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Dose-escalating Trial With UniCAR02-T Cells and CD123 Target Module (TM123) in Patients With Hematologic and Lymphatic Malignancies

NCT04230265

Description:

This dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug UniCAR02-T-CD123 in patients with hematologic and lymphatic malignancies positive for CD123 marker. The UniCAR02-T-CD123 drug is a combination of a cellular component (UniCAR02-T) with a recombinant antibody derivative (TM123) which together forms the active drug.

Related Conditions:
  • Acute Myeloid Leukemia
  • B-Cell Acute Lymphoblastic Leukemia
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dose-escalating Trial With UniCAR02-T Cells and CD123 Target Module (TM123) in Patients With Hematologic and Lymphatic Malignancies
  • Official Title: Multicenter, Open-label, Adaptive Design Phase I Trial With Genetically Modified T-cells Carrying Universal Chimeric Antigen Receptors (UniCAR02-T) in Combination With CD123 Target Module (TM123) for the Treatment of Patients With Hematologic and Lymphatic Malignancies Positive for CD123

Clinical Trial IDs

  • ORG STUDY ID: UC02-123-01
  • SECONDARY ID: 2019-001339-30
  • NCT ID: NCT04230265

Conditions

  • Acute Myeloid Leukemia (AML)
  • B-cell Acute Lymphoblastic Leukemia (b-ALL)
  • Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Interventions

DrugSynonymsArms
Cyclophosphamide (Non-IMP)UniCAR02-T-CD123
Fludarabine (Non-IMP)UniCAR02-T-CD123
TM123 (IMP)UniCAR02-T-CD123
UniCAR02-T (IMP)UniCAR02-T-CD123

Purpose

This dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug UniCAR02-T-CD123 in patients with hematologic and lymphatic malignancies positive for CD123 marker. The UniCAR02-T-CD123 drug is a combination of a cellular component (UniCAR02-T) with a recombinant antibody derivative (TM123) which together forms the active drug.

Trial Arms

NameTypeDescriptionInterventions
UniCAR02-T-CD123ExperimentalPreconditioning (lymphodepletion) with cyclophosphamide and fludarabine, followed by combination treatment of genetically modified T-cells carrying universal chimeric antigen receptors (UniCAR02-T) with the recombinant antibody derivative TM123.
  • Cyclophosphamide (Non-IMP)
  • Fludarabine (Non-IMP)
  • TM123 (IMP)
  • UniCAR02-T (IMP)

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female patients, age ≥ 18 years

          2. Documented definitive diagnosis of CD123 positive of at least 20 % positive blasts in
             AML, B-ALL or BPDCN (according to standard of care testing) that is

               -  Relapsed or refractory AML,

               -  Relapsed or refractory B-ALL (in patients aged over 25 years or over 18 years
                  without access to an approved chimeric antigen receptor (CAR)-T cell product at
                  time point of potential inclusion into this study),

               -  Patients with histological and/or cytological evidence of BPDCN in the peripheral
                  blood, bone marrow, spleen, lymph nodes, skin, and/or other sites that is
                  persistent/recurrent following prior standard of care treatment for BPDCN

          3. Eastern Cooperative Oncology Group (ECOG) of 0 to 1

          4. Life expectancy of at least 2 months

          5. Adequate renal and hepatic laboratory assessments:

          6. Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF) of ≥ 45 % as
             assessed by transthoracic two-dimensional echocardiography

          7. Permanent venous access existing (e.g. port-system) resp. acceptance of implantation
             of a device

          8. Able to give written informed consent

          9. Weight ≥ 45 kg

         10. Negative pregnancy; routinely using a highly effective method of birth control

        Exclusion Criteria:

          1. Acute promyelocytic leukemia (t15;17) and T-ALL

          2. Manifestation of AML, ALL or BPDCN in central nervous system

          3. Bone marrow failure syndromes

          4. Cardiac disease: i.e. heart failure (NYHA 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

          5. Patients undergoing renal dialysis

          6. Pulmonary disease with clinical relevant hypoxia

          7. Parkinson, epilepsy and, stroke or presence or history of seizures, paresis, aphasia,
             central nervous system (CNS) or intracranial hemorrhage

          8. History or presence of disseminated intravascular coagulation (DIC) or thromboembolism

          9. Hemolytic anemia

         10. Multiple sclerosis

         11. Active infectious disease considered by investigator to be incompatible with protocol
             or being contraindications for lymphodepletion therapy

         12. Presence of urotoxicity from previous chemo- or radiotherapy or urinary outflow
             obstruction

         13. Allogeneic stem cell transplantation within last two months or Graft versus host
             disease (GvHD) requiring immunosuppressive therapy

         14. Vaccination with live viruses less than 2 weeks prior lymphodepletion therapy

         15. Major surgery within 28 days

         16. Other malignancy requiring active therapy but adjuvant endocrine therapy is allowed

         17. Treatment with any investigational drug substance or experimental therapy within 4
             weeks or 5 half-lives (whatever is shorter) of the substance prior to the day of
             apheresis

         18. Prior treatment with gene therapy products

         19. Use of checkpoint inhibitors within 5 half-lives of the respective substance

         20. Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants

         21. Pregnant or breastfeeding women

         22. Psychologic disorders, drug and/or significant active alcohol abuse

         23. Known history of human immunodeficiency virus (HIV) or active/chronic infection with
             hepatitis C virus (HCV) or hepatitis B virus (HBV)

         24. Presence of autoantibodies against La/Sjögren syndrome (SS)-B or presence or history
             of autoimmune diseases

         25. Known hypersensitivity to cellular component (UniCAR02-T) and/or targeting module
             (TM123) excipients or to compounds of the lymphodepletion therapy or tocilizumab or
             corticosteroids

         26. Evidence suggesting that the patient is not likely to follow the study protocol

         27. Incapability of understanding purpose and possible consequences of the trial

         28. Patients who should not be included according to the opinion of the investigator
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability
Time Frame:DLT period (infusion period of TM123 + 7 days or + 28 days in patients with complete blast clearance) until Safety Follow-up 1 (infusion period of TM123 + 28 days + 3 months)
Safety Issue:
Description:Incidence and intensity of adverse events graded according to CTCAE V5.0

Secondary Outcome Measures

Measure:Recommended phase 2 dose (RP2D)
Time Frame:DLT period (infusion period of TM123 + 7 days or + 28 days in patients with complete blast clearance)
Safety Issue:
Description:The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.
Measure:Complete remission (CR), incomplete remission (CRi) and partial remission (PR)
Time Frame:until fifteen years after last UniCAR02-T administration
Safety Issue:
Description:CR: Bone marrow blasts < 5%, absence of extramedullary disease, absolute neutrophil count > 1 Gpt/L and platelet count > 100 Gpt/L. Level of MRD should be measured in patients achieving CR in case as suitable marker exists. CRi: All criteria for CR except residual thrombocytopenia (platelets < 100 Gpt/L) and/or neutropenia (absolute neutrophil count < 1 Gpt/L). PR: All hematological criteria for CR with bone marrow blasts 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50 %.
Measure:Disease stabilization (DS)
Time Frame:until fifteen years after last UniCAR02-T administration
Safety Issue:
Description:Reduction of blast percentage by 25% compared to baseline without normalization of peripheral blood counts to levels not qualifying for PR or CR.
Measure:Best response rate
Time Frame:until fifteen years after last UniCAR02-T administration
Safety Issue:
Description:The best observed response during observational period. Response states are ordered descending as follows: CR > CRi > PR > DS > refractory disease.
Measure:Progression free survival (PFS)
Time Frame:until fifteen years after last UniCAR02-T administration
Safety Issue:
Description:The time from first treatment with TM123 and UniCAR02-T until disease progression or death. If no progress of death was observed during the observational period, the patient's progression free survival time will be censored on the date the patient was last seen progression-free and alive.
Measure:Overall survival (OS)
Time Frame:until fifteen years after last UniCAR02-T administration
Safety Issue:
Description:The number of days between the first study drug administration and death from any cause. If death was not observed during the observational period, the patient's overall survival time will be censored on the date the patient was last seen alive.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Cellex Patient Treatment GmbH

Last Updated

May 26, 2020