those listed in i-vii) i. Greater than 1 cycle of induction therapy required to achieve remission ii. Preceding myelodysplastic syndrome (MDS) iii. Presence of FLT3 abnormalities iv. FAB M6 or M7 leukemia v. Adverse cytogenetics for overall survival such as those associated with MDS vi. Complex karyotype (>3 abnormalities), or vii. Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)], t(l1;19)(q23;p13.1) d. High risk Myelodysplastic Syndrome e. Non-Hodgkin's Lymphoma relapsed after autologous transplantation f. Non-Hodgkin's Lymphoma with insufficient autologous hematopoietic stem cells to undergo autologous transplantation g. CML i. in first chronic phase that has not attained at least a complete cytogenetic remission after exposure to at least 3 tyrosine kinase inhibitors ii. in accelerated phase that has not attained at least a complete cytogenetic remission iii. in second chronic phase
- Performance status: Karnofsky score ≥60%.
- Patient with hematologic malignancy not responding to /or not eligible for conventional therapy and are approved by Sponsor
Exclusion Criteria:
- HLA 8/8 allele matched (HLA-A,-B,-Cw,-DRBl) related or unrelated donor able to donate.
- Autologous hematopoietic stem cell transplant < 3 months prior to enrollment.
- Pregnancy or breast-feeding.
- Evidence of HIV infection or known HIV positive serology.
- Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings). The treating physician will make final determination.
- Non-hematologic malignancy within prior three (3) years, with the exception of squamous cell or basal cell skin carcinoma.
- Prior allogeneic hematopoietic stem cell transplant.
- Subjects with a history of primary idiopathic myelofibrosis.
- Bovine product allergy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: SCT, BPX-501 dose 1, Rimiducid if needed
2x10E5 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid. |
Subjects will receive 2x10E5 donor T cells/kg genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene (BPX-501) after stem cell transplant.
Other Names:
Dimerizer drug administered by intravenous infusion in those subjects who develop GVHD after infusion of BPX-501 cells.
Other Names:
all subjects will receive an alpha beta depleted donor transplant as part of treatment
|
Experimental: SCT, BPX-501 dose 2, Rimiducid if needed
5x10E5 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid. |
Dimerizer drug administered by intravenous infusion in those subjects who develop GVHD after infusion of BPX-501 cells.
Other Names:
all subjects will receive an alpha beta depleted donor transplant as part of treatment
Subjects will receive 5x10E5 donor T cells/kg genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene (BPX-501) after stem cell transplant.
Other Names:
|
Experimental: SCT, BPX-501 dose 3, Rimiducid if needed
1x10E6 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid. |
Dimerizer drug administered by intravenous infusion in those subjects who develop GVHD after infusion of BPX-501 cells.
Other Names:
all subjects will receive an alpha beta depleted donor transplant as part of treatment
Subjects will receive 1x10E6 donor T cells/kg genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene (BPX-501) after stem cell transplant.
Other Names:
|
Experimental: SCT, BPX-501 dose 4, Rimiducid if needed
3x10E6 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant . Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid. |
Dimerizer drug administered by intravenous infusion in those subjects who develop GVHD after infusion of BPX-501 cells.
Other Names:
all subjects will receive an alpha beta depleted donor transplant as part of treatment
Subjects will receive 3x10E6 donor T cells/kg genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene (BPX-501) after stem cell transplant.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
BPX-501 Safety
Time Frame: 24 months
|
To evaluate the safety of infusion of each of 4 dose cohorts of BPX-501 (2x105, 5x105, 1x106 and 3x106 cells/kg) after transplantation of partially mismatched T cell depleted hematopoietic stem cell transplant (HSCT)
|
24 months
|
Rimiducid Safety
Time Frame: 24 months
|
To evaluate the safety of the infusion of the rimiducid in subjects who received BPX-501 and have developed visceral or steroid refractory graft-versus-host-disease
|
24 months
|
MTD
Time Frame: 24 months
|
To determine the maximum dose of BPX-501 (up to 3x106 cells/kg) that results in an adjusted cumulative incidence by Day 100 of no more than 45% Grade II - IV aGVHD and / or no more than 17% Grade III -IV aGVHD.
|
24 months
|
Immune Reconstitution
Time Frame: 24 months
|
To assess immune reconstitution for each dose cohort
|
24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy- NRM
Time Frame: 100, 180 days and 1 year
|
Non-Relapse Mortality (NRM)
|
100, 180 days and 1 year
|
Efficacy- DFS
Time Frame: 24 months
|
Disease-free survival
|
24 months
|
Efficacy- TRM
Time Frame: 24 months
|
Transplant related mortality (TRM)
|
24 months
|
Efficacy- Relapse
Time Frame: 24 months
|
Incidence of Relapse
|
24 months
|
Incidence of engraftment
Time Frame: 24 months
|
Evaluation of neutrophil and platelet engraftment, kinetics of donor cell engraftment and graft failure
|
24 months
|
GvHD
Time Frame: 24 months
|
Incidence and severity of acute and chronic GvHD
|
24 months
|
GvHD post Rimiducid Administration
Time Frame: 24 months
|
Time to resolution of acute GvHD after administration of Rimiducid
|
24 months
|
BPX-501 Safety Profile
Time Frame: 24 months
|
Characterize the safety profile of BPX-501 including evaluation of high grade toxicity and infectious complications
|
24 months
|
Pharmacokinetics of Rimiducid
Time Frame: 24 months
|
Pharmacokinetic disposition of Rimiducid
|
24 months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
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
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Bone Marrow Diseases
- Hematologic Diseases
- Leukemia, Lymphoid
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
Other Study ID Numbers
- BP-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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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