Acute Myeloid Leukemia, Myelodysplastic Syndromes
Conditions
Brief summary
This study compares the safety and effectiveness of giving rivogenlecleucel (BPX-501 T cells) to patients with AML or MDS post haploidentical hematopoietic stem cell transplant compared to post-transplant cyclophosphamide.
Detailed description
In the Phase 2 portion, participants will undergo αβ T cell and CD19+ B cell depleted haploidentical HSCT followed by an infusion of a fixed dose of rivogenlecleucel (BPX-501 T cells) per kg. These participants will be evaluated for prespecified dose limiting toxicities (DLTs) for a 100-day dose limiting toxicity window. Following completion of the Phase 2 portion, participants will be enrolled and randomized to one of two treatment arms in the Phase 3 portion. * Arm A:αβ T-cell and CD19+ B-cell-depleted haplo-HSCT plus treatment with rivogenlecleucel * Arm B: haplo-HSCT plus post transplant cyclophosphamide Pediatric patients ages 12-17 will also be included in US only.
Interventions
BIOLOGICALrivogenlecleucel
Biological: T cells transduced with caspase 9 safety switch
DRUGrimiducid
administered to inactivate rivogenlecleucel in the event of GVHD
DRUGCyclophosphamide
GVHD prophylaxis
PROCEDUREhaplo-HSCT
treatment for disease
Sponsors
Bellicum Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Signed informed consent Meeting institutional criteria to undergo allogenic HSCT Age 18-70 y/o (12-70 y/o in US only) Patients with AML or MDS as defined below: AML Patients Patients with intermediate to adverse AML as defined by ELN (Dohner, 2017). * AML in first complete remission (CR1) with high-risk features defined as \> 1 cycle of induction therapy required to achieve remission OR preceding MDS or myeloproliferative disease * AML in CR1 with intermediate-risk features * AML in second or subsequent complete response * AML with myelodysplasia-related changes (AML-MRC) * Therapy related AML in first or subsequent complete remission * De novo AML in second or subsequent complete remission MDS Patients * High or very-high risk MDS by IPSS-R classification * Intermediate risk or higher MDS patients who failed a hypomethylating agent Lack of suitable conventional donor (i.e. HLA 10/10 related or unrelated donor) At least a 5/10 genotypic identical haplotype match The donor and recipient must be identical, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 Patients with adequate organ function Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
Exclusion criteria
* HLA 10/10 allele matched (HLA-A,-B,-C,-DRBl, and DQB1) related donor or unrelated donor * Autologous hematopoietic stem cell transplant ≤ 3 months before enrollment * Prior allogeneic transplantation * Active CNS involvement by malignant cells (less than 2 months from the conditioning) * Current uncontrolled clinically active bacterial, viral or fungal infection * Positive HIV serology or viral RNA * Pregnancy (positive serum or urine βHCG test) or breast-feeding * Fertile men or women unwilling to use effective forms of birth control or abstinence for a year after transplantation * Radiographic, histologic, or known history of cirrhosis * Overlapping MDS and myeloproliferative neoplasms (MPN) disease * Patients with acute promyelocytic leukemia (APL) * Known hypersensitivity to dimethyl sulfoxide (DMSO)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Experiencing 3 or More Dose Limiting Toxicities [Phase 2] Within a 100-day DLT Window After Receiving BPX-501 | 100 days | If any of the following adverse events that occur within the DLT window they will be considered a DLT: * Grade III or IV acute GVHD attributable to rivogenlecleucel and non-responsive to \> 1 dose of rimiducid treatment (plus standard doses (at least 1 mg/kg) of methylprednisone or dose equivalent of other corticosteroids, and/or calcineurin inhibitor) within 14 days * Grade 3-4 neurologic events attributable to rivogenlecleucel * Death due to any cause other than underlying disease * Any CTCAE Grade 3-5 adverse events related to rivogenlecleucel (including allergic reactions, infusion reactions, and any other related adverse reactions whether expected or unexpected). in case 3 or more DLTs are observed with 3 x 10E6 dose, another cohort would have been enrolled to receive the 1 x 10E6 cell dose (never happened as study terminated early) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase II, Cohort 1 αβ T-cell and CD19+ B-cell-depleted haploidentical stem cell transplantation plus rivogenlecleucel
Rimiducid will be administered to inactivate rivogenlecleucel in the event of GVHD not responsive to standard of care treatment
rivogenlecleucel: Biological: T cells transduced with caspase 9 safety switch
rimiducid: administered to inactivate rivogenlecleucel in the event of GVHD
haplo-HSCT: treatment for disease | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Phase II, Cohort 1 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 28 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| history of AML in the second or subsequent complete remission | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Number of Subjects Experiencing 3 or More Dose Limiting Toxicities [Phase 2] Within a 100-day DLT Window After Receiving BPX-501
If any of the following adverse events that occur within the DLT window they will be considered a DLT: * Grade III or IV acute GVHD attributable to rivogenlecleucel and non-responsive to \> 1 dose of rimiducid treatment (plus standard doses (at least 1 mg/kg) of methylprednisone or dose equivalent of other corticosteroids, and/or calcineurin inhibitor) within 14 days * Grade 3-4 neurologic events attributable to rivogenlecleucel * Death due to any cause other than underlying disease * Any CTCAE Grade 3-5 adverse events related to rivogenlecleucel (including allergic reactions, infusion reactions, and any other related adverse reactions whether expected or unexpected). in case 3 or more DLTs are observed with 3 x 10E6 dose, another cohort would have been enrolled to receive the 1 x 10E6 cell dose (never happened as study terminated early)
Time frame: 100 days
Population: Study terminated early after graft failure of the first participant.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase II, Cohort 1 | Number of Subjects Experiencing 3 or More Dose Limiting Toxicities [Phase 2] Within a 100-day DLT Window After Receiving BPX-501 | 1 Participants |