Study of CAR T-cell Therapy in Acute Myeloid Leukemia and Multiple Myeloma

  • End date
    Jun 28, 2023
  • participants needed
  • sponsor
    AGC Biologics S.p.A.
Updated on 5 March 2021


The purpose of this first-in-man Phase I-IIa study is to evaluate the safety and antitumor activity of autologous CD44v6 CAR T-cells in patients with acute myeloid leukemia (AML) and multiple myeloma (MM).


The study is a seamless Phase I/IIa, open-label, multicenter clinical trial that combines Phase I dose escalation based on toxicity with Phase IIa dose expansion based on antitumor activity. Considering the "first in human" nature of this clinical study, the Bayesian Optimal Interval Design (BOIN) has been chosen to minimize any risks of exposure to the novel CD44v6 CAR T-cells during dose escalation. The study population is made up of patients with relapsed/refractory AML or MM expressing CD44v6.

The medicinal product under investigation (MLM-CAR44.1 T-cells) is patient specific as it is prepared starting from lymphocytes of the patient collected through lymphocyte apheresis. These autologous T-cells are expanded in vitro in large numbers and genetically modified to express the CAR CD44v6NL gene and thus acquire antitumor functions. As a safety feature, the MLM-CAR44.1 T-cells are genetically modified to also express the HSV-TK Mut2 gene (suicide gene), which can be selectively activated in case of severe toxicity through the administration of ganciclovir (GCV), leading to the death of proliferating CAR T-cells.

The aim of this study is to assess the safety, antitumor activity and feasibility of CD44v6 CAR T cell immunotherapy in AML and MM.

Condition Multiple Myeloma, Acute myeloid leukemia, Lymphoproliferative Disorder, Acute Myelogenous Leukemia (AML), Lymphoproliferative disorders, multiple myeloma (mm), acute myelogenous leukemia, anll, acute myeloblastic leukemia
Treatment MLM-CAR44.1 T-cells, cyclophosphamide and fludarabine from -5 to -3
Clinical Study IdentifierNCT04097301
SponsorAGC Biologics S.p.A.
Last Modified on5 March 2021


Yes No Not Sure

Inclusion Criteria

Patients must meet all the following inclusion criteria to be eligible for the
Written informed consent before any study-related procedure
Adults and children
Adults 18 to 75 years old with AML or MM
Children 1 to 17 years old with AML, only in Phase IIa
Confirmed diagnosis of AML or MM as follows
AML: Primary or secondary AML (any subtype except acute promyelocytic leukemia) according to World Health Organization (WHO) classification
MM with measurable disease as defined by the International Myeloma Working Group (IMWG)
Patients with relapse or refractory disease
AML patients must be unlikely to benefit from cytotoxic chemotherapy as follows
Leukemia refractory to at least 2 induction attempts
Leukemia in relapse within 1 year following complete response (CR) after at least 2 induction attempts
High-risk leukemia in adults according to 2017 European LeukemiaNet (ELN) in first relapse after a hypomethylating agent or a cycle containing cytarabine at a dose 1g/sqm a day (e.g. FLAG-IDA), except for FLT3-mutated AML
High-risk leukemia in children as defined by the Italian Association of Pediatric Hematology and Oncology (AIEOP)
Patients with MM must have a relapse or refractory disease after at least 4 different prior treatments in 3 treatment lines, or 4 treatments in 2 treatment lines in case of early relapsing patients (relapse in less than 1.5 years). Treatments include
Proteasome inhibitor
High-dose alkylating agent if patients less than 70 years old
Immunomodulatory drug (IMID)
A monoclonal antibody (i.e. anti CD38 monoclonal antibody)
Positive CD44v6 expression on tumor cells by flow cytometry
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Life expectancy of at least 12 weeks
Adequate organ function (hepatic, cardiac, pulmonary)
Recovery from toxicities of clinical consequence attributed to previous chemotherapy to CTCAE v5.0 Grade 1 (i.e., certain toxicities such as alopecia will not be considered in this category)
Ability to comply with study procedures, including hospitalization and protocol-specified acquisition of blood and/or bone marrow specimens
Willing to be followed up long term, i.e. a 15-year follow up as required by health authorities for cell and gene therapy products
Women of childbearing potential must test negative for pregnancy at enrolment and during the study

Exclusion Criteria

At screening: patients must meet none of the following exclusion criteria to
be eligible for the study
History of or candidate for allogeneic stem cell transplantation
Cardiovascular, pulmonary, renal, and hepatic functions that in the judgment of the investigator are insufficient for the patient to undergo investigational CAR T-cell therapy
Any history of or suspected current autoimmune disorders (apart from vitiligo, resolved childhood atopic dermatitis, Graves' disease clinically controlled)
History of rheumatologic disorders requiring specific treatment at any time in the patient's medical history
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Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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