Precursor B-Lymphoblastic Lymphoma/Leukaemia RefractoryPhase 2NCT03321123
MB-CART19.1 in Patients With R/R ALL
A Phase 2 study testing MB-CART19.1 in people with Precursor B-Lymphoblastic Lymphoma/Leukaemia Refractory, run by Shanghai Children's Medical Center.
Trial summary
Precursor-B acute lymphoblastic leukemia (ALL) is the most common cancer in childhood. Despite major advances in ALL therapy, 20% of children and 40-50% of adults fail state-of-the art first-line treatment. Read more about this study
- Who is it for?
- Ages 2 months to 18 years
- Conditions the study is for
- Precursor B-Lymphoblastic Lymphoma/Leukaemia Refractory
- What is being tested?
- MB-CART19.1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2017to 31 Dec 2019
- Phase
- Phase 2
- 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 2 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age ≤18 years (if deemed fit by treating investigator)
- CD19 expression must be detected on the malignant cells by flow cytometry.
- Patients with relapsed disease with >5% blasts in BM (M2 or M3) after at least one standard chemotherapy and one salvage regimen who are ineligible for allogeneic stem cell transplant (alloSCT)
- Patients have refractory disease activity precluding alloSCT at this time, or patients who have relapsed post alloSCT at least 100 days post-transplant, with no evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
- Patients with combined extramedullary ALL are eligible if extramedullary disease has been successfully cleared by conventional therapy at the time of inclusion (e.g. intrathecal chemotherapy, orchiectomy). This includes patients with combined CNS-2 (<5 WBC/µl CSF, with blasts on cytospin) or CNS-3 (5WBC/µl CSF, with blasts on cytospin) disease and patients with combined testicular relapse.
- Patients and/or parents must give their written informed consent/assent.
Who cannot join
- Rapidly progressive disease that in the estimation of live less than 12 weeks
- Isolated extramedullary relapse (CNS and/or testicular) in ALL
- Current autoimmune disease, or history of autoimmune disease with potential CNS involvement
- Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis)
- History of an additional malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease free for ≥3 years.
- Pulmonary function: Patients with pre-existing severe lung disease (FEV1 or FVC < 65%) or an oxygen requirement of >28% O2 supplementation or active pulmonary infiltrates on chest X-ray at the time scheduled for T cell infusion
- Cardiac function: Fractional shortening <28% or left ventricular ejection fraction <50% by echocardiography
- Renal function: Creatinine clearance <50 mL/min/1.73 m2
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Adoptive Therapy With MB-CART19.1 in Patients With Relapsed/Refractory CD19-positive B Cell Acute Lymphoblastic Leukemia
Precursor-B acute lymphoblastic leukemia (ALL) is the most common cancer in childhood. Despite major advances in ALL therapy, 20% of children and 40-50% of adults fail state-of-the art first-line treatment. But there is a strong need for alternative treatments to cure chemotherapy-refractory and relapsed B cell malignancies in pediatric patients. Relapsed and refractory B cell malignancies remain a therapeutic challenge, as these diseases are characterized by adverse survival. These cancers share a cell origin from the B-cell lineage and consequent surface expression of B-lineage markers such as CD19 and CD22. Chimeric antigen receptor (CAR) engineered T cell therapy has recently emerged as a new modality to target B cell malignancies. CARs couple a single-chain Fv (scFv) domain directed against a B-lineage-specific antigen to T-cell activating intracellular signaling domains. CAR gene-modified T cell interaction with target cells occurs in a HLA-independent fashion, so that a single vector can be used to treat all patients with cancers that express the target antigen. Miltenyi Biotec has established a semi-automated manufacturing process that can be made available to academic settings for systematic exploration of CAR strategies in advanced clinical studies. Closed-system operation, improved robustness, simplified work flows, and reduced labor intensity, while maintaining strict adherence to regulatory guidelines, allows for decentralized manufacturing. In the proposed phase II study, the investigator will explore autologous 2nd generation CD19 CAR T cell products in patients with relapsed and refractory disease incurable with standard therapies.
Read the detailed description
This is an open-label, non-randomized phase II paediatric study. In this study, eligible patients will receive autologous T cells transduced with the lentiviral vector pLTG1563 (MB-CART19.1) at a doesage of 2x10e6 ~2x10e7 CAR-transduced T cells/kg.
Upon enrollment, leukapheresis will be performed for MB-CART19.1 generation. Patients with high disease burden at screening (e.g. ALL with M3 marrow and 10.000/L blasts in peripheral blood) may receive bridging chemotherapy after leukapheresis, to avoid critical tumor lysis syndrome and cytokine release syndrome (CRS) by subsequent lymphodepleting chemotherapy and CAR transfer.
All patients will receive lymphodepleting chemotherapy with fludarabine 30 mg/m2/d intravenously (iv) on days -5,-4,-3 and -2 cyclophosphamide 500 mg/m2/d iv on day -3,-2 before CAR T cell transfer to enhance the in vivo expansion of CAR T cells.
Patients will receive freshly prepared MB-CART19.1 on day 0, corresponding to day 12 (48 hours) of manufacturing, at a dose of 2x10e6 ~2x10e7/kg MB-CART19.1 T cells as defined in the study design section. The appropriate volume for the target cell dose will be drawn up and given as an IV injection over 30 minutes through a large vein peripherally or centrally.
The primary objectives are:
- To assess the safety and tolerability of MB-CART19.1.
- To evaluate the biological activity of adoptive transfer of autologous MB-CART19.1 in patients with R/R CD19-positive B cell lymphoblastic leukemia.
The primary endpoint is Overall response rate (ORR):ORR in ALL patients is defined as the rate of complete remission (CR, CRh) on day 28.
- Being tested
- MB-CART19.1
- Keywords
- B cell Acute Lymphoblastic Leukemia, relapsed or refractory, CD-19 Positive
- Medical subject headings
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MB-CART19.1Drug
Also called Miltenyi CD-19 CAT-T cell
Miltenyi Biotec has established a semi-automated manufacturing process that can be made available to academic settings for systematic exploration of CAR strategies in advanced clinical studies. Closed-system operation, improved robustness, simplified work flows, and reduced labor intensity, while maintaining strict adherence to regulatory guidelines, allows for decentralized manufacturing. In this study, we will explore autologous 2nd generation CD19 CAR T cell products in patients with relapsed and refractory disease incurable with standard therapies.
| Study group | Role | What they receive |
|---|---|---|
| CRA treatment | Experimental | The drug for this trial is autologous T cells transduced with the lentiviral vector pLTG1563 (MB-CART19.1). The dose is 2x10e6 ~2x10e7 MB-CART19.1/kg.
A leukapheresis for the patient will be performed for MB-CART19.1 generation. All patients will receive lymphodepleting chemotherapy with fludarabine 30 mg/m2/d intravenously (iv) on days -5,-4,-3 and -2 cyclophosphamide 500 mg/m2/d iv on day -3,-2 before CAR T cell transfer to enhance the in vivo expansion of CAR T cells. Receives: Drug: MB-CART19.1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
ORR in ALL patients is defined as the rate of complete remission (CR, CRh) on day 28
Measured: 1 Month
Secondary outcomes (3)
Overall incidence and severity of adverse events.
Overall incidence and severity of adverse events will measure in this trial. Including: 1,Risks related to targeting of CD19+ normal B-cells; 2,Allergic reactions to CAR T cell infusion; 3, Cytokine release syndrome (CRS); 4, neurological toxicities; 5,Risks related to transfer of donor T cells after previous alloSCT; 6, Risks related to lentiviral gene transfer into human cells.
Measured: 1 Months
Rate of ALL patients achieving MRD negative CR
The rate of ALL patients achieving MRD negative CR in D28; 3,6,12months.
Measured: 12 Months
Relapse rate and time to relapse
Overall rate of relapse and the time to relapse from CART cell transfused.
Measured: 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2017
- Study start1 Dec 2017 (estimated)
- Primary completion1 Jul 2019 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Precursor B-Lymphoblastic Lymphoma/Leukaemia RefractoryStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Children's Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Miltenyi Biomedicine GmbH
- Responsible party
- Sponsor
- Investigators
- Jing Chen, MD,PhD, Principal investigator, Shanghai Children Medicine Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03321123
- Sponsor's protocol ID
- SCMC CART 20170920
- Status last verified
- Oct 2017
- First submitted
- 20 Sep 2017
- Last updated
- 25 Oct 2017
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Therapy With MB-CART19.1 in Patients With Relapsed/Refractory CD19-positive B Cell Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT03321123
- Acronym / sponsor ID
- SCMC CART 20170920
- Keywords
- B cell Acute Lymphoblastic Leukemia, relapsed or refractory, CD-19 Positive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Shanghai Children's Medical CenterUniversity, hospital or other
- Collaborators
- Miltenyi Biomedicine GmbH
- Study start
- 1 Dec 2017 (estimated)
- Primary completion
- 1 Jul 2019 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 25 Oct 2017 (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.
Precursor-B acute lymphoblastic leukemia (ALL) is the most common cancer in childhood. Despite major advances in ALL therapy, 20% of children and 40-50% of adults fail state-of-the art first-line treatment. But there is a strong need for alternative treatments to cure chemotherapy-refractory and relapsed B cell malignancies in pediatric patients. Relapsed and refractory B cell malignancies remain a therapeutic challenge, as these diseases are characterized by adverse survival. These cancers share a cell origin from the B-cell lineage and consequent surface expression of B-lineage markers such as CD19 and CD22. Chimeric antigen receptor (CAR) engineered T cell therapy has recently emerged as a new modality to target B cell malignancies. CARs couple a single-chain Fv (scFv) domain directed against a B-lineage-specific antigen to T-cell activating intracellular signaling domains. CAR gene-modified T cell interaction with target cells occurs in a HLA-independent fashion, so that a single vector can be used to treat all patients with cancers that express the target antigen. Miltenyi Biotec has established a semi-automated manufacturing process that can be made available to academic settings for systematic exploration of CAR strategies in advanced clinical studies. Closed-system operation, improved robustness, simplified work flows, and reduced labor intensity, while maintaining strict adherence to regulatory guidelines, allows for decentralized manufacturing. In the proposed phase II study, the investigator will explore autologous 2nd generation CD19 CAR T cell products in patients with relapsed and refractory disease incurable with standard therapies.
Detailed description
This is an open-label, non-randomized phase II paediatric study. In this study, eligible patients will receive autologous T cells transduced with the lentiviral vector pLTG1563 (MB-CART19.1) at a doesage of 2x10e6 ~2x10e7 CAR-transduced T cells/kg.
Upon enrollment, leukapheresis will be performed for MB-CART19.1 generation. Patients with high disease burden at screening (e.g. ALL with M3 marrow and 10.000/L blasts in peripheral blood) may receive bridging chemotherapy after leukapheresis, to avoid critical tumor lysis syndrome and cytokine release syndrome (CRS) by subsequent lymphodepleting chemotherapy and CAR transfer.
All patients will receive lymphodepleting chemotherapy with fludarabine 30 mg/m2/d intravenously (iv) on days -5,-4,-3 and -2 cyclophosphamide 500 mg/m2/d iv on day -3,-2 before CAR T cell transfer to enhance the in vivo expansion of CAR T cells.
Patients will receive freshly prepared MB-CART19.1 on day 0, corresponding to day 12 (48 hours) of manufacturing, at a dose of 2x10e6 ~2x10e7/kg MB-CART19.1 T cells as defined in the study design section. The appropriate volume for the target cell dose will be drawn up and given as an IV injection over 30 minutes through a large vein peripherally or centrally.
The primary objectives are:
- To assess the safety and tolerability of MB-CART19.1.
- To evaluate the biological activity of adoptive transfer of autologous MB-CART19.1 in patients with R/R CD19-positive B cell lymphoblastic leukemia.
The primary endpoint is Overall response rate (ORR):ORR in ALL patients is defined as the rate of complete remission (CR, CRh) on day 28.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CRA treatment | Experimental | Drug: MB-CART19.1The drug for this trial is autologous T cells transduced with the lentiviral vector pLTG1563 (MB-CART19.1). The dose is 2x10e6 ~2x10e7 MB-CART19.1/kg. A leukapheresis for the patient will be performed for MB-CART19.1 generation. All patients will receive lymphodepleting chemotherapy with fludarabine 30 mg/m2/d intravenously (iv) on days -5,-4,-3 and -2 cyclophosphamide 500 mg/m2/d iv on day -3,-2 before CAR T cell transfer to enhance the in vivo expansion of CAR T cells. |
Who may qualify
- Ages
- 2 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Age ≤18 years (if deemed fit by treating investigator)
- CD19 expression must be detected on the malignant cells by flow cytometry.
- Patients with relapsed disease with >5% blasts in BM (M2 or M3) after at least one standard chemotherapy and one salvage regimen who are ineligible for allogeneic stem cell transplant (alloSCT)
- Patients have refractory disease activity precluding alloSCT at this time, or patients who have relapsed post alloSCT at least 100 days post-transplant, with no evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
- Patients with combined extramedullary ALL are eligible if extramedullary disease has been successfully cleared by conventional therapy at the time of inclusion (e.g. intrathecal chemotherapy, orchiectomy). This includes patients with combined CNS-2 (<5 WBC/µl CSF, with blasts on cytospin) or CNS-3 (5WBC/µl CSF, with blasts on cytospin) disease and patients with combined testicular relapse.
Key exclusion criteria (8 listed)
- Rapidly progressive disease that in the estimation of live less than 12 weeks
- Isolated extramedullary relapse (CNS and/or testicular) in ALL
- Current autoimmune disease, or history of autoimmune disease with potential CNS involvement
- Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis)
- History of an additional malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease free for ≥3 years.
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 |
|---|---|---|
| MB-CART19.1Also: Miltenyi CD-19 CAT-T cellMiltenyi Biotec has established a semi-automated manufacturing process that can be made available to academic settings for systematic exploration of CAR strategies in advanced clinical studies. Closed-system operation, improved robustness, simplified work flows, and reduced labor intensity, while maintaining strict adherence to regulatory guidelines, allows for decentralized manufacturing. In this study, we will explore autologous 2nd generation CD19 CAR T cell products in patients with relapsed and refractory disease incurable with standard therapies. | Drug | CRA treatment |
Primary outcome
Overall response rate
Time frame: 1 Month
ORR in ALL patients is defined as the rate of complete remission (CR, CRh) on day 28
3 secondary outcomes
Overall incidence and severity of adverse events.
Time frame: 1 Months
Rate of ALL patients achieving MRD negative CR
Time frame: 12 Months
Relapse rate and time to relapse
Time frame: 12 Months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2017.
- Individual participant dataSharing planned: Undecided
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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.
Jing Chen, MD,PhD principal investigator
Shanghai Children Medicine Center
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MB-CART19.1 in people with Precursor B-Lymphoblastic Lymphoma/Leukaemia Refractory, run by Shanghai Children's Medical Center.
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 6 inclusion and 8 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 25 Oct 2017. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Jing Chen, MD, PhD (86 18930830632, chenjing@scmc.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (time frame: 1 Month). 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 Oct 2017.