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B Cell LymphomaNCT03302403

Clinical Study of Redirected Autologous T Cells With a Chimeric Antigen Receptor in Patients With Malignant Tumors

A study testing CAR-CD19 T cell, CAR-BCMA T cell and CAR-GPC3 T cell in people with B Cell Lymphoma and B Cell Leukemia, run by Kang YU 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 The sponsor has not verified this record for over two years, so it may be out of date.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

A single arm, open-label pilot study is designed to determine the safety, efficacy and cytokinetics of CAR T cells in patients with malignant tumors with positive antigen targets. CAR T cells are genetically engineered to express single-chain variable fragment (scFv) targeting indication-specific antigens. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
B Cell Lymphoma, B Cell Leukemia, Myeloma
What is being tested?
CAR-CD19 T cell, CAR-BCMA T cell and CAR-GPC3 T cell
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteChina
Study dates
29 Dec 2017to 12 Dec 2023
Phase
Interventional
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 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • B-Cell Lymphoblastic Leukaemia/Lymphoma
  • Patients aged between 18 ~ 65 with B-cell lymphoblastic leukaemia/lymphoma.
  • CD19-positive B-cell lymphoblastic leukaemia/lymphoma.
  • Patients with unmet medical needs for which there are no effective therapies known at this time:
  • Relapsed or Refractory (r/r) Acute Lymphoblastic Leukemia (ALL)
  • Patients with r/r ALL for whom hematopoietic stem cell transplantation (HSCT) is not suitable due to following reasons:
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  • Age;
  • Excessive tumor burden or concomitant disease;
  • No donor available.
  • CD19-positive Follicular Lymphoma:
  • At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy;
  • Less than 6 months between last chemotherapy and disease progression (most recent progression free interval < 6 months);
  • Disease progression after most recent systemic therapy (chemotherapy, MoAb, etc.).
  • Chronic Lymphocytic Leukemia (CLL)
  • At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy);
  • Less than6 months between last chemotherapy and disease progression (most recent progression free interval < 6 months);
  • Not eligible or appropriate for conventional HSCT.
  • Disease progression after most recent systemic therapy (chemotherapy, MoAb, etc.).
  • Mantle Cell Lymphoma
  • At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy);
  • Disease progression after most recent systemic therapy (chemotherapy, MoAb, etc.)；
  • Relapsed after prior autologous SCT.
  • B-Cell Prolymphocytic Leukemia (PLL)
  • Relapsed or residual disease after at least 1 prior therapy and not eligible for HSCT.
  • CD19-positive Diffuse Large B Cell Lymphoma
  • At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy;
  • Stage III-IV disease.
  • Less than 6 months between last chemotherapy and disease progression (most recent progression free interval < 6 months);
  • Disease progression after most recent therapy (chemotherapy, MoAb, etc.).
  • Expected survival > 12 weeks.
  • At least one measurable lesion (≥ 10 mm) for patients with lymphoma.
  • ECOG scores 0-1, or KPS scores > 70.
  • Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis.
  • WBC ≥ 2.5×10^9/L; PLT ≥ 60×10^9/L (for patients with lymphoma); Hb ≥ 9.0 g/dL; LY ≥ 0.47×10^9/L; LY% ≥ 15%.
  • Serum Alb ≥ 30 g/L.
  • Serum creatinine ≤ 1.5 ULN.
  • ALT ≤ 2.5 ULN; AST ≤ 2.5 ULN.
  • Serum total bilirubin ≤ 1.5 ULN. The above lab results should not include those obtained from continuous supportive treatment that is ongoing.
  • Myeloma
  • Patients aged between 18 ~ 75 with relapsed or refractory multiple myeloma.
  • Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination.
  • Patients with relapsed or refractory malignancies who meet the following descriptions:
  • Curative efficacy is little or disease progressed after 2 courses of standard treatment regimen;
  • Disease relapsed after chemotherapy or HSCT. Curative efficacy is little or disease progressed after 2 courses of original treatment regimen;
  • More than 30 days between last treatment and disease progression;
  • There is no indication for HSCT at present;
  • Disease progression is defined as per "Chinese Guidelines for Diagnosis and Treatment of Multiple Myeloma (Version 2015)". One or more of the following conditions should be met:
  • Serum M-protein increases ≥ 25% (absolute increase should be ≥ 5 g/L). If serum M protein is ≥ 50 g/L at baseline, increase of serum M protein can be ≥ 10 g/L; ii. Urine M-protein increases ≥ 25% (absolute increase should be ≥ 200 mg/24 h); iii. If the serum and urine M-protein are not detectable, a ≥ 25% increase in the difference between involved and uninvolved FLC levels is required (absolute increase should be ≥ 100 mg/L); iv. Bone marrow plasma cell percentage increases ≥ 25% (absolute increase should be ≥ 10%); v. Size of existing bone lesions or soft tissue plasmacytomas increased by ≥ 25%, or development of new lytic bone lesions or oft tissue plasmacytomas; vi. Development of hypercalcemia that can be attributed to plasma cell proliferative disorder (corrected calcium is > 2.8 mmol/L or 11.5 mg/dL).
  • Expected survival > 12 weeks.
  • Disease is measurable, and at least one of the following conditions should be satisfied:
  • Serum M-protein is ≥ 10 g/L;
  • 24-hour urine M-protein is ≥ 200 mg;
  • Serum FLC is ≥ 5 mg/dL;
  • Plasmacytomas that can be measured or evaluated by imaging;
  • Bone marrow plasma cell percentage is ≥ 20%.
  • ECOG scores 0 - 1 or CCI scores ≤ 2.
  • Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis.
  • WBC ≥ 1.5×10^9/L; PLT ≥ 45×10^9/L; Hb ≥ 9.0 g/dL.
  • Serum creatinine ≤ 1.5 ULN.
  • ALT ≤ 2.5 ULN; AST ≤ 2.5 ULN. The above lab results should not include those obtained from continuous supportive treatment that is ongoing.
  • Hepatocellular Carcinoma (HCC)
  • Patients aged 18 ~ 70 with refractory hepatocellular carcinoma.
  • Patients with HCC that cannot be eradicated by resection who have received ablation or resection in the last 4 to 12 weeks.
  • IHC testing confirmed as GPC3-positive HCC.
  • Expected survival > 12 weeks.
  • At least one measurable lesion (≥ 10 mm).
  • Cirrhosis of the liver: Child-Pugh Class A, or Child-Pugh Class B scored at 7.
  • ECOG scores 0 - 1 or KPS scores > 70.
  • Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis.
  • Hematology:
  • WBC ≥ 2.5×10^9/L; PLT ≥ 60×10^9/L; Hb ≥ 9.0 g/dL; MID ≥ 1.0×10^9/L; LY ≥ 0.4×10^9/L.
  • Blood Chemistry:
  • Serum Alb ≥ 30 g/L; Serum lipase and serum amylase < 1.5 ULN; Serum creatinine ≤ 1.5 ULN; ALT ≤ 5 ULN; AST ≤ 5 ULN; Serum total bilirubin ≤ 2.5 ULN.
  • Coagulation Test:
  • Prothrombin time is at most 4 seconds longer than normal value.
  • Able to understand and sign the informed consent. All test results should be within their normal ranges, and patients are not receiving continuous supportive treatment.
  • Pancreatic Carcinoma and Adenocarcinoma of Esophagogastric Junction
  • Patients aged 18 ~ 70 with pathologically confirmed advanced pancreatic carcinoma and adenocarcinoma of esophagogastric junction.
  • IHC testing confirmed as Claudin18.2 positive.
  • Patients with advanced pancreatic carcinoma and adenocarcinoma of esophagogastric junction that cannot be eradicated by resection.
  • Expected survival after first dose of study drug > 12 weeks.
  • At least one measurable lesion (≥ 10 mm) available for imaging assessment.
  • ECOG scores 0 - 1.
  • Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis.
  • WBC ≥ 2.5×10^9/L; PLT ≥ 100×10^9/L; Hb ≥ 9.0 g/dL; MID ≥ 1.5×10^9/L; LY ≥ 0.47×10^9/L; LY% ≥ 15%.
  • Serum Alb ≥ 30 g/L.
  • Serum lipase and serum amylase < 1.5 ULN.
  • Serum creatinine ≤ 1.5 ULN.
  • ALT ≤ 2.5 ULN; AST ≤ 2.5 ULN; If osseous metastasis or liver metastasis is developed and alkaline phosphatase is > 2.5 ULN, than ALT and AST should be < 1.5 ULN.
  • Serum total bilirubin ≤ 1.5 ULN.
  • PT: INR < 1.7; PT < (ULN + 4) s All test results should be within their normal ranges, and patients are not receiving continuous supportive treatment.

Who cannot join

  • Patients with any of the following conditions are not eligible for this study.
  • Transduction of target lymphocytes < 10%, expansion in response to αCD3/CD28 costimulation < 5-fold.
  • Pregnant or lactating women.
  • HIV positive, or HCV positive
  • Uncontrolled active infection, including active tuberculosis and HBV DNA copies ≥ 1×10^3 copies/mL.
  • Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
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  • Allergic to immunotherapies and related drugs.
  • Patients with heart disease for which treatment is needed or with poorly controlled hypertension.
  • Hyponatremia: serum sodium level < 125 mmol/L.
  • Baseline serum potassium < 3.5 mmol/L (taking potassium supplements before participating in the study to raise potassium level is acceptable).
  • Previous treatment with chemoradiotherapy, immunotherapy and tumor-targeting drug conducted 2 weeks prior to participation in this study or blood collection.
  • Patients have undertaken immunosuppressor for graft-versus-host disease (GVHD) within 4 weeks before participation in this study or blood collection, or the patient is diagnosed with acute or chronic GVHD.
  • Other severe disease that may restrain patients from participating in this study (e.g. diabetes, severe cardiac dysfunction, myocardial infarction or unstable arrhythmias or unstable angina in recent 6 months, gastric ulcer, active autoimmune disease, etc.).

Trial locations and contacts

1 site in 1 country.

China1 site

  • First Affiliated Hospital of Wenzhou Medical University

    Wenzhou, Zhejiang, 325000

Other trials in China

About this study

A single arm, open-label pilot study is designed to determine the safety, efficacy and cytokinetics of CAR T cells in patients with malignant tumors with positive antigen targets.

CAR T cells are genetically engineered to express single-chain variable fragment (scFv) targeting indication-specific antigens.

The investigational CAR T cells and proposed indications are as follows:

CAR-CD19 T cells for B cell leukaemia/lymphoma; CAR-BCMA T cells for myeloma; CAR-GPC3 T cell for hepatocellular carcinoma; CAR-CLD18 T cells for pancreatic carcinoma and adenocarcinoma of esophagogastric junction.

Read the detailed description

This study is designed to determine the safety, tolerability and engraftment potential of lentivirus-transduced CAR T cells in patients with malignant tumors.

Primary objectives:

  1. Determine the safety and tolerability of CAR T cells (autologous T cells transduced with chimeric antigen receptors recognizing CD19, BCMA, GPC3 and Claudin18.2) in patients with malignant tumors (B-cell lymphoblastic leukaemia/lymphoma, myeloma, hepatocellular carcinoma, pancreatic carcinoma and adenocarcinoma of esophagogastric junction).
  2. Observe the cytokinetics of CAR T cells.

Secondary objectives:

  1. Observe the efficacy of CAR T cells in patients with malignant tumors.
  2. Make an evaluation on the distribution and in vivo survival of CAR T cells in targeted tissues.
  3. Observe the immunogenicity of CAR T cells, and determine if there are anti-scFv cellular immune response and anti-scFv humoral immune response.
  4. Observe the changes of cell subsets for CAR T cells against T cells (Tcm, central memory T lymphocytes; Tem, effector memory T lymphocytes; Treg, regulatory T-lymphocytes).
Being tested
CAR-CD19 T cell, CAR-BCMA T cell, CAR-GPC3 T cell, CAR-CLD18 T cell, Fludarabine
Medical subject headings
Lymphoma, B-Cell, Leukemia, B-Cell, Neoplasms, Plasma Cell, Carcinoma, Hepatocellular, Pancreatic Neoplasms

What participants receive

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

  • CAR-CD19 T cellGenetic

    Also called CD19-redirected Autologous Cell

    Self-controlled dose escalation and classic "3+3" dose escalation will be applied.

  • CAR-BCMA T cellGenetic

    Also called BCMA-redirected Autologous Cell

    Self-controlled dose escalation and classic "3+3" dose escalation will be applied.

  • CAR-GPC3 T cellGenetic

    Also called GPC3-redirected Autologous Cell

    Self-controlled dose escalation and classic "3+3" dose escalation will be applied.

  • CAR-CLD18 T cellGenetic

    Also called Claudin18.2-redirected Autologous Cell

    Self-controlled dose escalation and classic "3+3" dose escalation will be applied.

  • FludarabineDrug

    Fludarabine is used for lymphodepletion.

  • CyclophosphamideDrug

    Cyclophosphamide is used for lymphodepletion.

Study groups in NCT03302403
Study groupRoleWhat they receive
CAR T cellExperimentalIn this study, autologous T cells transduced with a chimeric antigen receptor are used to treat patients with malignant tumors: CAR-CD19 T cell is for the treatment of B-cell Leukaemia/Lymphoma; CAR-BCMA T cell is for the treatment of Myeloma; CAR-GPC3 T cell is for the treatment of Hepatocellular Carcinoma; CAR-CLD18 T cell is for the treatment of Pancreatic Carcinoma and Adenocarcinoma of Esophagogastric Junction. Route of administration: Intravenous injection. Lymphodepletion conditioning: Lymphodepletion will be conducted several days prior to CAR T cell infusion, which may improve in vivo cell count and survival of T cells. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
Receives: Genetic: CAR-CD19 T cell; Genetic: CAR-BCMA T cell; Genetic: CAR-GPC3 T cell; Genetic: CAR-CLD18 T cell; Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

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

  1. Number of participants with CRA T-related adverse events as assessed by CTCAE v4.03

    Number of participants with study related adverse events which are defined as laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the infusion until week 24, including infusion related toxicity and any toxicity possibly related to CAR T cells.

    Measured: 24 weeks

Secondary outcomes (1)

  1. Engraftment

    Duration of in vivo survival of CAR T cells is defined as "engraftment". The primary engraftment endpoint is the number of DNA vector copies per mL blood of CAR T cells at regular intervals through 24 hours following the initial infusion. PCR for CAR T vector sequences will be performed until any 2 sequential tests are negative, documented as engraftment of CAR T cells.

    Measured: 2 years

Timeline

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

  1. First posted5 Oct 2017
  2. Study start29 Dec 2017
  3. Primary completion12 Dec 2020 (estimated)
  4. Study completion12 Dec 2023 (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
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03302403
Sponsor's protocol ID
CGZ001
Status last verified
Oct 2020
First submitted
26 Sep 2017
Last updated
8 Oct 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Dong R, Jiang S, Chen Y, Ma Y, Sun L, Xing C, Zhang S, Yu K. Prognostic Significance of Cytokine Release Syndrome in B Cell Hematological Malignancies Patients After Chimeric Antigen Receptor T Cell Therapy. J Interferon Cytokine Res. 2021 Dec;41(12):469-476. doi: 10.1089/jir.2021.0057.

    PubMed 34935483

Questions about this trial

What is this clinical trial studying?

A study testing CAR-CD19 T cell, CAR-BCMA T cell and CAR-GPC3 T cell in people with B Cell Lymphoma and B Cell Leukemia, run by Kang YU 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 91 inclusion and 13 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 8 Oct 2020. 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.

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?

Number of participants with CRA T-related adverse events as assessed by CTCAE v4.03 (time frame: 24 weeks). 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 NCT03302403, which also lists 1 linked publication.

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 8 Oct 2020.

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