Trial Title:
An Adaptive Open-label Multicentre Phase 1/2 Trial, to Determine the Recommended Phase 2 Dose of CCTx-001, and to Assess Safety, Tolerability, and Clinical Activity in Patients With Relapsed/Refractory Acute Myeloid Leukaemia
NCT ID:
NCT06281847
Condition:
Acute Myeloid Leukemia, in Relapse
Acute Myeloid Leukemia Refractory
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Conditions: Keywords:
Acute Myeloid Leukemia
Relapsed
Refractory
Open-label
Safety
Tolerability
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
The study comprises 4 periods:
- The pre-treatment period will consist of screening for eligibility, leukapheresis
and a pre-treatment evaluation (prior to Lymphodepleting Chemotherapy (LDC)).
- The treatment period will start with LDC, followed by CCTx-001 infusion 2 to 7 days
after completion of LDC. A first response evaluation will be performed at
approximately 28 days after CCTx-001 infusion.
- The post-treatment period will consist of further clinical activity and safety
follow-up visits at regular timepoints after CCTx-001 infusion, starting after the
Month 3 visit up to the Month 24 visit.
- The long-term follow-up period will start after the Month 24 visit up to 15 years
post CCTx-001 infusion.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Genetic
Intervention name:
CCTx-001
Description:
Frozen CAR T-cells suspensions in media containing dimethyl sulfoxide (DMSO)
Arm group label:
Open Label CCTx-001 infusion
Summary:
The purpose of this adaptive Phase 1/2 study is to evaluate the safety, tolerability,
pharmacokinetics (PK), and antileukemic activity of CCTx-001 in adult patients with r/r
Acute Myeloid Leukemia (AML). CCTx-001 targets IL-1RAP, which is specifically expressed
in leukemic cells. In preclinical studies, IL-1RAP-targeted Chimeric antigen receptors
(CARs) have demonstrated encouraging activity in both in vitro and in vivo experiments in
AML models. Based on these promising preclinical results, it is expected that CCTx-001
could potentially alter the natural course of r/r AML and provide a potential novel
treatment option.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients with active (> 5 % blasts in bone marrow) r/r AML (WHO 2022) who have
exhausted their therapeutic alternatives or have contraindications to these
alternatives as judged by the treating physician defined as either:
a. Primary refractory: i. Patients who failed after two cycles of intensive
induction including high-dose and/or standard dose cytarabine (including liposomal
formulation), +/- anthracycline, +/- antimetabolite, +/- targeted therapy or ii.
Older patients or patients unfit to receive intensive induction courses who failed
after two cycles of venetoclax + azacitidine or 4 cycles of azacitidine b.
Relapsing: i. Patients with early relapse after CR to first line therapy (within ≤ 6
months after CR1) or ii. Patients with relapse after later lines of therapy (Relapse
after CR≥2) c. Patients relapsing after allogeneic hematopoietic stem cell
transplant: i. Patients must be at least 3 months from hematopoietic stem cell
transplant (HSCT) at the time of consent, and ii. Off immunosuppression for at least
1 month at the time of consent, and iii. Have no active graft versus host disease
(GvHD)
2. Have a circulating blast count of less than 20,000/mm3 (control with hydroxyurea is
allowed)
3. Absolute Lymphocyte count of >200/mm3
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
5. Life expectancy of more than 3 months
6. Patient is ≥ 18 years of age at the time of informed consent
7. Read, understood, and signed the informed consent form (ICF) prior to any study
procedures
8. Patient is willing and able to adhere to the study visit schedule and other protocol
requirements
9. Eligible for leukapheresis
10. Treatment-related toxicities of previous therapies have completely resolved
11. Adequate organ function as confirmed by clinical laboratory values, defined as:
1. Adequate bone marrow function to receive LDC as assessed by the Investigator
2. Serum creatinine [< 1.5 x the upper limit of normal (ULN) or creatinine
clearance (CrCl) > 45 mL/min] (estimated by Cockcroft Gault or Modification of
Diet in Renal Disease (MDRD); see Appendix 14.3 for calculation)
3. Alanine aminotransferase [≤ 3 x ULN and total bilirubin < 1.5 mg/dL (or < 3.0
mg/dL] for patients with Gilbert's syndrome or leukemic infiltration of the
liver)]
4. Adequate pulmonary function, defined as [≤ Grade 1 dyspnoea according to CTCAE
and oxygen saturation (SaO2) ≥ 92% on room air and forced expiratory volume in
the first second ≥ 50%]
5. Ejection fraction > 40% assessed by an echocardiogram (ECHO) or multigated
acquisition (MUGA) scan performed within 1 month before CCTx-001 infusion
12. Women of childbearing potential* (WOCBP) must have a negative serum pregnancy test
performed at screening and within 7 days before enrolment
13. WOCBP or males whose sexual partners are WOCBP must be able and willing to use at
least 1 highly effective method of contraception during the study and for 12 months
after the last dose of LDC. For the definition and list of highly effective methods
of contraception.
Exclusion Criteria:
1. Patients with an acute promyelocytic leukaemia: t(15;17)(q22;q12); (promyelocytic
leukaemia/retinoic acid receptor alpha) and variants
2. Patients with active central nervous system (CNS) leukaemia involvement. If the
patient has prior history of CNS leukaemia, they must have a negative cerebrospinal
fluid (CSF) assessment and magnetic resonance imaging (MRI) or computed tomography
(if MRI is not feasible) of the brain demonstrating no evidence of CNS disease
3. Patients with isolated extramedullary AML disease
4. Patients who received previous treatment targeting IL-1RAP or previous gene therapy
5. Patients who underwent allo-HSCT within 90 days prior to leukapheresis
6. Patients who received donor lymphocyte infusion within 60 days prior to
leukapheresis
7. Patients with active GvHD
8. Patients with history of another primary malignancy other than disease under study
unless the patient has been free of the disease for ≥ 2 years, except for the
following non-invasive malignancies:
1. Basal cell carcinoma of the skin
2. Squamous cell carcinoma of the skin
3. Carcinoma in situ of the cervix
4. Carcinoma in situ of the breast
5. Incidental histologic finding of prostate cancer (T1a or T1b) or prostate
cancer that is curative
6. Other completely resected stage 1 solid tumour with low risk for recurrence
9. Presence of systemic fungal, bacterial, viral, or other infection (including
tuberculosis) that is uncontrolled despite appropriate antibiotics or other
treatments
10. Active or prior history of hepatitis B or hepatitis C infection
11. History of or active human immunodeficiency virus (HIV) infection
12. Active macrophage activation syndrome (MAS) as evidenced by laboratory abnormalities
(e.g.: elevated ferritin, elevated triglycerides, haemophagocytosis on the bone
marrow sample) and/or clinical signs
13. History or presence of an active and clinically relevant CNS disorder such as
epilepsy, generalised seizure disorder, paresis, aphasia, stroke, cerebral oedema,
severe brain injury, dementia, multiple sclerosis, Parkinson's disease, cerebellar
disease, organic brain syndrome, or posterior reversible encephalopathy syndrome, or
any autoimmune disease with CNS involvement
14. Patients with active autoimmune disorders or active neurological or inflammatory
disorders (e.g., Guillain-Barre Syndrome, Amyotrophic Lateral Sclerosis) requiring
immunosuppressive therapy or corticosteroid therapy (defined as >20 mg/day
prednisone or equivalent). Physiologic replacement, topical, and inhaled steroids
are permitted.
15. Use of the following (see Section 8.3 for full details):
1. Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or
equivalent) within 7 days prior to leukapheresis or 72 hours prior to CCTx-001
infusion. Physiologic replacement, topical, and inhaled steroids are permitted.
2. Immunosuppressive therapies within 4 weeks prior to signing the ICF (e.g.,
calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate,
rapamycin, thalidomide, immunosuppressive antibodies such as anti-tumour
necrosis factor [TNF], anti-IL-6, or anti-IL-6 receptor [IL-6R])
3. Cytotoxic chemotherapeutic agents (including intrathecal) within 14 days prior
to leukapheresis.
4. Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with
fludarabine or cladribine within 3 months of leukapheresis
5. Experimental agents within 4 weeks prior to signing the ICF unless no response
or progressive disease (PD) is documented on the experimental therapy and at
least 3 half-lives have elapsed prior to signing the ICF.
6. Therapeutic anticoagulation
16. History of any one of the following cardiovascular conditions within the past 6
months prior to signing the ICF:
1. Class III or IV heart failure as defined by the New York Heart Association
2. Cardiac angioplasty or stenting
3. Myocardial infarction
4. Unstable angina
5. Other clinically significant cardiac disease
17. Known hypersensitivity to DMSO or other excipients
18. Uncontrolled medical, psychological, familial, sociological, or geographical
conditions that do not permit compliance with the protocol, as judged by the
Investigator; or unwillingness or inability to follow the procedures required in the
protocol.
19. Abnormal findings and/or clinically significant Grade ≥3 non-haematological toxicity
and any other medical condition(s) or laboratory findings that, in the opinion of
the Investigator, might jeopardise the patient's safety.
20. Presence of any condition that confounds the ability to interpret data from the
study based on Investigator´s judgement.
21. Any planned medical/surgical treatment that might interfere with the ability to
comply with the study requirements.
22. Pregnant or nursing women. NOTE: WOCBP must have a negative serum pregnancy test
performed within 48 hours of starting LDC
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Besançon Regional and University Hospital
Address:
City:
Besançon Cedex
Country:
France
Contact:
Last name:
Eric Deconinck
Investigator:
Last name:
Eric Deconinck
Email:
Principal Investigator
Facility:
Name:
Hospital Saint Louis
Address:
City:
Paris
Country:
France
Contact:
Last name:
Nicolas Boissel
Investigator:
Last name:
Nicolas Boissel
Email:
Principal Investigator
Facility:
Name:
Ludwig-Maximilians University of Munich
Address:
City:
Munich
Country:
Germany
Contact:
Last name:
Marion Subklewe
Investigator:
Last name:
Marion Subklewe
Email:
Principal Investigator
Facility:
Name:
University Hospital Ulm
Address:
City:
Ulm
Country:
Germany
Contact:
Last name:
Elisa Sala
Investigator:
Last name:
Elisa Sala
Email:
Principal Investigator
Facility:
Name:
Vall d'Hebron University Hospital
Address:
City:
Barcelona
Country:
Spain
Contact:
Last name:
Pere Barba
Investigator:
Last name:
Pere Barba
Email:
Principal Investigator
Facility:
Name:
Karolinska University Hospital
Address:
City:
Stockholm
Country:
Sweden
Contact:
Last name:
Stephan Mielke
Investigator:
Last name:
Stephan Mielke
Email:
Principal Investigator
Start date:
February 2024
Completion date:
August 2041
Lead sponsor:
Agency:
Advesya SAS
Agency class:
Industry
Source:
Advesya SAS
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06281847
