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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04880564




Registration number
NCT04880564
Ethics application status
Date submitted
14/04/2021
Date registered
10/05/2021

Titles & IDs
Public title
A Study of CN1 in Combination With CN401 in Adult Patients With Relapsed/Refractory Lymphoid Malignancies
Scientific title
An Open-label, Multi-centre, Phase I/II Study to Investigate the Safety, Tolerability, and Preliminary Efficacy of CN1 in Combination With CN401 in Adult Patients With Relapsed/Refractory Lymphoid Malignancies
Secondary ID [1] 0 0
CN1-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed Lymphoid Malignancies 0 0
Refractory Lymphoid Malignancies 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CN1, 0.5mg/kg and CN401, 400mg
Treatment: Drugs - CN1, 1mg/kg and CN401, 600mg
Treatment: Drugs - CN1, 1mg/kg and CN401, 800mg
Treatment: Drugs - CN1, 3mg/kg and CN401, 800mg
Treatment: Drugs - CN1, 10mg/kg and CN401, 800mg

Experimental: A (CN1 0.5mg/kg and CN401 400mg) - Patients were administered with CN1, 0.5mg/kg, once every three week in combination with 400mg CN401 twice a day, fasted.

Dosage/Route of admin: CN1- Intravenous Infusion(IV); CN401- Tablet, Oral

Three to six patients are expected to be enrolled in each arm.

Experimental: B (CN1 1mg/kg and CN401 600mg) - Patients were administered with CN1, 1mg/kg, once every three week in combination with 600mg CN401 twice a day, fasted.

Dosage/Route of admin: CN1- Intravenous Infusion(IV); CN401- Tablet, Oral

Three to six patients are expected to be enrolled in each arm

Experimental: C (CN1 1mg/kg and CN401 800mg) - Patients were administered with CN1, 1mg/kg, once every three week in combination with 800mg CN401 twice a day, fasted.

Dosage/Route of admin: CN1- Intravenous Infusion(IV); CN401- Tablet, Oral

Three to six patients are expected to be enrolled in each arm

Experimental: D (CN1 3mg/kg and CN401 800mg) - Patients were administered with CN1, 3mg/kg, once every three week in combination with 800mg CN401 twice a day, fasted.

Dosage/Route of admin: CN1- Intravenous Infusion(IV); CN401- Tablet, Oral

Three to six patients are expected to be enrolled in each arm

Experimental: E (CN1 10mg/kg and CN401 800mg) - Patients were administered with CN1, 10mg/kg, once every three week in combination with 800mg CN401 twice a day, fasted.

Dosage/Route of admin: CN1- Intravenous Infusion(IV); CN401- Tablet, Oral

Three to six patients are expected to be enrolled in each arm


Treatment: Drugs: CN1, 0.5mg/kg and CN401, 400mg
CN1(0.5mg/kg) will be administered on Day 1 of each cycle (once every three weeks) for up to 12 months and CN401(400mg) will be administered orally twice daily.

Treatment: Drugs: CN1, 1mg/kg and CN401, 600mg
CN1(1mg/kg) will be administered on Day 1 of each cycle (once every three weeks) for up to 12 months and CN401(600mg) will be administered orally twice daily.

Treatment: Drugs: CN1, 1mg/kg and CN401, 800mg
CN1(1mg/kg) will be administered on Day 1 of each cycle (once every three weeks) for up to 12 months and CN401(800mg) will be administered orally twice daily.

Treatment: Drugs: CN1, 3mg/kg and CN401, 800mg
CN1(3mg/kg) will be administered on Day 1 of each cycle (once every three weeks) for up to 12 months and CN401(800mg) will be administered orally twice daily.

Treatment: Drugs: CN1, 10mg/kg and CN401, 800mg
CN1(10mg/kg) will be administered on Day 1 of each cycle (once every three weeks) for up to 12 months and CN401(800mg) will be administered orally twice daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To evaluate the safety and tolerability of CN1 in combination with CN401 in patients with relapsed/refractory lymphoid malignancies through Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0
Timepoint [1] 0 0
Measurements at Baseline till completion of last safety visit (270 days)
Primary outcome [2] 0 0
To determine maximum tolerated dose and/or Recommended Phase II Dose (RP2D) of CN1 in combination with CN401
Timepoint [2] 0 0
DLT assessed within 21 days after the first dose
Primary outcome [3] 0 0
To assess the change in anti-tumor activity of CN1 in combination with CN401 through Objective Response Rate analysis
Timepoint [3] 0 0
Baseline to End of the Treatment assessed up to an average of 1 year
Secondary outcome [1] 0 0
To further evaluate the safety and tolerability of CN1 in combination with CN401 in patients with relapsed/refractory lymphoid malignancies through Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0
Timepoint [1] 0 0
Measurements at Baseline till completion of last safety visit (270 days)
Secondary outcome [2] 0 0
To evaluate safety and tolerability of CN1 and CN401 in patients with relapsed/refractory lymphoid malignancies through vital signs as assessed by heart rate
Timepoint [2] 0 0
Baseline to End of the Treatment assessed up to an average of 1 year
Secondary outcome [3] 0 0
To evaluate safety and tolerability of CN1 and CN401 in patients with relapsed/refractory lymphoid malignancies through vital signs as assessed by respiratory rate
Timepoint [3] 0 0
Baseline to End of the Treatment assessed up to an average of 1 year
Secondary outcome [4] 0 0
To evaluate safety and tolerability of CN1 and CN401 in patients with relapsed/refractory lymphoid malignancies through vital signs as assessed by body temperature
Timepoint [4] 0 0
Baseline to End of the Treatment assessed up to an average of 1 year
Secondary outcome [5] 0 0
To evaluate safety and tolerability of CN1 and CN401 in patients with relapsed/refractory lymphoid malignancies through vital signs as assessed by pulse, systolic blood pressure, and diastolic blood pressure
Timepoint [5] 0 0
Baseline to End of the Treatment assessed up to an average of 1 year
Secondary outcome [6] 0 0
To characterize the pharmacokinetics of CN1 and CN401 when administered in combination through Area under the under the drug concentration-time curve.
Timepoint [6] 0 0
Baseline to End of the Treatment assessed up to an average of 1 year
Secondary outcome [7] 0 0
To characterize the pharmacokinetics of CN1 and CN401 when administered in combination through Cmax and Tmax.
Timepoint [7] 0 0
Baseline to End of the Treatment assessed up to an average of 1 year
Secondary outcome [8] 0 0
To characterize the pharmacokinetics of CN1 and CN401 when administered in combination through Apparent terminal half-life (t½).
Timepoint [8] 0 0
Baseline to End of the Treatment assessed up to an average of 1 year
Secondary outcome [9] 0 0
To characterize the pharmacokinetics of CN1 and CN401 when administered in combination through Apparent terminal elimination rate constant (Kel).
Timepoint [9] 0 0
Baseline to End of the Treatment assessed up to an average of 1 year
Secondary outcome [10] 0 0
To characterize the pharmacokinetics of CN1 and CN401 when administered in combination through Apparent clearance.
Timepoint [10] 0 0
Baseline to End of the Treatment assessed up to an average of 1 year
Secondary outcome [11] 0 0
To characterize the pharmacokinetics of CN1 and CN401 when administered in combination through Accumulation ration.
Timepoint [11] 0 0
Baseline to End of the Treatment assessed up to an average of 1 year
Secondary outcome [12] 0 0
To characterize the pharmacokinetics of CN1 and CN401 when administered in combination through Apparent terminal volume of distribution.
Timepoint [12] 0 0
Baseline to End of the Treatment assessed up to an average of 1 year
Secondary outcome [13] 0 0
To further assess change in anti-tumor activity of CN1 in combination with CN401 through ORR
Timepoint [13] 0 0
Baseline to End of the treatment visit assessed up to an average of 1 year

Eligibility
Key inclusion criteria
1. Age = 18 years on the day of signing informed consent.
2. Based on pathology review at the local institution, using the most recent edition of the World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues as guidance, leading to the diagnosis of one of the following diseases and their histological subtypes: PTCL, CTCL, and B-cell NHL.
3. Patients must have relapsed or refractory disease after at least one prior systemic anti-tumor treatment.
4. The patients enrolled in Phase II of the study should have received NOT more than five lines of prior systemic therapies.
5. Patients must have at least one evaluable lesion per Lugano 2014 Criteria. Measurable lesions are defined as those that can be accurately measured in at least two dimensions with conventional techniques (positron emission tomography/Computed tomography [PET/CT], magnetic resonance imaging [MRI]) or as > 1.5 cm with spiral CT scan. Patients with non-measurable lesions but assessable diseases (e.g., marrow disease without other radiographically measurable diseases) may be enrolled on a case-by-case basis in discussion with the Sponsor.
6. ECOG performance status 0 to 2.
7. At least 3 months of expected survival.
8. Adequate organ functions, further defined as:

* Hemoglobin = 9 g/dL.
* Absolute neutrophil count (ANC) = 1 × 10E+09/L.
* Platelets = 50 × 10E+09/L (patient without bone marrow [BM] involvement) and = 30 × 10E+09/L (patient with BM involvement).
* Total bilirubin = 1.5 times the upper limit of normal (ULN).
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN if known liver involvement. The ALT and AST should be = 1.5 × ULN in absence of liver involvement/metastasis.
* Serum creatinine = 2.0 mg/dL or calculated creatinine clearance = 50 mL/min (as calculated by the Cockcroft-Gault method).
* Activated partial thromboplastin time (APTT) or international normalized ratio (INR) = 1.5 × ULN (unless patient is receiving anticoagulants).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Received any anti-tumour treatment (i.e., chemotherapy, radiotherapy, immunotherapy, biologic therapy, endocrine therapy, etc.,) within four weeks (or five half-lives of the agent, whichever is shorter) prior to the first dose of study drugs, with the following exceptions:

1. Palliative radiation therapy within 2 weeks.
2. Oral small molecule targeted therapies within 2 weeks prior to the first dose of study drugs or within 5 half-lives of the drug, whichever is shorter.
3. Herbal medications within 7 days prior to the first dose.
2. Received other investigational agents (not yet approved by any regulatory agency) within four weeks prior to the first dose of any study drugs.
3. Immunosuppressive medication > 10 mg prednisolone per day or equivalent within 14 days prior to the first dose of the study drug. Note: Use of immunosuppressive medications as prophylaxis in subjects with contrast allergies are acceptable. In addition, temporary uses of corticosteroids considered non-clinically significant may be approved on a case-by-case basis in discussion with the Sponsor.
4. Known clinically active central nervous system (CNS) or meningeal involvement. In the absence of symptoms, investigation into CNS involvement is not required. Patients are eligible if metastases have been treated, patients are neurologically returned to baseline or neurologically stable for at least four weeks and not requiring steroid therapy for at least one week prior to Cycle 1 Day 1.
5. Active infection and in current need of, or likely to need, intravenous (IV) anti-infective therapy.
6. History of immunodeficiency, including history of any positive test result for human immunodeficiency virus (HIV) antibody.
7. Patients who are known to be hepatitis B or C positive (positive HBsAg and/or detectable level of HBV DNA or positive HCV antibody).
8. Active Epstein Barr virus (EBV) unrelated to underlying lymphoma (positive serology for anti-EBV VCA IgM antibody and negative for anti-EBV EBNA IgG antibody, or clinical manifestations and positive EBV polymerase chain reaction [PCR] consistent with active EBV infection).
9. Active CMV (positive serology for anti-CMV IgM antibody, negative for anti-CMV IgG antibody, and positive CMV PCR with clinical manifestations consistent with active CMV infection) and requiring therapy.
10. Current history of a serious uncontrolled medical disorder, metabolic dysfunction, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or render the patient at high risk from treatment complications.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/09/2022
Sample size
Target
Accrual to date
Final
7
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash Health - Monash Medical Centre - Bentleigh
Recruitment postcode(s) [1] 0 0
3168 - Bentleigh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Curon Biopharmaceutical (Australia) Co Pty Ltd
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jake Shortt
Address 0 0
Monash Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04880564