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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06248086




Registration number
NCT06248086
Ethics application status
Date submitted
31/01/2024
Date registered
8/02/2024

Titles & IDs
Public title
A Study to Find a Suitable Dose of ASP2802 in People With CD20-positive B-cell Lymphomas
Scientific title
A First-in-Human, Phase 1 Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of a Single-Induction Dose of convertibleCARTM-T Cells Armed With MicAbodyTM Protein (ASP2802) Followed by Maintenance Booster Doses of the MicAbody Protein in Patients With CD20-Positive Relapsed or Refractory B-Cell Lymphomas
Secondary ID [1] 0 0
2802-CL-0101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ASP2802
Treatment: Drugs - MA-20

Experimental: Group A: ASP2802 Low Dose followed by MA-20 - Participants will receive a low dose of ASP2802 on Day 0 of cycle 1. Each participant will then receive up to 2 doses of MA-20 booster in each 28-day cycle.

Experimental: Group B: ASP2802 Intermediate Dose followed by MA-20 - Participants will receive an intermediate dose of ASP2802 on Day 0 of cycle 1. Each participant will then receive up to 2 doses of MA-20 booster in each 28-day cycle, with dose level(s) selected from Group A.

Experimental: Group C: ASP2802 High Dose followed by MA-20 - Participants will receive a higher dose of ASP2802 on Day 0 of cycle 1. Each participant will then receive up to 2 doses of MA-20 booster in each 28-day cycle, with dose level(s) selected from Group B.


Treatment: Drugs: ASP2802
Intravenous (IV) infusion

Treatment: Drugs: MA-20
IV infusion

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Up to 10 months
Primary outcome [2] 0 0
Number of participants with Adverse Events (AEs)
Timepoint [2] 0 0
Up to 26 months
Primary outcome [3] 0 0
Number of participants with Serious Adverse Events (SAEs)
Timepoint [3] 0 0
Up to 26 months
Primary outcome [4] 0 0
Number of participants with laboratory value abnormalities and/or AEs
Timepoint [4] 0 0
Up to 26 months
Primary outcome [5] 0 0
Number of Participants with vital sign abnormalities and/or AEs
Timepoint [5] 0 0
Up to 26 months
Primary outcome [6] 0 0
Number of Participants with electrocardiogram (ECG) abnormalities and/or AEs
Timepoint [6] 0 0
Up to 26 months
Primary outcome [7] 0 0
Number of Participants at each grade of Eastern Cooperative Oncology Group (ECOG) performance status scores
Timepoint [7] 0 0
Up to 26 months
Secondary outcome [1] 0 0
Pharmacokinetics (PK) of ASP2802 in blood: Maximum Concentration (Cmax)
Timepoint [1] 0 0
Up to 26 months
Secondary outcome [2] 0 0
PK of ASP2802 in blood: Time to maximum concentration (tmax)
Timepoint [2] 0 0
Up to 26 months
Secondary outcome [3] 0 0
PK of ASP2802 in blood: Area under the concentration-time curve (AUC)0-28d
Timepoint [3] 0 0
Up to 26 months
Secondary outcome [4] 0 0
PK of ASP2802 in blood: concentration
Timepoint [4] 0 0
Up to 26 months
Secondary outcome [5] 0 0
PK of MA-20 in serum: Cmax
Timepoint [5] 0 0
Up to 26 months
Secondary outcome [6] 0 0
PK of MA-20 in serum: tmax
Timepoint [6] 0 0
Up to 26 months
Secondary outcome [7] 0 0
PK of MA-20 in serum: Trough concentration (Ctrough)
Timepoint [7] 0 0
Up to 26 months
Secondary outcome [8] 0 0
PK of MA-20 in serum: AUC0-14d
Timepoint [8] 0 0
Up to 26 months
Secondary outcome [9] 0 0
PK of MA-20 in serum: Apparent terminal half-life (t1/2)
Timepoint [9] 0 0
Up to 26 months
Secondary outcome [10] 0 0
PK of MA-20 in serum: Apparent terminal elimination rate constant (Kel)
Timepoint [10] 0 0
Up to 26 months
Secondary outcome [11] 0 0
PK of MA-20 in serum: Clearance (CL)
Timepoint [11] 0 0
Up to 26 months
Secondary outcome [12] 0 0
Number of participants with positive anti-drug antibodies to MA-20
Timepoint [12] 0 0
Up to 26 months
Secondary outcome [13] 0 0
Objective Response Rate (ORR) of ASP2802 per Lugano Response Criteria
Timepoint [13] 0 0
Up to 26 months
Secondary outcome [14] 0 0
Best Overall Response (BOR) of ASP2802 per Lugano Response Criteria
Timepoint [14] 0 0
Up to 26 months
Secondary outcome [15] 0 0
Duration of Response (DOR) of ASP2802 per Lugano Response Criteria
Timepoint [15] 0 0
Up to 26 months
Secondary outcome [16] 0 0
Progression Free Survival (PFS) of ASP2802
Timepoint [16] 0 0
Up to 26 months
Secondary outcome [17] 0 0
Overall Survival (OS) of ASP2802
Timepoint [17] 0 0
Up to 88 months

Eligibility
Key inclusion criteria
* Participant has histologically-confirmed cluster of differentiation (CD) 20-positive B-cell lymphoma (CD20 expression should be demonstrated by local testing at the time of relapse or progression and within 1 month of study screening) which may include the following aggressive large cell or indolent subtypes.

* Diffuse large B-cell lymphoma (DLBCL), Not otherwise specified (NOS)
* Follicular lymphoma grade 3B
* Primary mediastinal large B-cell lymphoma
* T-cell/histiocyte-rich large B-cell lymphoma
* DLBCL associated with chronic inflammation
* Intravascular large B-cell lymphoma
* Anaplastic lymphoma kinase fusion gene (ALK)+ large B-cell lymphoma
* B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
* High grade B-cell lymphoma with proto-oncogene located on chromosome 8 (MYC) and B-cell leukemia/lymphoma 2 gene (BCL2) and/or B-cell leukemia/lymphoma 6 gene (BCL6) rearrangements
* High-grade B-cell lymphoma, NOS
* Human herpes virus type 8 (HHV8)+ DLBCL, NOS
* Primary cutaneous DLBCL, leg type
* Transformed follicular lymphoma
* Follicular lymphoma
* Marginal zone lymphoma
* Participant has either relapsed or refractory disease defined as:

* Relapse after = 2 prior lines of therapy; or
* Refractory disease: After = 2 prior lines of therapy and did not achieve complete response (CR)
* Participants who have undergone autologous stem cell transplant (SCT) with disease progression or relapse following SCT will be eligible if all other eligibility criteria are met.
* Participants with lymphoma must have evaluable or measurable disease according to the Lugano criteria for response assessment of lymphoma. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
* At least 2 weeks or 5 half-lives, whichever is longer, must have elapsed since any prior anticancer therapy at the time of leukapheresis, except for inhibitory/stimulatory immune checkpoint therapy, which requires 3 half-lives.

Exceptions:

* There is no time restriction with regard to prior intrathecal chemotherapy (including steroids) provided there is complete recovery from any acute toxic effects of such.
* Participants receiving steroid therapy at physiologic replacement doses (= 5 milligrams per day (mg/day) of prednisone or equivalent doses of other corticosteroids) are allowed. Use of higher doses of systemic steroids must stop at least 72 hours before leukapheresis.
* Radiation therapy must have been completed at least 2 weeks prior to leukapheresis.

* Toxicities due to prior therapy must be stable and recovered to = Grade 1 (except for clinically non-significant toxicities, such as alopecia, nutritional support measures, electrolyte abnormalities or those not impacting the investigator's ability to assess treatment-emergent toxicities).
* Participant has cardiac ejection fraction (EF) = 45%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram or multigated acquisition scan (MUGA) and no clinically significant ECG findings.
* Participant has no clinically significant pleural effusion.
* Participant has baseline oxygen saturation > 90% on room air at rest.
* Participant has a life expectancy of = 12 weeks.
* Participant has an ECOG performance score of 0, 1 or 2.
* Female participant is not pregnant and at least 1 of the following conditions apply:
* Not a woman of childbearing potential (WOCBP).
* WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after final study treatment administration.

* Female participant must agree not to breastfeed starting at screening and throughout the study period and for 6 months after final study treatment administration.
* Female participant must not donate ova starting at first dose of IP and throughout the study period and for 6 months after final study treatment administration.
* Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 6 months after final study treatment administration.
* Male participant must not donate sperm during the treatment period and for 6 months after final study treatment administration.
* Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 6 months after final study treatment administration.
* Participant agrees not to participate in another interventional study while participating in the present study
* Participant has adequate organ function at baseline. If a participant has received a recent blood transfusion, the laboratory tests must be obtained = 28 days after any blood transfusion.

Additional Inclusion Criteria prior to Lymphodepletion Chemotherapy:

* Participant has adequate hepatic function defined by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 × upper limit of normal (ULN); total bilirubin = 1.5 × ULN (participants with Gilbert's syndrome may be included if their total bilirubin is = 3.0 × ULN and direct bilirubin is = 1.5 × ULN)
* Participant has adequate renal function defined by:

* Creatinine < 1.5 × ULN, or
* An estimated creatinine clearance (CrCl) of = 60 milliliter per minute (ml/min) as calculated by the Cockcroft-Gault equation
* Participant has adequate bone marrow function defined by absolute neutrophil count = 500/microliter (µl) and platelet count = 50 000/µl (unless inadequate bone marrow function is thought to be related to bone marrow involvement with the lymphoproliferative neoplasm).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participant has been diagnosed with the following conditions:

* B-lymphoblastic leukemia/lymphoma (B-ALL/LBL)
* chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
* Burkitt lymphoma
* Richter's transformation of CLL/SLL
* Epstein-Barr virus (EBV)+ DLBCL, NOS
* Mantle cell lymphoma
* Known history or suspicion of central nervous system involvement by lymphoma.
* Participant weighs < 45 kilograms (kg) at screening.
* Participant had prior allogeneic hematopoietic stem cell transplantation (HSCT).
* Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening.
* Participant has a history of non-study related malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) unless disease free for at least 3 years.
* Participant has a history of myocardial infarction, cardiac angioplasty or stenting, unstable angina or other clinically significant cardiac disease within 12 months of enrollment or has cardiac atrial or cardiac ventricular lymphoma involvement.
* Participant has known abnormal lung function: forced expiratory volume (FEV) < 60% prediction, diffusing capacity of the lung for carbon monoxide < 60% prediction, blood oxygen saturation < 90% on room air.
* Participant has intracranial hypertension or unconsciousness, respiratory failure or disseminated intravascular coagulation.
* Participant has leukocytosis (white blood cell [WBC] count = 25 000/µL) or rapidly progressive disease that would compromise ability to complete study therapy.
* Participant has a history or presence of a central nervous system (CNS) disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, seizure disorder or autoimmune disease with CNS involvement that may impair the ability to evaluate neurotoxicity.
* Participant has any of the following per screening serology test:

* Hepatitis A virus (HAV) antibodies immunoglobulin M (IgM)
* Positive hepatitis B surface antigen (HBsAg) or detectable hepatitis B Deoxyribonucleic acid (DNA). Participants with negative HBsAg, positive hepatitis B core antibody (anti-HBc) and negative anti-HBs are eligible if hepatitis B DNA is undetectable
* hepatitis C virus (HCV) antibodies unless HCV ribonucleic acid (RNA) is undetectable
* Participant has human immunodeficiency virus (HIV) per screening serology test.
* Participant has a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) test at Screening.
* Participant has a primary immunodeficiency or history of systemic autoimmune disease (e.g., Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/disease-modifying agents within the last 2 years.
* Participant has presence of fungal, bacterial (e.g., tuberculosis), viral or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple infections like urinary tract infections and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
* Participant's adverse reactions (excluding alopecia or vitiligo) from prior therapy have not improved to Grade 1 or baseline at least 14 days prior to Screening.
* Participant has received rituximab within 14 days prior to Screening.
* Participant has presence of any other concurrent medical condition or factors that would prevent the participant from undergoing or completing protocol-specified treatment, or makes the participant unsuitable for study participation.
* Participant had prior treatment with CD20 CAR-T cell or CD20 bi-specific therapy.
* Participant has a known or suspected hypersensitivity to ASP2802 (MACT), MA-20, fludarabine, cyclophosphamide or any components of the formulations used.
* Participant is receiving treatment with anticoagulants.

Additional Exclusion Criteria required for Lymphodepletion Chemotherapy:

* Participant received bridging therapy within 10 days prior to start of lymphodepletion chemotherapy (LDC).
* Participant has an active systemic infection present or onset of fever = 38°C/100.4°F, not related to underlying disease. Participants who meet either of these on the day of scheduled ASP2802 (MACT) infusion should have ASP2802 (MACT) administration delayed.
* Participant has a positive SARS-CoV-2 PCR test.
* Participant has an intercurrent illness or toxicity that would place the participant at undue risk of proceeding to LDC and ASP2802 (MACT) infusion.
* Participant is receiving therapeutic doses of corticosteroids (defined as = 20 mg/day prednisone or equivalent) within 24 hours prior to LDC. Physiologic replacement, topical, intranasal and inhaled steroids are permitted.
* Participant has signs of pre-existing CNS disease or toxicity.
* Participant has had major surgery within 28 days prior to the start of study treatment.
* Participants should not experience a significant worsening in clinical status compared to initial eligibility criteria that would increase the risk of adverse events associated with LDC or ASP2802 (MACT) infusion.

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

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Site AU61008 - Camperdown
Recruitment hospital [2] 0 0
Site AU61004 - Fitzroy
Recruitment hospital [3] 0 0
Site AU61005 - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
- Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Astellas Pharma Global Development, Inc.
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Central Contact
Address 0 0
Astellas Pharma Global Development, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Astellas Pharma Global Development, Inc.
Address 0 0
Country 0 0
Phone 0 0
800-888-7704
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
Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."


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.