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MB-CART19.1 r/r CD19+ B-cell Malignancies (BCM)

Primary Purpose

Acute Lymphoblastic Leukemia Recurrent, B-cell Lymphoma Recurrent, B-cell Lymphoma Refractory

Status
Recruiting
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
MB-CART19.1
Sponsored by
Miltenyi Biomedicine GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia Recurrent

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female patients must have r/r CD19-expressing ALL or NHL/CLL
  • CD19 expression must be detected on the malignant cells by flow cytometry (leukemia, malignant effusion in NHL) or immunohistochemistry (NHL);
  • Age ≥ 1 year (if deemed fit by treating investigator);
  • Absolute CD3+ T cell count ≥100/μl;
  • ECOG performance score of 0-2 if >16 years old, or Lansky performance score of >50 if ≤16 years old at screening;
  • No active Hepatitis B, Hepatitis C, HIV1/2;
  • No childbearing potential or negative pregnancy test at screening and before chemotherapy in women with childbearing potential;
  • Signed and dated informed consent/assent by patients
  • and meet the following disease-specific criteria:

ALL:

  • patients 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) or have refractory disease activity precluding alloSCT at this time, or
  • patients who have relapsed post alloSCT at least 100 days posttransplant, with no evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
  • patients with Ph+ ALL if they are intolerant to tyrosine kinase inhibitor (TKI) therapy, or if they have r/r disease after treatment with at least 2 different TKIs.
  • ALL patients with combined bone marrow and CNS and/or testicular relapse are eligible only if the extramedullary disease has been successfully cleared by conventional therapy at the time of inclusion (e.g. intrathecal chemotherapy, orchiectomy).

Pediatric aggressive NHL (1-17 years):

  • patients after at least one salvage chemotherapy as bridge to alloSCT or
  • patients ineligible for alloSCT or
  • patients who have relapsed post alloSCT at least 100 days posttransplant, with not evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
  • patients with CNS disease (excluding isolated CNS lymphoma) are eligible only if disease has been successfully cleared by intrathecal chemotherapy at the time of inclusion.

Adult NHL:

  • patients after at least one standard chemotherapy and one salvage regimen as bridge to alloSCT or
  • patients who are ineligible for alloSCT or
  • patients who have relapsed post alloSCT at least 100 days posttransplant, with no evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
  • patients with CNS disease (excluding isolated CNS lymphoma) are eligible only if disease has been successfully cleared by intrathecal chemotherapy at the time of inclusion.

CLL:

  • patients with r/r disease after established and approved treatment options have failed.
  • patients not eligible or appropriate for conventional alloSCT.

Exclusion Criteria:

  • Isolated CNS or testicular relapse in ALL;
  • Isolated CNS lymphomas;
  • Active solid brain metastases or history of solid brain metastases
  • 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 or an oxygen requirement of >28% O2 supplementation or active pulmonary infiltrates on chest X-ray;
  • Cardiac function: Fractional shortening <28% or left ventricular ejection fraction <50% by echocardiography;
  • Renal function: GFR ≤29 mL/min/1.73 m2 by CKD-EPI for patients 18 yrs (Levey et al. 2009) or creatinine clearance ≤29 mL/min/1.73 m2 by Schwartz formula (Schwartz et al. 1976) for patients <18 yrs of age;
  • Liver function: Patients with a serum bilirubin >3 times upper limit of normal or an AST or ALT > 5 times upper limit of normal, unless due to leukemic liver infiltration in the estimation of the investigator;
  • Rapidly progressive disease that in the estimation of the investigator would compromise ability to complete study therapy;
  • Pregnant or breast-feeding females;
  • Medications:

    • Systemic chemotherapies, corticosteroids with the exception of physiologic replacement dosing, tyrosine kinase inhibitors (TKI) within 7 days prior to leukapheresis,
    • Fludarabine/clofarabine or immunosuppressive drugs and antibodies (e.g. rituximab, calcineurin inhibitors, blinatumomab) or investigational drugs or donor lymphocyte transfusions or radiation therapy within 30 days prior to apheresis,
    • Alemtuzumab within 3 months prior to leukapheresis,
    • Exception: Intrathecal chemotherapy is allowed prior to treatment, but should be discontinued in ALL and BL 10 days prior to MB-CART19.1 infusion to limit risk of neurotoxicities;
  • 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;
  • Intake of concomitant medication contraindicated for other reasons than hypersensitivity, e.g. live vaccines and fludarabine;
  • Contraindication of trial related procedures as judged by the investigator, e.g. lumbar punctures for CSF sampling;
  • Female patients of child-bearing potential not willing to practice a highly effective form of birth control from the time of enrollment and for 12 months after dosing the IMP;
  • Male patients of fathering potential not willing to practice a highly effective form of birth control from the time of enrollment and for 12 months after dosing the IMP;
  • Concurrent participation in another interventional trial that could interact with this trial, e.g. CAR T trials;
  • Cerebral dysfunction, legal incapacity of adult patients;
  • Committal to an institution on judicial or official order.

Sites / Locations

  • Charité - University clinic, pediatric clinic with focus on oncology and hematologyRecruiting
  • University clinic, clinical for children and youth
  • Universitätsklinikum ErlangenRecruiting
  • University medicine Goettingen, Clinic of hematology and medical oncologyRecruiting
  • Children's Hospital of Dr. von Hauner by Ludwig-Maximilian UniversityRecruiting
  • Universitätsklinikum Münster - Klink für Kinderheilkunde und Jugendmedizin / Pädiatrische Hämatologie und OnkologieRecruiting
  • Universitätsklinikum Münster - Medizinische Klinik A / KMT ZentrumRecruiting
  • Tuebingen University clinic, medical university clinic for internal medicineRecruiting
  • University clinic for children and youth medicine
  • University clinic, pediatric hematology and oncologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase I: DL 0: 1x10e5 MB-CART19.1 cells

Phase I: DL 1: 5x10e5 MB-CART19.1 cells

Phase I: DL 2: 1x10e6 MB-CART19.1 cells

Phase I: DL 3: 3x10e6 MB-CART19.1 cells

Phase II - Recommended dose MB-CART19.1

Arm Description

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.

Dose evaluation will start in Cohorts 1 and 2 with Dose Level 1. 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.

Dose evaluation will start in Cohort 3 with Dose Level 2, sparing Dose Level 1. If Dose Level 2 is not tolerated, Dose Level 1 will be tested. 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 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.

Phase II will evaluate the efficacy and safety in patients treated with the recommended dose in Cohorts 1 to 3, respectively.

Outcomes

Primary Outcome Measures

Phase I - Determination of the recommended dose of MB-CART19.1
Determined on the basis of the maximum tolerated dose (MTD); MTD is defined as the highest dose level at which < 33% of patients experience Dose Limiting Toxicity (DLT). Safety and toxicity assessment of MB-CART19.1 per adverse events (AE) reporting classified according to CTCAE version 5.0
Phase II - Determination of the Overall Response Rate (ORR)
ORR in ALL patients is defined as the rate of complete remission (CR, CRh); ORR in NHL patients is defined as the rate of overall response (CR or PR)

Secondary Outcome Measures

Phase I - Overall incidence and severity of adverse events
per adverse events (AE) reporting classified according to CTCAE version 5.0
Phase I - Response to treatment for each timepoint
ORR in ALL (Rate of CR/CRh)
Phase I - Response to treatment for each timepoint
Rate MRD-negative CR in ALL
Phase I - Response to treatment for each timepoint
ORR in NHL/CLL (Rate of CR/PR)
Phase I - Occurence of B-cell depletion
Circulating B cell numbers
Phase I - Phenotype and persistence of MB-CART19.1
Blood samples for determination of persistence/phenotyping of infused MB-CART19.1 will be analysed.
Phase II - Overall incidence and severity of adverse events
per adverse events (AE) reporting classified according to CTCAE version 5.0
Phase II - Number of patients with successful MB-CART19.1 production
Number of patients meeting the inclusion criteria and none of the exclusion criteria for who an autologous MB-CART19.1 product can be generated
Phase II - Rate of ALL patients achieving MRD negative CR
Rate MRD-negative CR in ALL
Phase II - Duration of response
Determination of response rate
Phase II - Disease-free survival
Determination of survival and relapse
Phase II - Occurrence of B cell depletion
Circulating B cell numbers in the peripheral blood will be assessed by Flow cytometry.
Phase II - Phenotype and persistence of MB-CART19.1
Blood samples for determination of persistence/phenotyping of infused MB-CART19.1 will be analysed.

Full Information

First Posted
February 19, 2019
Last Updated
November 30, 2021
Sponsor
Miltenyi Biomedicine GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT03853616
Brief Title
MB-CART19.1 r/r CD19+ B-cell Malignancies (BCM)
Official Title
A Phase I/II Safety, Dose Finding and Feasibility Trial of MB-CART19.1 in Patients With Relapsed or Refractory CD19 Positive B Cell Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
November 26, 2018 (Actual)
Primary Completion Date
August 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Miltenyi Biomedicine GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a phase l/ll multi-centric, 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. The trial consists of 2 parts: Part I and Part II. In total approximately 48 patients will be included in Part I of the trial. 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 Part I (Phase I) will evaluate the safety of the MB-CART19.1 and determine the recommended dose levels for the Part II (Phase II) efficacy evaluation in each of the three disease cohorts. Dose evaluation will start in Cohorts 1 and 2 with Dose Level 1 and in Cohort 3 with Dose Level 2, sparing Dose Level 1 (see figure 1). Each of the cohorts will evaluate the safety of MB-CART19.1. 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. Cohort 3 will Start with Dose Level 2. If Dose Level 2 is not tolerated, Dose Level 1 will be tested. DLT will be evaluated within 4 weeks after the infusion of MB-CART19.1. An interval of at least 28 days between the treatment of the first and the second patient in each dose level (and in each cohort) is mandatory. Part II (Phase II) will evaluate the efficacy and safety in patients treated with the recommended dose in Cohorts 1 to 3, respectively. After review of completed day 28 safety and efficacy data within Part I (Phase I) by the SMB, the design of Phase II, specifically the number and types of Phase II cohorts and the recommended dose level(s) for Phase II will be determined and thus, the number of patients to be treated will be calculated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia Recurrent, B-cell Lymphoma Recurrent, B-cell Lymphoma Refractory, Chronic Lymphocytic Leukemia Recurrent, Chronic Lymphocytic Leukemia Refractory

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase I: DL 0: 1x10e5 MB-CART19.1 cells
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase I: DL 1: 5x10e5 MB-CART19.1 cells
Arm Type
Experimental
Arm Description
Dose evaluation will start in Cohorts 1 and 2 with Dose Level 1. 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.
Arm Title
Phase I: DL 2: 1x10e6 MB-CART19.1 cells
Arm Type
Experimental
Arm Description
Dose evaluation will start in Cohort 3 with Dose Level 2, sparing Dose Level 1. If Dose Level 2 is not tolerated, Dose Level 1 will be tested. 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.
Arm Title
Phase I: DL 3: 3x10e6 MB-CART19.1 cells
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase II - Recommended dose MB-CART19.1
Arm Type
Experimental
Arm Description
Phase II will evaluate the efficacy and safety in patients treated with the recommended dose in Cohorts 1 to 3, respectively.
Intervention Type
Biological
Intervention Name(s)
MB-CART19.1
Other Intervention Name(s)
CD19-targeting CAR T cells, Anti-CD19 CAR T cells
Intervention Description
MB-CART19.1 consists of autologous CD19 Chimeric Antigen Receptor (CAR) transduced CD4/CD8 enriched T cells targeting CD19-positive tumor cells in b cell malignancies
Primary Outcome Measure Information:
Title
Phase I - Determination of the recommended dose of MB-CART19.1
Description
Determined on the basis of the maximum tolerated dose (MTD); MTD is defined as the highest dose level at which < 33% of patients experience Dose Limiting Toxicity (DLT). Safety and toxicity assessment of MB-CART19.1 per adverse events (AE) reporting classified according to CTCAE version 5.0
Time Frame
until day 28 after infusion of MB-CART19.1
Title
Phase II - Determination of the Overall Response Rate (ORR)
Description
ORR in ALL patients is defined as the rate of complete remission (CR, CRh); ORR in NHL patients is defined as the rate of overall response (CR or PR)
Time Frame
28 days after infusion of MB-CART19.1 (and at month 3 in NHL patients not in CR on day 28)
Secondary Outcome Measure Information:
Title
Phase I - Overall incidence and severity of adverse events
Description
per adverse events (AE) reporting classified according to CTCAE version 5.0
Time Frame
throug study completion, an average of 5 years
Title
Phase I - Response to treatment for each timepoint
Description
ORR in ALL (Rate of CR/CRh)
Time Frame
day 28
Title
Phase I - Response to treatment for each timepoint
Description
Rate MRD-negative CR in ALL
Time Frame
day 28, week 12, month 6, 1 year
Title
Phase I - Response to treatment for each timepoint
Description
ORR in NHL/CLL (Rate of CR/PR)
Time Frame
day 28, patients not in CR on day 28: month 3
Title
Phase I - Occurence of B-cell depletion
Description
Circulating B cell numbers
Time Frame
through study completion, an average of 5 years
Title
Phase I - Phenotype and persistence of MB-CART19.1
Description
Blood samples for determination of persistence/phenotyping of infused MB-CART19.1 will be analysed.
Time Frame
days 2, 7, 10, 14, 28, weeks 8, 12, months 6, 12, 24, 36, 48, 60
Title
Phase II - Overall incidence and severity of adverse events
Description
per adverse events (AE) reporting classified according to CTCAE version 5.0
Time Frame
through study completion, an average of 5 years
Title
Phase II - Number of patients with successful MB-CART19.1 production
Description
Number of patients meeting the inclusion criteria and none of the exclusion criteria for who an autologous MB-CART19.1 product can be generated
Time Frame
day 0
Title
Phase II - Rate of ALL patients achieving MRD negative CR
Description
Rate MRD-negative CR in ALL
Time Frame
day 28, week 12, month 6, 1 year
Title
Phase II - Duration of response
Description
Determination of response rate
Time Frame
through study completion, an average of 5 years
Title
Phase II - Disease-free survival
Description
Determination of survival and relapse
Time Frame
at 1 year after MB-CART19.1 infusion in patients not receiving alloSCT
Title
Phase II - Occurrence of B cell depletion
Description
Circulating B cell numbers in the peripheral blood will be assessed by Flow cytometry.
Time Frame
days 7, 10, 14, 28, weeks 8, 12, 16, months 6, 8, 10, 12, 24, 36, 48, 60
Title
Phase II - Phenotype and persistence of MB-CART19.1
Description
Blood samples for determination of persistence/phenotyping of infused MB-CART19.1 will be analysed.
Time Frame
days 2, 7, 10, 14, 28, weeks 8, 12, months 6, 12, 24, 36, 48, 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients must have r/r CD19-expressing ALL or NHL/CLL CD19 expression must be detected on the malignant cells by flow cytometry (leukemia, malignant effusion in NHL) or immunohistochemistry (NHL); Age ≥ 1 year (if deemed fit by treating investigator); Absolute CD3+ T cell count ≥100/μl; ECOG performance score of 0-2 if >16 years old, or Lansky performance score of >50 if ≤16 years old at screening; No active Hepatitis B, Hepatitis C, HIV1/2; No childbearing potential or negative pregnancy test at screening and before chemotherapy in women with childbearing potential; Signed and dated informed consent/assent by patients and meet the following disease-specific criteria: ALL: patients 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) or have refractory disease activity precluding alloSCT at this time, or patients who have relapsed post alloSCT at least 100 days posttransplant, with no evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment. patients with Ph+ ALL if they are intolerant to tyrosine kinase inhibitor (TKI) therapy, or if they have r/r disease after treatment with at least 2 different TKIs. ALL patients with combined bone marrow and CNS and/or testicular relapse are eligible only if the extramedullary disease has been successfully cleared by conventional therapy at the time of inclusion (e.g. intrathecal chemotherapy, orchiectomy). Pediatric aggressive NHL (1-17 years): patients after at least one salvage chemotherapy as bridge to alloSCT or patients ineligible for alloSCT or patients who have relapsed post alloSCT at least 100 days posttransplant, with not evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment. patients with CNS disease (excluding isolated CNS lymphoma) are eligible only if disease has been successfully cleared by intrathecal chemotherapy at the time of inclusion. Adult NHL: patients after at least one standard chemotherapy and one salvage regimen as bridge to alloSCT or patients who are ineligible for alloSCT or patients who have relapsed post alloSCT at least 100 days posttransplant, with no evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment. patients with CNS disease (excluding isolated CNS lymphoma) are eligible only if disease has been successfully cleared by intrathecal chemotherapy at the time of inclusion. CLL: patients with r/r disease after established and approved treatment options have failed. patients not eligible or appropriate for conventional alloSCT. Exclusion Criteria: Isolated CNS or testicular relapse in ALL; Isolated CNS lymphomas; Active solid brain metastases or history of solid brain metastases 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 or an oxygen requirement of >28% O2 supplementation or active pulmonary infiltrates on chest X-ray; Cardiac function: Fractional shortening <28% or left ventricular ejection fraction <50% by echocardiography; Renal function: GFR ≤29 mL/min/1.73 m2 by CKD-EPI for patients 18 yrs (Levey et al. 2009) or creatinine clearance ≤29 mL/min/1.73 m2 by Schwartz formula (Schwartz et al. 1976) for patients <18 yrs of age; Liver function: Patients with a serum bilirubin >3 times upper limit of normal or an AST or ALT > 5 times upper limit of normal, unless due to leukemic liver infiltration in the estimation of the investigator; Rapidly progressive disease that in the estimation of the investigator would compromise ability to complete study therapy; Pregnant or breast-feeding females; Medications: Systemic chemotherapies, corticosteroids with the exception of physiologic replacement dosing, tyrosine kinase inhibitors (TKI) within 7 days prior to leukapheresis, Fludarabine/clofarabine or immunosuppressive drugs and antibodies (e.g. rituximab, calcineurin inhibitors, blinatumomab) or investigational drugs or donor lymphocyte transfusions or radiation therapy within 30 days prior to apheresis, Alemtuzumab within 3 months prior to leukapheresis, Exception: Intrathecal chemotherapy is allowed prior to treatment, but should be discontinued in ALL and BL 10 days prior to MB-CART19.1 infusion to limit risk of neurotoxicities; 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; Intake of concomitant medication contraindicated for other reasons than hypersensitivity, e.g. live vaccines and fludarabine; Contraindication of trial related procedures as judged by the investigator, e.g. lumbar punctures for CSF sampling; Female patients of child-bearing potential not willing to practice a highly effective form of birth control from the time of enrollment and for 12 months after dosing the IMP; Male patients of fathering potential not willing to practice a highly effective form of birth control from the time of enrollment and for 12 months after dosing the IMP; Concurrent participation in another interventional trial that could interact with this trial, e.g. CAR T trials; Cerebral dysfunction, legal incapacity of adult patients; Committal to an institution on judicial or official order.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alisa Yakushina
Phone
+4916098973562
Email
Alisa.yakushina@miltenyi.com
First Name & Middle Initial & Last Name or Official Title & Degree
Christine Schubert
Phone
+49 2204 8306 6564
Email
christine.schubert@miltenyi.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudia Rössig, Prof. Dr.
Organizational Affiliation
Univeristy Hospital Muenster
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charité - University clinic, pediatric clinic with focus on oncology and hematology
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Annette Kuenkele, Dr.
Phone
+49 30 450 616 178
Email
annette.kuenkele@charite.de
First Name & Middle Initial & Last Name & Degree
Arend von Stackelberg, PD, Dr.
Phone
+49 30 450 666 833
Email
arend.stackelberg@charite.de
Facility Name
University clinic, clinical for children and youth
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Universitätsklinikum Erlangen
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreas Mackensen, Prof.Dr.
Phone
0049 (0)9131 8535 954
Email
andreas.mackensen@uk-erlangen.de
First Name & Middle Initial & Last Name & Degree
Barbara Ferstl, Dr.
Phone
0049 (0)9131 8543 104
Email
barbara.ferstl@uk-erlangen.de
Facility Name
University medicine Goettingen, Clinic of hematology and medical oncology
City
Göttingen
ZIP/Postal Code
37075
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Justin Hasenkamp, Dr.
Phone
+49 55 139 651 82
Email
justin.hasenkamp@med.uni-goettingen.de
First Name & Middle Initial & Last Name & Degree
Gerald Wulf, Prof., Dr.
Phone
+49 55 139 170 577
Email
gerald.wulf@med.uni-goettingen.de
Facility Name
Children's Hospital of Dr. von Hauner by Ludwig-Maximilian University
City
Munich
ZIP/Postal Code
80337
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tobias Feuchtinger, Prof., Dr.
Phone
+49 89 440 052 759
Email
tobias.feuchtinger@med.uni-muenchen.de
First Name & Middle Initial & Last Name & Degree
Vera Binder, Dr.
Phone
+49 89 440 052 875
Email
vera.binder@med.uni-muenchen.de
Facility Name
Universitätsklinikum Münster - Klink für Kinderheilkunde und Jugendmedizin / Pädiatrische Hämatologie und Onkologie
City
Münster
ZIP/Postal Code
48149
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claudia Rössig, Prof. Dr.
Phone
0049 (0)251 83 47 741
Email
rossig@ukmuenster.de
First Name & Middle Initial & Last Name & Degree
Birgit Burkhardt, PD Dr.
Phone
0049 (0)251 83 52 840
Email
birgit.burkhardt@ukmuenster.de
Facility Name
Universitätsklinikum Münster - Medizinische Klinik A / KMT Zentrum
City
Münster
ZIP/Postal Code
48149
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthias Stelljes, Prof. Dr.
Phone
+49 251 83 52801
Email
matthias.stelljes@ukmuenster.de
First Name & Middle Initial & Last Name & Degree
Jan Henrik Mikesch, Dr.
Phone
+49 251 83 52801
Email
jan-henrik.mikesch@ukmuenster.de
Facility Name
Tuebingen University clinic, medical university clinic for internal medicine
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wolfgang Bethge, Prof., Dr.
Phone
+49 70 712 083 176
Email
wolfgang.bethge@med.uni-tuebingen.de
First Name & Middle Initial & Last Name & Degree
Christoph Faul, Dr.
Phone
+49 70 712 984 087
Email
christoph.faul@med.uni-tuebingen.de
Facility Name
University clinic for children and youth medicine
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
University clinic, pediatric hematology and oncology
City
Würzburg
ZIP/Postal Code
97070
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul-Gerhardt Schlegel, Prof., Dr.
Phone
+49 93 120 127 999
Email
schlegel_p@ukw.de
First Name & Middle Initial & Last Name & Degree
Eyrich Matthias, Prof., Dr.
Phone
+49 93 120 127 620
Email
eyrich_m@ukw.de

12. IPD Sharing Statement

Plan to Share IPD
No

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MB-CART19.1 r/r CD19+ B-cell Malignancies (BCM)

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