Acute Myeloid LeukemiaPhase 2/3THRIVENCT03699475
Study of Haplo-HSCT + Rivogenlecleucel vs Haplo-HSCT + Post Transplant Cyclophosphamide in Patients With AML or MDS
A Phase 2/3 study testing rivogenlecleucel, rimiducid and Cyclophosphamide in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Bellicum Pharmaceuticals at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 70 years
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- What is being tested?
- rivogenlecleucel, rimiducid and Cyclophosphamide
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 2 sitesUnited States
- Study dates
- 27 Dec 2018to 23 Jul 2019
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 12 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
TriStar Bone Marrow Transplant, LLC
Nashville, Tennessee, 37203
Methodist Healthcare System of San Antonio Clinical Trials Office
San Antonio, Texas, 78229
About this study
Official title: A Randomized Phase II/III Study of αβ T Cell-Depleted, Related, Haploidentical Hematopoietic Stem Cell Transplant (Haplo-HSCT) Plus Rivogenlecleucel vs. Haplo-HSCT Plus Post-Transplant Cyclophosphamide (PTCy) in Patients With AML or MDS
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.
Read the 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.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Being tested
- rivogenlecleucel, rimiducid, Cyclophosphamide, haplo-HSCT
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rivogenlecleucelBiological
Also called BPX-501 T cells
Biological: T cells transduced with caspase 9 safety switch
rimiducidDrug
Also called AP1903
administered to inactivate rivogenlecleucel in the event of GVHD
CyclophosphamideDrug
Also called Cytoxan
GVHD prophylaxis
haplo-HSCTProcedure or surgery
treatment for disease
| Study group | Role | What they receive |
|---|---|---|
| single-arm Phase II: 3 x 10E6 BPX-501 cell/kg | Experimental | Determining the safety of maximum allowable Dose for BPX-501 starting at 3 x 10E6 cells/kg
Rimiducid will be administered to inactivate rivogenlecleucel in the event of GVHD not responsive to standard of care treatment Receives: Biological: rivogenlecleucel; Drug: rimiducid; Procedure: haplo-HSCT |
| phase 3 Arm A: Dose Determined in phase 2 group (never completed) | Experimental | αβ T cell and CD19+ B cell-depleted, related haploidentical hematopoietic stem cell transplantation (haplo-HSCT) plus rivogenlecleucel Receives: Biological: rivogenlecleucel; Drug: rimiducid; Procedure: haplo-HSCT |
| phase 3 Arm B: dose determined in the phase 2 group (never completed) | Active comparator | haplo-HSCT followed by post-transplant cyclophosphamide (PTCy) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) Receives: Drug: Cyclophosphamide; Procedure: haplo-HSCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2018
- Study start27 Dec 2018
- Primary completion23 Jul 2019
- Study completion23 Jul 2019
Why it stopped: Funding, portfolio re-prioritization
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid LeukemiaStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
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
- NCT03699475
- Sponsor's protocol ID
- BPX501-301A
- Acronym
- THRIVE
- Status last verified
- Sep 2023
- First submitted
- 5 Oct 2018
- Last updated
- 29 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II/III Study of αβ T Cell-Depleted, Related, Haploidentical Hematopoietic Stem Cell Transplant (Haplo-HSCT) Plus Rivogenlecleucel vs. Haplo-HSCT Plus Post-Transplant Cyclophosphamide (PTCy) in Patients With AML or MDS
- ClinicalTrials.gov ID
- NCT03699475
- Acronym / sponsor ID
- THRIVE / BPX501-301A
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding, portfolio re-prioritization
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Bellicum PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 27 Dec 2018 (actual)
- Primary completion
- 23 Jul 2019 (actual)
- Study completion
- 23 Jul 2019 (actual)
- First posted
- 9 Oct 2018 (actual)
- Results
- Posted 1 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| single-arm Phase II: 3 x 10E6 BPX-501 cell/kg | Experimental | Biological: rivogenlecleucel, Drug: rimiducid, Procedure: haplo-HSCTDetermining the safety of maximum allowable Dose for BPX-501 starting at 3 x 10E6 cells/kg Rimiducid will be administered to inactivate rivogenlecleucel in the event of GVHD not responsive to standard of care treatment |
| phase 3 Arm A: Dose Determined in phase 2 group (never completed) | Experimental | Biological: rivogenlecleucel, Drug: rimiducid, Procedure: haplo-HSCTαβ T cell and CD19+ B cell-depleted, related haploidentical hematopoietic stem cell transplantation (haplo-HSCT) plus rivogenlecleucel |
| phase 3 Arm B: dose determined in the phase 2 group (never completed) | Active comparator | Drug: Cyclophosphamide, Procedure: haplo-HSCThaplo-HSCT followed by post-transplant cyclophosphamide (PTCy) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) |
Who may qualify
- Ages
- 12 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Signed informed consent
- Meeting institutional criteria to undergo allogenic HSCT
- Age 18-70 y/o (12-70 y/o in US only)
- 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
Key exclusion criteria (12 listed)
- 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
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 |
|---|---|---|
| rivogenlecleucelAlso: BPX-501 T cellsBiological: T cells transduced with caspase 9 safety switch | Biological | phase 3 Arm A: Dose Determined in phase 2 group (never completed), single-arm Phase II: 3 x 10E6 BPX-501 cell/kg |
| rimiducidAlso: AP1903administered to inactivate rivogenlecleucel in the event of GVHD | Drug | phase 3 Arm A: Dose Determined in phase 2 group (never completed), single-arm Phase II: 3 x 10E6 BPX-501 cell/kg |
| CyclophosphamideAlso: CytoxanGVHD prophylaxis | Drug | phase 3 Arm B: dose determined in the phase 2 group (never completed) |
| haplo-HSCTtreatment for disease | Procedure or surgery | phase 3 Arm A: Dose Determined in phase 2 group (never completed), phase 3 Arm B: dose determined in the phase 2 group (never completed), single-arm Phase II: 3 x 10E6 BPX-501 cell/kg |
Primary outcome
Number of Subjects Experiencing 3 or More Dose Limiting Toxicities [Phase 2] Within a 100-day DLT Window After Receiving BPX-501
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing rivogenlecleucel, rimiducid and Cyclophosphamide in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Bellicum Pharmaceuticals at 2 sites in United States.
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 19 inclusion and 12 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: stopped early, as of the sponsor's last update on 29 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Subjects Experiencing 3 or More Dose Limiting Toxicities [Phase 2] Within a 100-day DLT Window After Receiving BPX-501 (time frame: 100 days). 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 29 Sep 2023.