Safety Study of Gene Modified Donor T-cells Following Partially Mismatched Stem Cell Transplant
Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia, Lymphoma
About this trial
This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring iCaspase9, iCasp9, Inducible Caspase, AP1903, Dimerizer drug, T depleted, Suicide gene, CD-34 selection, haplotransplantation, Graft versus host disease, Allogenic transplantation
Eligibility Criteria
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.
Sites / Locations
- Emory University Winship Cancer Institute
- Roswell Park Cancer Institute
- Memorial Sloan Kettering Cancer Center
- University Hospitals of Cleveland
- Oregon Health & Science University
- Baylor Sammons Cancer Center
- UT Southwestern Medical Center
- Fred Hutchinson Cancer Research Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
SCT, BPX-501 dose 1, Rimiducid if needed
SCT, BPX-501 dose 2, Rimiducid if needed
SCT, BPX-501 dose 3, Rimiducid if needed
SCT, BPX-501 dose 4, 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.
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.
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.
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.