A Phase 1/2 Dose-Escalation and Dose-Expansion of the Safety and Efficacy of Anti-CD7 Allogeneic CAR-T cells (WU-CART-007) in Patients with Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia /Lymphoblastic Lymphoma (T-ALL)/Lymphoblastic Lymphoma (LBL)
The main purpose of this study is to evaluate the safety, recommended dose, and preliminary anti-tumor activity of WU-CART-007 in patients with relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (LBL).
Primary Objectives: To characterize the safety, tolerability, DLT, and MTD or MAD (if no MTD is defined) and define the RP2D of WU-CART-007 in T-ALL/LBL (Phase 1). To investigate the preliminary anti-tumor activity, as measured by objective response rate (ORR) and duration of response (DOR) of WU-CART-007 in relapsed or refractory (R/R) T-ALL/LBL patients (Phase 2). ORR is defined as proportion of patients that achieve CR + CRi. Secondary Objectives: 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 HCT in eligible patients. Exploratory Objectives: To valuate persistence and immunophenotype (cellular kinetics) of WU-CART-007 in blood and bone marrow over time. To evaluate the immunogenicity of WU-CART-007 i.e., development of anti-CAR antibodies. To understand the assessment of CD7 expression as it relates to clinical response in the treatment of relapsed or refractory T-ALL/LBL as measured by flow cytometry. To explore the tumor microenvironment (TME) by measuring mRNA and protein levels of immune markers before and after treatment with WU-CART-007 in T-ALL/LBL. To evaluate cytokines/chemokines levels before, during and after treatment with WU-CART-007. To evaluate utility of MRD, in subjects achieving a CR, in the context of WU-CART-007 treatment in T-ALL/LBL.
Cell Therapy; Chemotherapy (NOS)
Cladribine (); WU-CART-007 (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)
- 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:
- 1. Primary refractory: failure to achieve CR after induction chemotherapy, per investigator.
- 2. Early Relapse: relapsed disease within 12 months of initial diagnosis.
- 3. Late Relapse (relapsed refractory disease): relapsed disease after 12 months of initial diagnosis AND failure of re-induction therapy after disease recurrence.
- 4. 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 veno-occlusive disease (VOD), or active graft versus host disease (GvHD) (see exclusion criteria below for exceptions).
- Adequate renal, hepatic, respiratory, and cardiovascular function, as defined in the body of the protocol.
- Life expectancy >12 weeks
- Ability to understand the nature of this study, comply with protocol requirements, and give written informed consent.
- Willing to participate in WUC-007-02 for long-term follow up.
- 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
- Treated with anti-T cell monoclonal antibodies (except daratumumab)
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