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).
