MB-CART19.1 r/r CD19+ BCM
- Conditions
- Relapsed or refractory CD19 positive B cell malignancies (pediatric acute lymphatic leukemia [ALL], aggressive NHL)Relapsed or refractory CD19 positive B cell malignancies (adult ALL, adult NHL/chronic lymphatic leukemia [CLL])Refractory/relapsed B-NHL
- Registration Number
- 2024-513334-38-00
- Lead Sponsor
- Miltenyi Biomedicine GmbH
- Brief Summary
The objective of this trial is to assess feasibility, safety and efficacy of ex vivo generated MB-CART19.1 in patients with relapsed or refractory CD19 positive B cell malignancies.
Phase I Primary objective: To determine the recommended dose of MB-CART19.1.
Phase II Primary objective: To assess the response to adoptive cell therapy using autologous MBCART19.1.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 49
Male or female patients must have r/r CD19-expressing ALL or NHL/CLL and meet the following disease-specific criteria: All Cohorts: 1a) 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 1b) patients who have relapsed post alloSCT no earlier than 100 days posttransplant, with no evidence of active GVHD, and not taking immunosuppressive agents for at least 30 days prior to leukapheresis. 1c) 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. 1d) 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): 1e) patients after at least one salvage chemotherapy as bridge to alloSCT or 1f) patients ineligible for alloSCT or 1g) patients who have relapsed post alloSCT no earlier than 100 days posttransplant, with not evidence of active GVHD, and not taking immunosuppressive agents for at least 30 days prior to leukapheresis. 1h) 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: 1i) patients after at least one standard chemotherapy and one salvage regimen as bridge to alloSCT or 1j) patients who are ineligible for alloSCT or 1k) patients who have relapsed post alloSCT no earlier than 100 days posttransplant, with no evidence of active GVHD, and not taking immunosuppressive agents for at least 30 days prior to leukapheresis. 1l) 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: 1m) patients with r/r disease after established and approved treatment options have failed. 1n) patients not eligible or appropriate for conventional alloSCT.
CD19 expression must be detected on the malignant cells by flow cytometry (leukemia, malignant effusion in NHL) or immunohistochemistry (NHL). Results of previous assessments after the last treatment with CD19 targeted therapies but preceding inclusion of the patient in this trial are acceptable, if available;
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/or parents, before conduct of any trial-specific procedure.
Isolated CNS or testicular relapse in ALL
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: a. Systemic chemotherapies, corticosteroids with the exception of physiologic replacement dosing, tyrosine kinase inhibitors (TKI) and other kinase inhibitors (e.g. ibrutinib) within 7 days prior to leukapheresis; b. Fludarabine/clofarabine or immunosuppressive drugs and antibodies (e.g. rituximab, calcineurin inhibitors, blinatumomab) or donor lymphocyte transfusions or radiation therapy within 14 days prior to leukapheresis, c. Previous treatment with CAR T cells (e.g. Kymriah®), d. Alemtuzumab within 3 months prior to leukapheresis, e. Exception: Intrathecal chemotherapy is allowed until 8 days prior to leukapheresis, with the exception of cytarabine. After leukapheresis, a single dose of intrathecal chemotherapy is allowed but should be discontinued 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
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
BMI ≥ 30
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: Pediatric patients: fractional shortening <28% or left ventricular ejection fraction <50% by echocardiography, adult patients: left ventricular ejection fraction <50% by echocardiography
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Phase I: Recommended dose of MB-CART19.1, determined on the basis of the maximum tolerated dose (MTD), defined as the highest dose level of the two to three dose levels tested at which <33% of patients experience DLT until day 28 after infusion of MB-CART19.1, and on the basis of the safety and efficacy data. Phase I: Recommended dose of MB-CART19.1, determined on the basis of the maximum tolerated dose (MTD), defined as the highest dose level of the two to three dose levels tested at which <33% of patients experience DLT until day 28 after infusion of MB-CART19.1, and on the basis of the safety and efficacy data.
Phase I: Safety and toxicity assessment of MB-CART19.1 per adverse events (AE) reporting classified according to CTCAE version 5.0. defined by <33% of patients experiencing DLT, or maximal administered dose. Phase I: Safety and toxicity assessment of MB-CART19.1 per adverse events (AE) reporting classified according to CTCAE version 5.0. defined by <33% of patients experiencing DLT, or maximal administered dose.
Phase II: Determination of the Overall Response Rate (ORR) Phase II: Determination of the Overall Response Rate (ORR)
Phase II: ORR in ALL patients as defined above on day 28 Phase II: ORR in ALL patients as defined above on day 28
Phase II: ORR in NHL patients as defined above on day 28 and month 3. Phase II: ORR in NHL patients as defined above on day 28 and month 3.
- Secondary Outcome Measures
Name Time Method Phase I: Overall incidence and severity of adverse events Phase I: Overall incidence and severity of adverse events
Phase I: Response to treatment: o Overall response rate (ORR) in ALL patients defined as the rate of complete remission (CR, CRh) on day 28; o Rate of ALL patients achieving MRD response (<10-4); o ORR in NHL patients is defined as the rate of overall response (CR or PR) on day 28 and at month 3 in patients not in CR on day 28 Phase I: Response to treatment: o Overall response rate (ORR) in ALL patients defined as the rate of complete remission (CR, CRh) on day 28; o Rate of ALL patients achieving MRD response (<10-4); o ORR in NHL patients is defined as the rate of overall response (CR or PR) on day 28 and at month 3 in patients not in CR on day 28
Phase I: Occurrence of B cell depletion Phase I: Occurrence of B cell depletion
Phase I: Phenotype and persistence of MB-CART19.1 Phase I: Phenotype and persistence of MB-CART19.1
Phase I: Further safety assessments. Phase I: Further safety assessments.
Phase II: Safety and toxicity of MB-CART19.1 per adverse events (AE) reporting classified according to CTCAE version 5.0; Phase II: Safety and toxicity of MB-CART19.1 per adverse events (AE) reporting classified according to CTCAE version 5.0;
Phase II: Proportion 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: Proportion 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 response (<10-4) Phase II: Rate of ALL patients achieving MRD response (<10-4)
Phase II: Duration of response, relapse rate and time to relapse; Phase II: Duration of response, relapse rate and time to relapse;
Phase II: Disease-free and overall survival at 1 year after adoptive immunotherapy with MB-CART19.1 in patients not receiving alloSCT; Phase II: Disease-free and overall survival at 1 year after adoptive immunotherapy with MB-CART19.1 in patients not receiving alloSCT;
Phase II: Occurrence of B cell depletion; Phase II: Occurrence of B cell depletion;
Phase II: Phenotype and persistence of MB-CART19.1. Phase II: Phenotype and persistence of MB-CART19.1.
Trial Locations
- Locations (6)
Universitaetsmedizin Goettingen
🇩🇪Goettingen, Germany
Klinikum der Universitaet Muenchen AöR
🇩🇪Munich, Germany
Universitaetsklinikum Muenster AöR
🇩🇪Muenster, Germany
Charite Universitaetsmedizin Berlin KöR
🇩🇪Berlin, Germany
Universitaetsklinikum Erlangen AöR
🇩🇪Erlangen, Germany
Universitaetsklinikum Tuebingen AöR
🇩🇪Tuebingen, Germany
Universitaetsmedizin Goettingen🇩🇪Goettingen, GermanyJustin HasenkampSite contact00495513965182justin.hasenkamp@med.uni-goettingen.de