Allogeneic, CAR-T, Protein Sequestration, Non-gene EditedPhase 1NCT05576181
Safety and Efficacy of ThisCART19A Bridging Hematopoietic Stem Cell Transplantation in Patients With Refractory or Relapsed B-cell Acute Lymphoblastic Leukemia
A Phase 1 study testing ThisCART19A, Fludarabine Oral Tablet and Cyclophosphamide in people with Allogeneic, CAR-T, Protein Sequestration, Non-gene Edited, run by Fundamenta Therapeutics, Ltd..
Trial summary
This is a a phase 1, open label study to assess the safety and efficacy of ThisCART19 (Allogeneic CAR-T targeting CD19) Bridging Hematopoietic Stem Cell Transplantation in patients with refractory or relapsed B cell acute lymphoblastic leukemia (r/r B-ALL). Read more about this study
- Who is it for?
- Ages 14 to 75 years
- Conditions the study is for
- Allogeneic, CAR-T, Protein Sequestration, Non-gene Edited
- What is being tested?
- ThisCART19A, Fludarabine Oral Tablet and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- No sites listed yet
- Study dates
- 15 Oct 2022to 22 Jul 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 14 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All subjects or legal representatives must sign a voluntary letter of consent approved by the IRB in person prior to the commencement of any screening procedure;
- Patients diagnosed with B-ALL;
- No gender limitation, Age 14 years to 75 years (both upper and lower limits included);
- Consistent with the diagnosis of recurrent refractory B-ALL. Recurrence： was defined as the recurrence of lymphoblasts（≥5%） in peripheral blood or bone marrow or extramedullary diseasefor patients who had acquired CR ; Refractory ：was defined as failure to CR or CRi at the end of induction therapy (generally referred to 4-week regimen or Hyper-CVAD regimen);Patients with Ph+ R/R ALL who failed after 2-line TKI treatment, were intolerant to TKI treatment or were not suitable for TKI treatment; The following factors can coexist:
- Failure to prepare autologous CAR-T (definition: too few autologous lymphocytes [200/ML] or cannot meet the release standard);
- Experienced treatment with auto car-T/berintoomumab/ CD22 antibody conjugation drugs;
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- ≥100 days after hematopoietic stem cell transplantation;
- High-risk patients (High risk was defined as a high white blood cell count ≥30×109/L at diagnosis or with poor cytogenetic prognosis);
- Hypodiploid (<44 chromosomes);
- KMT2A rearrangement: t (4;11) or otherwise;
- t (v; 14q32) /IgH
- t (9; 22) (q34; q11.2) or BCR-ABL1
- Complex karyotype (≥5 chromosomal abnormalities);
- BCR-ABL1-like (Ph-like) ALL;
- JAK-STAT (CRLF2r, EPORr, JAK1/2/3r, TYK2r, mutations of SH2B3, IL7r, Jak1/2/3);
- ABL class rearrangements (such as ABL1, ABL2, PDGFRA, PDGFRB, FGFR, etc.)
- Others (NTRKr, FLT3r, LYNr, PTK2Br);
- Intrachromosomal amplification of chromosome 21 (iAMP21);
- t (17; 19): TCF3-HLF fusion;
- Alterations of IKZF1;
- Extramedullary lesions.
- The expected survival time is ≥12 weeks;
- ECOG score 0-2;
- Adequate bone marrow, renal, hepatic, pulmonary and cardiac function;
- CD19 was still expressed in leukemia cells in bone marrow, peripheral blood or biopsy tissue by flow cytometry within one month prior to informed consent (after the last treatment).
Who cannot join
- Allergic to preconditioning measures;
- Diagnosis of chronic myelogenous leukemia lymphoid blast crisis;
- Isolated extramedullary relapse;
- Presence of CNS-3 disease or CNS-2 disease with neurological changes;
- Imaging confirmed the presence of central nervous system involvement;
- Severe CNS disorders such as a history of frequent epileptic seizures;
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- Patients with other malignancies other than B-cell malignancies within 5 years prior to screening. Patients with cured skin squamous carcinoma, basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited.
- Uncontrollable bacterial, fungal and viral infection during screening;
- Patients had pulmonary embolism (PE) and/or deep vein thrombosis (DVT) within 3 months prior to enrollment;
- Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment;
- Radiation therapy within 2 weeks prior to lymphodepletion chemotherapy (>30% bone marrow exposure);
- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) or Syphilis infection. HBV-DNA < 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenofovir, etc, and supervisory the relative indication during the treatment;
- Vaccinated with influenza vaccine within 2 weeks prior to lymphodepleting chemotherapy (Severe Acute Respiratory Syndrome-Corona virus disease 19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included) ;
- Patients who are receiving Graft versus host disease Hepatitis(GvHD) treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion;
- Women who are in pregnant or lactating, and female subjects or partners who plan to be pregnant within 1 year after cell infusion. Male subjects who plan pregnancy within 1 year after infusion;
- Any ineligibility conditions considered by the investigator that may increase the risk of the subject or interfere with the results of the study.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Single Dose-escalation Study to Evaluate the Safety and Efficacy of Allogeneic CAR-T Targeting CD19 Bridging Hematopoietic Stem Cell Transplantation in Patients With Refractory or Relapsed B Cell Acute Lymphoblastic Leukemia
This is a a phase 1, open label study to assess the safety and efficacy of ThisCART19 (Allogeneic CAR-T targeting CD19) Bridging Hematopoietic Stem Cell Transplantation in patients with refractory or relapsed B cell acute lymphoblastic leukemia (r/r B-ALL).
Read the detailed description
This is a phase 1, single-center, nonrandomized, open-label, dose-escalation study to evaluate the safety and efficacy of ThisCART19A Bridging Hematopoietic Stem Cell Transplantation in patients with CD19 positive r/r B-ALL and identify a treatment regimen most likely to result in clinical efficacy while maintaining a favorable safety profile.
- Being tested
- ThisCART19A, Fludarabine Oral Tablet, Cyclophosphamide, VP-16, HSCT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThisCART19ADrug
ThisCART19A is a new type CAR-T therapy for patients with r/r B-ALL.
Fludarabine Oral TabletDrug
Fludarabine is used for lymphodepletion.
CyclophosphamideDrug
Cyclophosphamide is used for lymphodepletion.
VP-16Drug
Also called etoposide
VP-16 is used for lymphodepletion.
HSCTProcedure or surgery
Hematological stem cell transplantation
| Study group | Role | What they receive |
|---|---|---|
| ThisCART19A cells infusion and HSCT | Experimental | In this study, allogeneic anti-CD19 CAR T cell (ThisCART19A) infusion is used to treat patients with refractory or relapsed CD19 positive B cell acute lymphoblastic leukemia.
After patients achieve MRD- remissions through ThisCART19A, they will subsequently receive hematological stem cell transplantations. Receives: Drug: ThisCART19A; Drug: Fludarabine Oral Tablet; Drug: Cyclophosphamide; Drug: VP-16; Procedure: HSCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limited toxicity(DLT) observation in patient with B-ALL in each dose level during dose escalation and dose expansion stage
DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level.
Measured: 28 days
Overall Complete Response (OCR) Rate (Complete Remission [CR]+ Complete Remission With Incomplete Hematologic Recovery [CRi]) within 3 months
OCR rate within 3 months: percentage of participants achieving CR+CRi within 3 months after CAR-T cell infusion.
Measured: 3 months
Secondary outcomes (5)
Minimum Residual Disease (MRD) Negative Remission Rate
MRD was assessed utilizing multicolor flow cytometry to detect residual cancerous cells with a sensitivity of 10^-4. MRD negative remission was defined as MRD < 10^-4 threshold. Percentage of participants with MRD negative remission was reported.
Measured: 3 months
Duration of response(DOR) during dose escalation stage and expansion stage
DOR was defined as the time from first CR or CRi to relapse or any death in the absence of documented relapse.
Measured: 24 months
RFS (Relapse-free Survival)
RFS is defined as the time from the date of ThisCART19A infusion to the date of disease relapse or death from any cause.
Measured: 24 months
EFS (Event-free Survival)
EFS is defined as the time from the date of ThisCART19A infusion to the date of disease relapse, progression, genetic relapse or death from any cause.
Measured: 24 months
OS (Overall Survival)
OS is defined as the time from the date of ThisCART19A infusion to the date of death from any cause.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2022
- Study start15 Oct 2022 (estimated)
- Primary completion22 Jan 2025 (estimated)
- Study completion22 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Allogeneic, CAR-T, Protein Sequestration, Non-gene EditedStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single Group Assignment
- Masking
- None (open label)
- Enrolment
- 19 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundamenta Therapeutics, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yongping Song, Ph.D, Principal investigator, The First Affiliated Hospital of Zhengzhou University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05576181
- Sponsor's protocol ID
- ThisCART19 FT400-007
- Status last verified
- Sep 2022
- First submitted
- 23 Sep 2022
- Last updated
- 12 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Dose-escalation Study to Evaluate the Safety and Efficacy of Allogeneic CAR-T Targeting CD19 Bridging Hematopoietic Stem Cell Transplantation in Patients With Refractory or Relapsed B Cell Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT05576181
- Acronym / sponsor ID
- ThisCART19 FT400-007
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 19 participants (estimated)
- Lead sponsor
- Fundamenta Therapeutics, Ltd.Industry (pharma, biotech, devices)
- Collaborators
- The First Affiliated Hospital of Zhengzhou University
- Study start
- 15 Oct 2022 (estimated)
- Primary completion
- 22 Jan 2025 (estimated)
- Study completion
- 22 Jul 2025 (estimated)
- First posted
- 12 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a a phase 1, open label study to assess the safety and efficacy of ThisCART19 (Allogeneic CAR-T targeting CD19) Bridging Hematopoietic Stem Cell Transplantation in patients with refractory or relapsed B cell acute lymphoblastic leukemia (r/r B-ALL).
Detailed description
This is a phase 1, single-center, nonrandomized, open-label, dose-escalation study to evaluate the safety and efficacy of ThisCART19A Bridging Hematopoietic Stem Cell Transplantation in patients with CD19 positive r/r B-ALL and identify a treatment regimen most likely to result in clinical efficacy while maintaining a favorable safety profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single Group Assignment
| Arm | Type | Receives |
|---|---|---|
| ThisCART19A cells infusion and HSCT | Experimental | Drug: ThisCART19A, Drug: Fludarabine Oral Tablet, Drug: Cyclophosphamide, Drug: VP-16, Procedure: HSCTIn this study, allogeneic anti-CD19 CAR T cell (ThisCART19A) infusion is used to treat patients with refractory or relapsed CD19 positive B cell acute lymphoblastic leukemia. After patients achieve MRD- remissions through ThisCART19A, they will subsequently receive hematological stem cell transplantations. |
Who may qualify
- Ages
- 14 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (25 listed)
- All subjects or legal representatives must sign a voluntary letter of consent approved by the IRB in person prior to the commencement of any screening procedure;
- Patients diagnosed with B-ALL;
- No gender limitation, Age 14 years to 75 years (both upper and lower limits included);
- Consistent with the diagnosis of recurrent refractory B-ALL. Recurrence： was defined as the recurrence of lymphoblasts（≥5%） in peripheral blood or bone marrow or extramedullary diseasefor patients who had acquired CR ; Refractory ：was defined as failure to CR or CRi at the end of induction therapy (generally referred to 4-week regimen or Hyper-CVAD regimen);Patients with Ph+ R/R ALL who failed after 2-line TKI treatment, were intolerant to TKI treatment or were not suitable for TKI treatment; The following factors can coexist:
- The expected survival time is ≥12 weeks;
Key exclusion criteria (16 listed)
- Allergic to preconditioning measures;
- Diagnosis of chronic myelogenous leukemia lymphoid blast crisis;
- Isolated extramedullary relapse;
- Presence of CNS-3 disease or CNS-2 disease with neurological changes;
- Imaging confirmed the presence of central nervous system involvement;
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 |
|---|---|---|
| ThisCART19AThisCART19A is a new type CAR-T therapy for patients with r/r B-ALL. | Drug | ThisCART19A cells infusion and HSCT |
| Fludarabine Oral TabletFludarabine is used for lymphodepletion. | Drug | ThisCART19A cells infusion and HSCT |
| CyclophosphamideCyclophosphamide is used for lymphodepletion. | Drug | ThisCART19A cells infusion and HSCT |
| VP-16Also: etoposideVP-16 is used for lymphodepletion. | Drug | ThisCART19A cells infusion and HSCT |
| HSCTHematological stem cell transplantation | Procedure or surgery | ThisCART19A cells infusion and HSCT |
Primary outcome
Dose limited toxicity(DLT) observation in patient with B-ALL in each dose level during dose escalation and dose expansion stage
Time frame: 28 days
DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level.
Overall Complete Response (OCR) Rate (Complete Remission [CR]+ Complete Remission With Incomplete Hematologic Recovery [CRi]) within 3 months
Time frame: 3 months
OCR rate within 3 months: percentage of participants achieving CR+CRi within 3 months after CAR-T cell infusion.
5 secondary outcomes
Minimum Residual Disease (MRD) Negative Remission Rate
Time frame: 3 months
Duration of response(DOR) during dose escalation stage and expansion stage
Time frame: 24 months
RFS (Relapse-free Survival)
Time frame: 24 months
EFS (Event-free Survival)
Time frame: 24 months
OS (Overall Survival)
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2022.
- Individual participant dataSharing planned: No
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.
Yongping Song, Ph.D principal investigator
The First Affiliated Hospital of Zhengzhou University
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ThisCART19A, Fludarabine Oral Tablet and Cyclophosphamide in people with Allogeneic, CAR-T, Protein Sequestration, Non-gene Edited, run by Fundamenta Therapeutics, Ltd..
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 25 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 12 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jun Li, Ph.D (+86-18662604088, jli@ctigen.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limited toxicity(DLT) observation in patient with B-ALL in each dose level during dose escalation and dose expansion stage (time frame: 28 days). The study lists 2 primary outcomes in all. 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 12 Oct 2022.