Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia MedDRA version: 21.0 Level: PT Classification code 10042987 Term: T-cell type acute leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 22.0 Level: PT Classification code 10029547 Term: Non-Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: WU-CART-007
Product Code: WU-CART-007
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: CAR+ve T cells
Other descriptive name: WU-CART-007
Concentration unit: million or
Sponsors
Wugen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Evidence of relapsed or refractory T-ALL or T-LBL, as defined by World Health Organization (WHO) classification with bone marrow with = 5% lymphoblasts by morphologic assessment or evidence of extramedullary disease at screening. • Relapsed or refractory disease defined as at least one of the following criteria: a. Primary refractory: failure to achieve CR after induction chemotherapy, per investigator. b. Early Relapse: relapsed disease within 12 months of initial diagnosis. c. Late Relapse (relapsed refractory disease): relapsed disease after 12 months of initial diagnosis AND failure of re-induction therapy after disease recurrence. d. Relapsed or refractory disease after allogeneic transplant, and meet the following criteria: i. There must be histological confirmation of relapse after HSCT of T-ALL or T-LBL. ii. Undergone allogeneic HSCT > 90 days prior to enrollment from a match related or unrelated donor, cord blood donor, haplo-identical, or autologous stem cells. iii. Off all immunosuppressive medications for a minimum of 2 weeks with the exception of physiologic doses of corticosteroids, iv. No prior history of Grade 2 or greater (per Cairo-Bishop) veno-occlusive disease/sinusoidal obstruction syndrome (VOD), or active graft versus host disease (GvHD) see Exclusion Criteria 8 below for exceptions. • Adequate renal, hepatic, respiratory, and cardiovascular function, as defined in the body of the protocol. • Life expectancy >12 weeks • Age: Lower age limit of 12 years. Adolescent ages 12 to 17 will be eligible for enrollment beginning at Dose Level 3 of the dose-escalation phase, after review of safety, efficacy and cPK data and after consultation with the appropriate regulatory agencies. • ECOG/Karnofsky performance status 0 or 1 at screening (Adults age >16) or Lansky Performance Status 60 and above (adolescents = 16), • Ability to understand the nature of this study, comply with protocol requirements, and give written informed consent. For minors, legal guardian willingness to give written informed consent with patient assent, where appropriate. • Willing to participate in WUC-007-02 for long-term follow up. Are the trial subjects under 18? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: Patients will be excluded from study entry if: • They have received previous treatment with any prior anti-CD7 therapy. • Have not recovered from the effects of previous therapy. • Wash-out period of at least 5 half-lives from the last dose of any investigational therapy prior to screening period. • Have active or latent hepatitis B or active hepatitis C, any uncontrolled infection, or untreated HIV positive. • Have any serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. • Have Grade 2 to 4 acute or extensive chronic GvHD requiring systemic immunosuppression (steroids). Grade 1 GvHD not requiring immunosuppression is acceptable and grade 2 skin GvHD if treated with topical therapy only is acceptable. • Have psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. • Pregnant or nursing (lactating) women • Require prohibited medications or treatments, eg, steroids, or anti-neoplastic agents (fully defined in Section 6.2 criterion # 13. • Treated with anti-T cell monoclonal antibodies
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To characterize the safety, tolerability, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) and define the Recommended Phase 2 Dose (RP2D) of WU-CART-007 in T-ALL/LBL (Phase 1). • To investigate the preliminary anti-tumor activity, as measured by complete response rate (CRR), objective response rate (ORR) and duration of response (DOR) of WU-CART-007 in relapsed/refractory (R/R) T-ALL/LBL patients (Phase 2). CRR is defined as proportion of patients that achieve a complete remission (CR) + CR with partial hematologic recovery (CRh) + CR with incomplete hematologic recovery (CRi). ORR is defined as proportion of patients that achieve CR), CRh, CRi, morphologic leukemia free state (MLFS), and partial response (PR) in patients with EMD only;Secondary Objective: • To investigate the preliminary effect on overall survival (OS) and progression-free survival (PFS). • To evaluate preliminary anti-tumor activity as measured by Complete Remission (CR) rate defined as proportion of patients that achieve a CR. • To determine rate of successful transition to hematopoietic cell transplant (HCT) in eligible patients.;Primary end point(s): 1. Assessment of safety and tolerability and DLT 2. Establishment of MTD or MAD 3. Investigate preliminary anti-tumor activity;Timepoint(s) of evaluation of this end point: No formal interim analysis is planned, as this is an open label trial. The final analysis of the study will occur when the first of either 1 of the following circumstances occurs: • The last patient completes treatment with a minimum of 3-month follow up; • Three years following the enrollment of the first patient. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Preliminimary effect on overall survival (OS) and progression-free survival (PFS) 2. Preliminary anti-tumor activity as measured by Complete Remission 3. Determine rate of successful transition to HCT in eligible patients;Timepoint(s) of evaluation of this end point: No formal interim analysis is planned, as this is an open label trial. The final analysis of the study will occur when the first of either 1 of the following circumstances occurs: • The last patient completes treatment with a minimum of 3-month follow up; • Three years following the enrollment of the first patient. | — |
Countries
Australia, France, Germany, Netherlands, United Kingdom, United States
Contacts
Public ContactEileen Mcnulty
Wugen, Inc.
Outcome results
None listed