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ALL, Childhood B-CellEarly Phase 1NCT04173988

Study of alloCART-19 Cell Therapy in Pediatric Patients With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia

A Early Phase 1 study testing alloCART-19, Cyclophosphamide and Fludarabine in people with ALL, Childhood B-Cell, run by Children's Hospital of Fudan University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this study is to evaluate the safety and tolerability of CD19-Directed Allogeneic Chimeric Antigen Receptor T- cell (alloCART-19)therapy in pediatric patients with relapsed/refractory acute lymphoblastic leukemia（ALL）. Read more about this study

Who is it for?
Ages 1 year to 18 years
Conditions the study is for
ALL, Childhood B-Cell
What is being tested?
alloCART-19, Cyclophosphamide and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteChina
Study dates
9 Jan 2020to 20 Jul 2025
Phase
Early 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 1 year to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Signed informed consent and assent forms if applicable must be obtained prior to the start of any research procedure
  • Age 1 year at the time of screening to age 18 years at the time of initial diagnosis
  • Relapsed/refractory pediatric ALL that meet one of the following conditions:
  • Incomplete patients with conventional chemotherapy regimens, or primary refractory patients who failed to complete remission with 2 courses of standard chemotherapy regimen, or did not achieve complete remission after first-line or multi-line salvage chemotherapy
  • Early recurrence after complete remission (< 12 months) or late recurrence after complete remission (≥ 12 months) and chemotherapy was not completely relieved by the standardized two course induction regimens
  • Recurrence after autologous or allogeneic hematopoietic stem cell transplantation
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  • Patients who are Philadelphia chromosome-positive (Ph+) are eligible if they have failed at least 2 lines of chemotherapy and have failed two lines of TKI therapy or if TKI therapy is contraindicated.
  • For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of study entry
  • Karnofsky performance status of > 60 at screening
  • During the screening period and within 10 days of treatment, adequate organ function defined as:
  • Renal Function: serum creatinine ≤ 2 x ULN
  • Liver Function: ALT and/or AST ≤ 10 x ULN (depending on age), bilirubin ≤ 5 x ULN
  • Pulmonary Function: oxygen saturation ≥ 91%
  • Heart Function: echocardiogram (ECHO): left ventricular ejection fraction (LVEF) ≥ 45%
  • Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening or immunological/molecular biological results with persistent MRD
  • Female subjects of childbearing age must have a negative serum or urine pregnancy test during the screening period and agree to take effective contraceptive measures during the trial period until the last follow-up

Who cannot join

  • Pregnant or lactating women
  • Unable to tolerate venipuncture
  • Prior history of:
  • Allogeneic cell therapy (including hematopoietic stem cell transplantation) within 6 weeks of alloCART-19 infusion
  • Any live vaccine within 4 weeks of alloCART-19 infusion and/or plan to receive live vaccine after enrollment
  • Immunosuppressants for GvHD treatment within 4 weeks of alloCART-19 infusion
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  • Systemic corticosteroid treatment at doses greater than 5 mg/day prednisone*3 days (or equivalent corticosteroids) within 72 hours prior to alloCART-19 treatment
  • Before receiving alloCART-19 treatment, had received the following anti-neoplastic therapies: Tyrosine kinase inhibitors and hydroxyurea within 72 hours; Vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate < 25 mg/m2, cytosine arabinoside < 100 mg/m2/day, or asparaginase (non-pegylated) within 1-week; Pegylated-asparaginase within 4 weeks; Central nervous system disease prophylaxis (e.g. intrathecal methotrexate) within 1 week; Investigational drug treatment within 4 weeks
  • Had received the following anti-neoplastic radiotherapy before receiving alloCART-19 treatment: Radiotherapy for non-CNS sites within 2 weeks; Radiotherapy for the CNS site within 8 weeks
  • Have the following medical history:
  • Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD)
  • Isolated extramedullary disease recurrence (e.g. central nervous system and testis)
  • Previous or active central nervous system (CNS) diseases such as seizures, cerebral ischemia/bleeding, dementia, cerebellar disease or any autoimmune disease involving CNS
  • Previous malignant tumors (excluding curative trends and inactive skin cancer in situ or cervical cancer)
  • Genetic syndromes associated with bone marrow failure states: such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome (excluding Down syndrome)
  • Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening period)
  • History of HIV, or HIV-positive test within 8 weeks of screening period
  • Any uncontrolled serious infection during the screening period
  • Severe, poorly controlled concomitant diseases such as, but not limited to, nervous system, kidney, liver, endocrine or gastrointestinal disorders that may be deemed by the investigator to interfere with the inclusion of the subject in the study.
  • Any clinical abnormalities including but not limited to the nervous system, cardiovascular system, blood and lymphatic system, immune system, kidney, liver, gastrointestinal tract, respiratory system, metabolism and bones that may be deemed by the investigator to interfere with the inclusion of a subject in the study.
  • The following treatments and/or medications must be excluded:
  • Simultaneous application of other anti-neoplastic drugs, including traditional Chinese herbal medicines
  • Drugs that prolong the QT interval (including Ia and III antiarrhythmic drugs)
  • Daily oxygen therapy
  • long-term use of corticosteroids (except for inhaled and topical use)
  • Any circumstance or condition that in the judgement of the investigator may interfere with the subject's participation in the trial.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Children's Hospital of Fudan University

    Shanghai, Minhang, 201102

Other trials in China

About this study

Official title: A Single Center, Open Label, Single Arm Exploratory Clinical Study of CD19-Directed Allogeneic Chimeric Antigen Receptor CART-cell Immunotherapy Cell Therapy in Pediatric Patients With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia

The purpose of this study is to evaluate the safety and tolerability of CD19-Directed Allogeneic Chimeric Antigen Receptor T- cell (alloCART-19)therapy in pediatric patients with relapsed/refractory acute lymphoblastic leukemia（ALL）.

Read the detailed description

This is a single center, open label, single arm, dose escalation study to explore the safety, tolerability, and pharmacokinetic / pharmacodynamic profile of CD19-Directed Allogeneic Chimeric Antigen Receptor T- cell (alloCART-19) in pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia. The study will also assess the preliminary efficacy of CD19-Directed Allogeneic Chimeric Antigen Receptor T- cell (alloCART-19). For this exploratory clinical trial, approximately 3-6 patients will be enrolled. During dose escalation, at least one evaluable patient will be enrolled at each dose level. Once DLT is reached, 1 to 3 additional patients will be enrolled at the dose level below DLT, which has been tested and determined to be safe in the trial, to evaluate the optimal safe and therapeutic dose to be approved by the investigator and sponsor.

Being tested
alloCART-19, Cyclophosphamide, Fludarabine
Keywords
Allogeneic CAR-T19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • alloCART-19Genetic

    Also called allogeneic CAR-T19

    AlloCART-19 is an allogeneic CAR-T cell product targeting CD19.

    • For children with body weight ≤ 50 kg, dose range for dose escalation will be 0.5 - 5 × 10^6 CAR+ cells/kg
    • For children with body weight > 50 kg, dose range for dose escalation will be 0.25 - 2.5 × 10^8 CAR+ cells.

  • CyclophosphamideDrug

    Also called no other intervention names

    Chemotherapy for lymphodepletion

  • FludarabineDrug

    Also called no other intervention names

    Chemotherapy for lymphodepletion

Study groups in NCT04173988
Study groupRoleWhat they receive
alloCART-19ExperimentalFor the very first patient, the initial dose could be administered via one or three intravenous infusions within 1 to 5 days. Starting from the second patient, the investigator will decide whether to use single or multiple alloCART-19 infusions, based on the treatment experience at previous dose level(s) and the patient's baseline disease burdens. A lymphodepletion conditioning with cyclophosphamide and fludarabine will be conducted before alloCART-19 infusion.
Receives: Genetic: alloCART-19; Drug: Cyclophosphamide; Drug: Fludarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicity

    Dose Limiting Toxicity (DLT) is defined as patients with the adverse event (AE) or laboratory abnormality per Lee DW and Locke FL standards and management guideline, and should be possibly related to alloCART-19 cell therapy, and should be unrelated to the disease itself, disease progression, concomitant diseases or concomitant medication. DLT will be analyzed as categorical variable，coded as 1 for DLT occur, 0 for no DLT.

    Measured: Day 28 after the first alloCART-19 infusion

Secondary outcomes (3)

  1. The occurrence of adverse events

    The adverse events (AE) is a composite variable including liver and kidney function damage, nausea, vomiting, arrhythmia and dyspnea. The variable would be coded as 1 if any of these events occurs after the first alloCART-19 infusion while 0 for none . These adverse events would be measured by assessment scale method according to NCI CTC AE v5.0 classification standard.

    Measured: After the first alloCART-19 infusion for 2 year

  2. Objective Response Rate

    Objective Response Rate（ORR）is defined as the proportion of patients whose tumor volume shrank to a predetermined value and the minimum time limit required.

    ORR = complete remission (CR) + incomplete complete remission (CRi)

    Measured: Day 28 and 3 months after the first alloCART-19 infusion

  3. Best Overall Response

    Best Overall Response（BOR）at 28 days and 3 months after drug infusion was evaluated to preliminarily evaluate the optimal efficacy of alloCART-19 infusion in patients.

    Measured: Day 28 and 3 months after the first alloCART-19 infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Nov 2019
  2. Study start9 Jan 2020
  3. Primary completion20 Oct 2024 (estimated)
  4. Study completion20 Jul 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04173988
Sponsor's protocol ID
2019-272
Status last verified
Mar 2024
First submitted
13 Nov 2019
Last updated
15 Mar 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing alloCART-19, Cyclophosphamide and Fludarabine in people with ALL, Childhood B-Cell, run by Children's Hospital of Fudan University at 1 site in China.

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 16 inclusion and 26 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 15 Mar 2024. 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 China. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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?

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?

Dose Limiting Toxicity (time frame: Day 28 after the first alloCART-19 infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04173988.

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 15 Mar 2024.

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