A Phase I Trial to Establish the Safety and Maximum Tolerated Dose of High-affinity Autologous BCMA-targeting Chimeric Antigen Receptor (CAR) T-cells in Patients With Relapsed and Refractory B-cell Malignancies

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

Studienbeginn:
Februar 2024

Letztes Update:
20.02.2024

Wirkstoff:
-

Indikation (Clinical Trials):
Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Technische Universität Dresden

Collaborator:
German Cancer Research Center

Studienleiter

Martin Wermke, Prof.
Principal Investigator
Technische Universität Dresden (TUD)

Kontakt

Martin Wermke, Prof.
Kontakt:
Phone: +49 351 458 13408
E-Mail: carlotta@ukdd.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Technische Universität Dresden, NCT/UCC, Early Clinical Trial Unit
01307 Dresden
(Sachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Martin Wermke, Prof.» Ansprechpartner anzeigen

Studien-Informationen

Brief Summary:

The purpose of this phase I study is to determine whether MDC-CAR-BCMA001 (BCMA directed CAR

T-cells) is safe and tolerable in the treatment of relapsed and refractory B-cell

malignancies

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Male or female patients aged ≥ 18 years

- Written informed consent of the subject

- Able and willing to adhere to the trial protocol

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Either Multiple Myeloma (MM):

1. relapsed or refractory disease after at least 2 lines of treatment including an

Immunomodulatory drug, a proteasome inhibitor and an anti-cluster of

differentiation 38 antibody or anti-cluster of differentiation 319 (SLAMF7;

Elotuzumab) antibody AND

2. not eligible for treatment with other regimen available according to local

standard of care and known to confer clinical benefit according to the

investigator's discretion, prior treatment with other BCMA-targeting

immunotherapies (including T-cell engaging antibodies, CAR T-cells and

antibody-drug immuno-conjugates) is allowed AND

3. measurable disease defined by serum M-Protein ≥ 10 g/l OR urine M-Protein ≥ 200

mg/24h OR serum free light chain > 100 mg/l of involved free light chain and

abnormal serum free light chain ratio

OR

Diffuse large B-cell lymphoma (DLBCL):

4. Relapsed after or refractory to standard curative therapy (such as R-CHOP) and

refractory to at least one course of standard salvage chemotherapy OR

5. Relapsed within one year after high-dose chemotherapy and autologous stem cell

support OR

6. Relapsed after allogeneic stem-cell transplantation or approved anti-cluster of

differentiation 19 CAR T-cell therapies.

AND (applicable to all DLBCL patients)

7. Not be eligible for treatment with other regimen available according to local

standard of care and known to confer clinical benefit. This includes but is not

limited to anti-cluster of differentiation 19 directed CAR T-cell therapies with

approved constructs AND (applicable to all DLBCL patients)

8. Measurable disease according to Lugano criteria

- Adequate organ function defined as:

1. Neutrophils ≥ 0.5 Gpt/l and Platelets ≥ 50 Gpt/l (unless due to subtotal

infiltration of the bone marrow by underlying malignancy)

2. Lymphocytes ≥ 0.1 Gpt/l

3. Alaninaminotransferase and Asparataminotransferase ≤ 3.0x Upper limit of normal

4. Bilirubin ≤ 1.5x Upper limit of normal

5. Creatinine ≤ 1.5x Upper limit of normal

6. Adequate cardiac function i.e. left ventricular ejection fraction ≥ 50%, no major

valve abnormalities or dyskinesias

- A female of childbearing potential* may be enrolled providing she has a negative

pregnancy test at screening and is routinely using a highly effective method of birth

control (pearl index of ≤ 1 required) resulting in a low failure rate (e.g. hormonal

contraception, intrauterine device, total sexual abstinence or sterilization). Male

patients must also prac-tice a highly effective method of birth control and should not

father a child at least until 12 months after infusion of CAR T-cells

Exclusion Criteria:

- Any Central nervous system (CNS)-involvement by underlying disease

- History of seizure or cerebrovascular ischemia / hemorrhage within the last 12 months

- History of any autoimmune Central nervous system disease (e.g. multiple sclerosis,

amyotrophic lateral sclerosis, optic neuritis)

- Ongoing neurologic conditions that in the opinion of the investigator might increase

the risk for neurotoxicity or impair the assessment of CAR-associated neurotoxicity

- Inadequate pulmonary function (i.e. need for continuous oxygen support)

- Patients on hemodialysis

- Any contraindications to Fludarabine and/or Cyclophosphamide as given in the Summary

of product characteristics

- Any other active malignancy requiring active treatment or interfering with the

assessment of primary or secondary trial endpoints, adjuvant hormonal therapy is

allowed

- Positivity for anti-human immunodeficiency virus (HIV) immunoglobulin

- Active or chronic infectious hepatitis B (HBV) and C (HCV) virus unless serology

demonstrates clearance of infection (i.e. Polymerase chain reaction undetectable viral

load for hepatitis)

- Active infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) or

history of SARS-CoV2 infection within the past 3 months or active long coronavirus

disease (COVID) syndrome

- Uncontrolled bacterial, viral or fungal infections defined as infections needing

in-patient and/or i.v. antimicrobial treatment*

- Active Graft versus Host Disease defined as active symptoms of graft-versus-host

disease or ongoing immunosuppressive treatment or prophylaxis within the last 30 days

prior to application of MDC-CAR-BCMA001

- Psychologic disorders, drug abuse or any other condition which might significantly

impair a patient's ability to comply with the trial protocol

- Patients who are expected to deteriorate during the time needed for manufacturing

MDC-CAR-BCMA001 in spite of bridging therapy in the opinion of the investigator

including

- Any condition requiring systemic treatment with immunosuppressive drugs (including but

not limited to steroids exceeding 20 mg Prednisolone per day)

- Any antineoplastic treatment within 7 days prior to leukapheresis or within 2 weeks or

5 half-lives (whatever is shorter) of the start of lymphodepleting chemotherapy

(palliative radiotherapy to lesions not essential for response assessment is allowed

without a minimal washout period)

- Any investigational therapy within 4 weeks or 5 half-lives (whatever is shorter) prior

to apheresis or the start of lymphodepleting chemotherapy

- History of allergic reactions to any drug or its ingredients / impurities foreseen to

be given as part of this trial according to the protocol*

- Receipt of live vaccines within 2 weeks prior to leukapheresis and start of

lymphodepleting chemotherapy

- Pregnant or breastfeeding women. Breastfeeding has to be discontinued before onset of

and during treatment and should be discontinued for at least 3 months after end of

treatment.

- Women of childbearing potential, except women who meet the following criteria:

1. post-menopausal (12 months natural amenorrhoea or 6 months amenorrhoea with serum

Follicle stimulating hormone > 40 U/ml)

2. postoperative (6 weeks after bilateral ovariectomy with or without hysterectomy)

3. regular and correct use of a contraceptive method with an Pearl Index < 1% per

year

4. sexual abstinence

5. Vasectomy of the partner

- Hypersensitivity known from medical history to one of the drugs used or their

ingredients or to drugs with a similar chemical structure

- Simultaneous participation in another interventional clinical trial (including within

the last 4 weeks before inclusion)

- Addictions or other illnesses that do not allow the person concerned to assess the

nature and extent of the clinical trial and its possible consequences

- Indications that the subject is unlikely to adhere to the protocol (e.g., lack of

compliance).

Studien-Rationale

Primary outcome:

1. Maximum tolerated dose (MTD) of MDC-CAR-BCMA001 (Time Frame - appr. 24 months):
The MTD will be defined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate.

2. Incidence and severity of adverse events and serious adverse events (Time Frame - appr. 24 months):
graded according to Common Terminology Criteria of Adverse Events V5.0

3. Incidence and severity of Cytokine release syndrome (Time Frame - appr. 24 months):
Grading of Cytokine release syndrome according to American Society for Transplantation and Cellular Therapy consensus criteria

4. Incidence and severity of Immune effector cell-associated neurotoxicity syndrome (Time Frame - appr. 24 months):
Grading of Immune effector cell-associated neurotoxicity syndrome according to American Society for Transplantation and Cellular Therapy consensus criteria

5. Incidence of dose-limiting toxicity (DLT) during DLT-evaluation period and beyond (Time Frame - appr.24 months)

Geprüfte Regime

MDC-CAR-BCMA001 (BCMA directed CAR T-cells):
Single-dose intravenous infusion of MDC-CAR-BCMA001 at the respective dose level following a conditioning chemotherapy

Quelle: ClinicalTrials.gov

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