Trial Title:
Dose-escalating Trial With Allo-RevCAR01-T Cells in Combination With CD123 Target Module (R-TM123) for Participants With Selected Hematologic Malignancies Positive for CD123
NCT ID:
NCT05949125
Condition:
Acute Myeloid Leukemia, in Relapse
Acute Myeloid Leukemia Refractory
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Hematologic Neoplasms
Cyclophosphamide
Fludarabine
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
Dose escalation follows a BOIN comb design with 3 dose levels of 100, 250, and 500
million Allo-RevCAR01-T and 3 dose levels of R-TM123 resulting in a maximum of 9 dose
levels.
Given 1 participant dose level cohorts, there will be an inherent stagger between each
participant equivalent to the DLT window of 28 days
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
Cyclophosphamide (Non-IMP, Lymphodepletion)
Description:
Intravenous infusion over 3 days (d-5 to d-3)
Arm group label:
Allo-RevCAR01-T-CD123 treatment
Intervention type:
Other
Intervention name:
Fludarabine (Non-IMP, Lymphodepletion)
Description:
Intravenous infusion over 3 days (d-5 to d-3)
Arm group label:
Allo-RevCAR01-T-CD123 treatment
Intervention type:
Drug
Intervention name:
R-TM123
Description:
Intravenous infusion over 20 days
Arm group label:
Allo-RevCAR01-T-CD123 treatment
Other name:
R-TM123 is one component of the Allo-RevCAR01-T-CD123 treatment
Intervention type:
Drug
Intervention name:
Allo-RevCAR01-T
Description:
A single dose of Allo-RevCAR01-T will be administered as IV infusion on Treatment day 1.
Allo-RevCAR01-T will not be administered again within this study.
Arm group label:
Allo-RevCAR01-T-CD123 treatment
Other name:
Allo-RevCAR01-T is one component of the Allo-RevCAR01-T-CD123 treatment
Summary:
The Allo-RevCAR01-T-CD123 drug is a combination of a cellular component (Allo-RevCAR01-T)
with a recombinant antibody derivative (R-TM123), which together form the active drug.
The cellular component Allo-RevCAR01-T consists of an allogeneic human T-cell genetically
multi-edited and expressing a reversed, universal chimeric antigen receptor (RevCAR)
presenting an extracellular peptide epitope (RevCAR epitope). R TM123 functions as a
bridging module between Allo RevCAR01-T and a CD123-expressing target cancer cell by
selectively binding the RevCAR epitope and CD123.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female participants, age ≥18 years.
2. HLA type of participant must match at HLA B and C loci
3. Participants with CD123+ AML (defined as ≥20% of leukemic cells expressing CD123 at
any point in the course of disease)
- Participants with MRD+ AML are eligible but must meet specific criteria i. MRD
positivity must be based on assays and markers supported by consensus
guidelines [Heuser2021] and in the judgment of the investigator must confer
negative prognostic risk highly likely to result in relapse.
ii. Must have received or be ineligible for allogeneic stem cell transplant. iii.
Must be approved by the Sponsor for inclusion in the study.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Life expectancy of at least 3 months in the judgment of the investigator.
6. Adequate renal and hepatic laboratory assessments:
7. Adequate cardiac function
8. Permanent venous access existing (e.g., port-system) or willing to have such a
device inserted.
9. Able to give written informed consent.
10. Weight ≥45 kg.
11. Negative pregnancy; routinely using a highly effective method of birth control
Exclusion Criteria:
1. Acute promyelocytic leukemia (t15;17).
2. AML with only extramedullary manifestations (e.g., chloroma, primary myeloid
sarcoma)
3. Acute manifestationof AML in the central nervous system.
4. Bone marrow failure syndromes
5. Cardiac disease: heart failure (New York Heart Association III or IV); unstable
coronary artery disease, myocardial infarction, or serious cardiac ventricular
arrhythmias requiring anti-arrhythmic therapy within the last 6 months prior to
study entry.
6. Active pulmonary disease with clinically relevant hypoxia
7. Parkinson's disease or epilepsy with clinical symptoms in the previous 12 months .
8. Stroke, seizure, or intracranial hemorrhage in the past 12 months.
9. History or presence of disseminated intravascular coagulation (DIC), deep vein
thrombosis or thromboembolism within 3 months prior to start of treatment.
10. Active infectious disease considered by investigator to be incompatible with
protocol or being contraindications for lymphodepletion therapy
11. Toxicity from prior anticancer treatment has not resolved to Grade ≤1 or baseline.
12. Allogeneic stem cell transplantation within last 2 months or GvHD requiring
immunosuppressive therapy.
13. Vaccination with live viruses <2 weeks prior to lymphodepletion therapy.
14. Major surgery within 28 days prior to start of R-TM123 infusion.
15. Prior malignancy in the past 3 years or any malignancy requiring ongoing active
therapy other than adjuvant endocrine therapy. Participants with resected or ablated
tumors, such as basal cell carcinoma of skin, carcinoma-in-situ of the cervix, or
other tumors considered cured by local treatment may be considered for the study
with Sponsor approval.
16. Treatment with any investigational drug substance or experimental therapy within 4
weeks or 5 half-lives (whichever is shorter) of the substance prior to
lymphodepletion.
17. Treatment with anti-leukemic therapy within 4 weeks or 5 half-lives (whichever is
shorter) prior to lymphodepletion.
18. Prior treatment with gene modified cell products.
19. Use of checkpoint inhibitors within 5 half-lives of the specific drug.
20. Autoimmune diseases requiring systemic steroids or other systemic
immunosuppressants.
21. Pregnant or breastfeeding women.
22. Psychologic disorders with treatment modifications required within the last 3
months, drug and/or significant active alcohol abuse as per investigator's medical
judgement. Depression or anxiety due to presence of the underlying malignancy may be
exempted with Sponsor approval.
23. History of human immunodeficiency virus (HIV) or human T-lymphotropic virus (HTLV)
or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).
24. Presence of autoantibodies against lupus La protein (La)/ Sjögren syndrome type B
antigen (SS-B) or presence or history of autoimmune diseases associated with such
antibodies
25. Known hypersensitivity to cellular component (Allo-RevCAR01-T) and/or TM (R-TM123)
excipients or to compounds of the lymphodepletion therapy, tocilizumab, or
corticosteroids.
26. Evidence that the participant is not likely or able to follow the study protocol
(e.g., lacking compliance) in the judgment of the investigator.
27. Participant unable to understand the informed consent and possible consequences of
the participation in the clinical trial in the judgement of the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Universitätsklinikum Ulm
Address:
City:
Ulm
Zip:
89081
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Elisa Sala, MD
Email:
elisa.sala@uniklinik-ulm.de
Facility:
Name:
Klinikum der Universität München
Address:
City:
Munich
Zip:
81377
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Marion Subklewe, Prof.
Email:
Marion.Subklewe@med.uni-muenchen.de
Facility:
Name:
Universitätsklinikum Würzburg
Address:
City:
Würzburg
Zip:
97080
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Chatterjee Manik, MD
Email:
Chatterjee_m@ukw.de
Facility:
Name:
Universitätsklinikum Marburg
Address:
City:
Marburg
Zip:
35032
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Stephan Metzelder, Prof.
Email:
metzelde@med.uni-marburg.de
Facility:
Name:
Universitätsklinikum Dresden
Address:
City:
Dresden
Zip:
01307
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Martin Wermke, Prof.
Email:
martin.wermke@ukdd.de
Facility:
Name:
Charité Universitätsmedizin Berlin
Address:
City:
Berlin
Zip:
13353
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Jörg Westermann, Prof.
Email:
joerg.westermann@charite.de
Facility:
Name:
Medizinische Hochschule Hannover
Address:
City:
Hannover
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Felizitas Thol, Prof.
Email:
Thol.Felicitas@mh-hannover.de
Facility:
Name:
Universitätsklinikum Köln
Address:
City:
Köln
Zip:
50937
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Lukas Frenzel, PD
Email:
lukas.frenzel@uk-koeln.de
Facility:
Name:
Erasmus University Medical Center
Address:
City:
Rotterdam
Zip:
3015
Country:
Netherlands
Status:
Not yet recruiting
Contact:
Last name:
Mojca Jongen-Lavrencic, Dr.
Email:
m.lavrencic@erasmusmc.nl
Facility:
Name:
Amsterdam University Medical Center
Address:
City:
Amsterdam
Zip:
1081
Country:
Netherlands
Status:
Not yet recruiting
Contact:
Last name:
Arjan van de Loosdrecht, Prof.
Email:
a.vandeloosdrecht@amsterdamumc.nl
Facility:
Name:
University Medical Center Groningen (UMCG)
Address:
City:
Groningen
Zip:
9700
Country:
Netherlands
Status:
Not yet recruiting
Contact:
Last name:
Gerwin Huls, Prof.
Email:
g.huls@umcg.nl
Start date:
January 3, 2024
Completion date:
June 2026
Lead sponsor:
Agency:
AvenCell Europe GmbH
Agency class:
Industry
Collaborator:
Agency:
Allucent (NL) BV
Agency class:
Other
Source:
AvenCell Europe GmbH
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05949125
