Acute Lymphoblastic Leukemia, in RelapsePhase 1CARTHIAE-1NCT05705570
Clinical Trial Using CAR- T Cells for Treatment of Patients With Refractory or Relapsed CD19-positive B Lymphoid Malignancies
A Phase 1 study testing Cyclophosphamide, Fludarabine and Chimeric antigen receptor T cells to be implemented in a "3 + 3" design on day 0 in people with Acute Lymphoblastic Leukemia, in Relapse and Acute Lymphoblastic Leukemia Refractory, run by Nelson Hamerschlak at 1 site in Brazil.
Trial summary
This is a phase l, single arm, prospective open, dose-escalation study in patients with relapsed or refractory CD19-positive B cell malignancies (ALL, NHL, CLL). The trial will include adult and pediatric patients. Read more about this study
- Who is it for?
- Ages 2 to 70 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, in Relapse, Acute Lymphoblastic Leukemia Refractory, B-cell Lymphoma Recurrent
- What is being tested?
- Cyclophosphamide, Fludarabine and Chimeric antigen receptor T cells to be implemented in a "3 + 3" design on day 0
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteBrazil
- Study dates
- 7 Feb 2023to 1 Dec 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 2 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subjects must have relapsed or refractory ALL, lymphoma or CLL treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve partial or complete remission with the last regimen.
- Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) subjects are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs).
- Subjects with DLBCL must have progressed, had SD, or recurred after initial treatment regimens that include an anthracycline and an anti-CD20 monoclonal antibody.
- Subjects with transformed FL, MZL, or CLL/SLL must have progressed, had SD or recurred with transformed disease after initial treatment for DLBCL.
- Subjects who relapse ≥12 months after therapy should have progressed after autologous transplant or been ineligible for autologous transplant.
- 2. The patient's disease must be CD19 positive, either by immunohistochemistry or flow cytometry analysis on the last biopsy available.
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- Age 2 to 70 years.
- Performance status: Adult Subjects: ECOG ≤ 2 for patients ≥ 16 years; Subjects < 16 years of age: lansky ≥ 50%
- Normal Organ and Marrow Functioning (supportive treatment is allowed according to institutional standards, i.e. filgrastim, transfusion)
- Total Bilirubin ≤ 2; AST (SGOT) ≤ 5 times the upper limit of normal; ALT (SGTP) ≤ 5 times the upper limit of normal; Serum creatinine ≤ 1.5; Pulse oximetry >91% on room air; No dyspnea or mild dyspnea (≤ Grade 1); Forced expiratory volume in 1 s (FEV1) ≥50% or carbon monoxide diffusion test (DLCO) ≥50% of predicted level; Left ventricular ejection fraction ≥ 45% confirmed by echocardiogram; Subjects must have the following hematologic function parameters: Neutrophils > 1000/uL; Absolute Lymphocyte Count > 100/uL; Platelets ≥ 50,000/L Patient should not be excluded if change of the above parameters due to spinal cord disease infiltration;
- Prior therapy wash-out - At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives, Blinatumomab with 4 months prior CAR-T infusion.
- For women of reproductive potential: use a highly effective contraceptive for at least 1 month prior to screening and agree to use a method during study participation and for an additional 4 months after CAR T-cell administration has ended.
- Subjects must have the ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Autologous transplant within 6 weeks of planned CAR-T cell infusion;
- History of allogeneic stem cell transplant 4 months prior CAR T cell infusion.
- Use of immunosuppression therapy;
- Patients must have completed immunosuppression therapy; Systemic corticosteroid therapy must be stopped more than 72 hours after infusion; Systemic drugs for graft-versus-host disease should be withheld at least 4 weeks prior to infusion;
- Presence of graft-versus-host disease Grade ≥ 2;
- Receiving CAR T cell treatment outside of this protocol;
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- Active central nervous system or meningeal involvement by tumor. Subjects with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced MRI imaging for at least 90 days prior to registration.
- History of active malignancy other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast).
- HIV infection; HTLV
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects.
- Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy
- Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
- Serious and/or potentially fatal medical conditions
- Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.
- History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months.
- Hypersensitivity against any drug or its ingredients/impurities that is scheduled or likely to be given during trial participation, e.g. as part of the mandatory lymphodepletion protocol, pre-medication for infusion, rescue medication/salvage therapies for treatment related toxicities;
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Hospital Israelita Albert Einstein
São Paulo, São Paulo, 05652-900
Fernanda F Assir, RN, +5511997748793, fernanda.assir@einstein.br
Mariana C. B. Velloso, RN, +5511986049066, mariana.velloso@einstein.br
About this study
Official title: A Phase I Clinical Trial Using Genetically Engineered Autologous T Cells to Express Chimeric Antigen Receptor (CAR) for Treatment of Patients With Refractory or Relapsed CD19-positive B Lymphoid Malignancies
This is a phase l, single arm, prospective open, dose-escalation study in patients with relapsed or refractory CD19-positive B cell malignancies (ALL, NHL, CLL). The trial will include adult and pediatric patients. There will be three individual cohorts, defined by disease biology: pediatric ALL and aggressive pediatric NHL (Cohort 1), adult ALL (Cohort 2) and adult NHL/CLL (Cohort 3).
Read the detailed description
The investigators will evaluate the safety of the MB-CART19.1 and determine the recommended dose levels for the Phase II clinical trial.
Dose evaluation will start in Cohorts 1 and 2 with Dose Level 1 (5x10e5 CAR T cells/Kg) and in Cohort 3 with Dose Level 2 1x10e6 CAR T cells/Kg) , sparing Dose Level 1 . Each of the cohorts will evaluate the safety of the CAR-T cells.
In each dose level of each of the three cohorts three 3 + 3 patients will be treated. A particular dose level will be expanded to 6 patients if one patient out of 3 patients treated at that particular dose level develops DLT. Once this occurs, further dose-escalations are halted until the dose has proven to be safe in the expanded cohort. If 2 or more in a cohort of 6 patients develop DLT no further dose escalation is allowed, and the next lower dose level will be expanded to 6 patients in total. The highest dose among the dose levels tested at which no more than one out of six patients experiences DLT will be considered the MTD. In Dose Level 3, three additional patients will be treated, if no DLT occurred. Dose Level 0 will be tested only if Dose Level 1 is not tolerable.
- Conditions
- Acute Lymphoblastic Leukemia, in Relapse, Acute Lymphoblastic Leukemia Refractory, B-cell Lymphoma Recurrent, B-cell Lymphoma Refractory, Chronic Lymphocytic Leukemia Recurrent, Chronic Lymphocytic Leukemia Refractory
- Being tested
- Cyclophosphamide, Fludarabine, Chimeric antigen receptor T cells to be implemented in a "3 + 3" design on day 0
- Keywords
- CAR T cell, CD19+ B-cell Malignancies
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Cyclophosphamide 60mg/Kg on day -6
FludarabineDrug
Fludarabine 25mg/m^2 IV on days -5 to -3
Chimeric antigen receptor T cells to be implemented in a "3 + 3" design on day 0Biological
Level -1 (1 x 105 cells/kg)
Level 1 [Starting dose] (5 x 105 cells/kg)
Level 2 (1 x 106 cells/kg)
Level 3 (2 x 106 cells/kg)
| Study group | Role | What they receive |
|---|---|---|
| Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells | Experimental | Lymphodepleting regimen, consisting of Cyclophosphamide 60mg/kg IV on day -6 and Fludarabine 25mg/m2 IV on days -5 to -3. Followed by infusion of Chimeric antigen receptor T-cells (CAR-T) on day 0 Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Chimeric antigen receptor T cells to be implemented in a "3 + 3" design on day 0 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of the recommended dose of CAR-T cells for a future phase II study
The RP2D will be the maximum tolerated dose (MTD) or the highest dose studied if an MTD is not obtained.
Measured: Until day 28 after CAR-T cells infusion
Secondary outcomes (4)
Response to treatment for each timepoint.
ORR in ALL (Rate of CR/CRh)
Measured: day 28
Response to treatment for each timepoint
ORR in NHL/CLL (Rate of CR/CRh)
Measured: day 28, patients not in CR on day 28: month 3
Assess overall survival (OS), progression-free survival (PFS).
Overall survival (OS) and progression-free survival (PFS) will be assessed by dose cohort and in the first two groups at the MTD (or at the highest dose studied).
Measured: at 1 year after CAR-T infusion
Phenotype and persistence of CAR-T
Blood samples for determination of persistence/phenotyping of infused CAR-T cells will be analysed.
Measured: days 2, 7, 10, 14, 28, weeks 8, 12, months 6, 12, 24, 36, 48, 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2023
- Study start7 Feb 2023
- Primary completion1 May 2028 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic Leukemia, in RelapseStudies 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
- A phase I study, with a "3+3" dose escalation design
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nelson Hamerschlak
- Sponsor type
- University, hospital or other
- Collaborators
- Miltenyi Biotec, Inc.
- Responsible party
- Sponsor-investigator, Nelson Hamerschlak, Hospital Israelita Albert Einstein
- Investigators
- Nelson Hamerschlak, MD, PhH, Principal investigator, Hospital Israelita Albert Einstein
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05705570
- Sponsor's protocol ID
- 30173220.5.0000.0071
- Acronym
- CARTHIAE-1
- Status last verified
- Sep 2025
- First submitted
- 20 Jan 2023
- Last updated
- 25 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- 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 25 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Trial Using Genetically Engineered Autologous T Cells to Express Chimeric Antigen Receptor (CAR) for Treatment of Patients With Refractory or Relapsed CD19-positive B Lymphoid Malignancies
- ClinicalTrials.gov ID
- NCT05705570
- Acronym / sponsor ID
- CARTHIAE-1 / 30173220.5.0000.0071
- Conditions
- Acute Lymphoblastic Leukemia, in Relapse, Acute Lymphoblastic Leukemia Refractory, B-cell Lymphoma Recurrent, B-cell Lymphoma Refractory, Chronic Lymphocytic Leukemia Recurrent, Chronic Lymphocytic Leukemia Refractory
- Keywords
- CAR T cell, CD19+ B-cell Malignancies
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Nelson HamerschlakUniversity, hospital or other
- Collaborators
- Miltenyi Biotec, Inc.
- Study start
- 7 Feb 2023 (actual)
- Primary completion
- 1 May 2028 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 31 Jan 2023 (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 phase l, single arm, prospective open, dose-escalation study in patients with relapsed or refractory CD19-positive B cell malignancies (ALL, NHL, CLL). The trial will include adult and pediatric patients. There will be three individual cohorts, defined by disease biology: pediatric ALL and aggressive pediatric NHL (Cohort 1), adult ALL (Cohort 2) and adult NHL/CLL (Cohort 3).
Detailed description
The investigators will evaluate the safety of the MB-CART19.1 and determine the recommended dose levels for the Phase II clinical trial.
Dose evaluation will start in Cohorts 1 and 2 with Dose Level 1 (5x10e5 CAR T cells/Kg) and in Cohort 3 with Dose Level 2 1x10e6 CAR T cells/Kg) , sparing Dose Level 1 . Each of the cohorts will evaluate the safety of the CAR-T cells.
In each dose level of each of the three cohorts three 3 + 3 patients will be treated. A particular dose level will be expanded to 6 patients if one patient out of 3 patients treated at that particular dose level develops DLT. Once this occurs, further dose-escalations are halted until the dose has proven to be safe in the expanded cohort. If 2 or more in a cohort of 6 patients develop DLT no further dose escalation is allowed, and the next lower dose level will be expanded to 6 patients in total. The highest dose among the dose levels tested at which no more than one out of six patients experiences DLT will be considered the MTD. In Dose Level 3, three additional patients will be treated, if no DLT occurred. Dose Level 0 will be tested only if Dose Level 1 is not tolerable.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A phase I study, with a "3+3" dose escalation design
| Arm | Type | Receives |
|---|---|---|
| Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Biological: Chimeric antigen receptor T cells to be implemented in a "3 + 3" design on day 0Lymphodepleting regimen, consisting of Cyclophosphamide 60mg/kg IV on day -6 and Fludarabine 25mg/m2 IV on days -5 to -3. Followed by infusion of Chimeric antigen receptor T-cells (CAR-T) on day 0 |
Who may qualify
- Ages
- 2 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Subjects must have relapsed or refractory ALL, lymphoma or CLL treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve partial or complete remission with the last regimen.
- Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) subjects are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs).
- Subjects with DLBCL must have progressed, had SD, or recurred after initial treatment regimens that include an anthracycline and an anti-CD20 monoclonal antibody.
- Subjects with transformed FL, MZL, or CLL/SLL must have progressed, had SD or recurred with transformed disease after initial treatment for DLBCL.
- Subjects who relapse ≥12 months after therapy should have progressed after autologous transplant or been ineligible for autologous transplant.
Key exclusion criteria (17 listed)
- Autologous transplant within 6 weeks of planned CAR-T cell infusion;
- History of allogeneic stem cell transplant 4 months prior CAR T cell infusion.
- Use of immunosuppression therapy;
- Presence of graft-versus-host disease Grade ≥ 2;
- Receiving CAR T cell treatment outside of this protocol;
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 |
|---|---|---|
| CyclophosphamideCyclophosphamide 60mg/Kg on day -6 | Drug | Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells |
| FludarabineFludarabine 25mg/m^2 IV on days -5 to -3 | Drug | Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells |
| Chimeric antigen receptor T cells to be implemented in a "3 + 3" design on day 0Level -1 (1 x 105 cells/kg) Level 1 [Starting dose] (5 x 105 cells/kg) Level 2 (1 x 106 cells/kg) Level 3 (2 x 106 cells/kg) | Biological | Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells |
Primary outcome
Determination of the recommended dose of CAR-T cells for a future phase II study
Time frame: Until day 28 after CAR-T cells infusion
The RP2D will be the maximum tolerated dose (MTD) or the highest dose studied if an MTD is not obtained.
4 secondary outcomes
Response to treatment for each timepoint.
Time frame: day 28
Response to treatment for each timepoint
Time frame: day 28, patients not in CR on day 28: month 3
Assess overall survival (OS), progression-free survival (PFS).
Time frame: at 1 year after CAR-T infusion
Phenotype and persistence of CAR-T
Time frame: days 2, 7, 10, 14, 28, weeks 8, 12, months 6, 12, 24, 36, 48, 60
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2025.
- 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.
Nelson Hamerschlak, MD, PhH principal investigator
Hospital Israelita Albert Einstein
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cyclophosphamide, Fludarabine and Chimeric antigen receptor T cells to be implemented in a "3 + 3" design on day 0 in people with Acute Lymphoblastic Leukemia, in Relapse and Acute Lymphoblastic Leukemia Refractory, run by Nelson Hamerschlak at 1 site in Brazil.
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 13 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 25 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. 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 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nelson Hamerschlak, MD, PhH (+551121517248, hamer@einstein.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of the recommended dose of CAR-T cells for a future phase II study (time frame: Until day 28 after CAR-T cells infusion). 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 25 Sep 2025.