A Phase 2 Study of WU-CART-007, an Anti-CD7 Allogeneic CAR-T Cell Therapy inT-Cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Inclusion Criteria

• Disease Criteria: Evidence of T-ALL or T-LBL, as defined by World Health Organization (WHO) classification, and either relapse/refractory or MRD positive, defined as:

  • Relapsed or Refractory Cohort: disease defined by bone marrow with ≥5% lymphoblasts by morphologic assessment or flow cytometry or evidence of extramedullary disease (EMD). Patients must also be characterized by at least one of the following criteria:

    • Primary refractory: failure to achieve remission after bona fide induction attempt which may include consolidation.
    • Early Relapse: relapsed disease within 24 months of initial diagnosis.
    • Late Relapse (relapsed refractory disease): relapsed disease after 24 months of initial diagnosis AND failure of re- induction therapy after disease recurrence.
    • Relapsed or refractory disease after allogeneic transplant,

  • Minimal Residual Disease (MRD) Cohort: evidence of MRD, defined as < 5% blasts in bone marrow but ≥ 0.01% blasts determined by central laboratory flow cytometry assay, and characterized by at least one of the following criteria:

    • Failure to reach MRD negative status following induction and consolidation in frontline therapy or reinduction for relapse.
    • MRD positive disease following allogeneic HSCT.

• Adequate Organ Function as defined as:

  • Hepatic and renal function:

    • Hepatic transaminase (both alanine aminotransferase and aspartate aminotransferase) levels ≤5 times the institutional upper limit of normal (ULN),
    • Total bilirubin level ≤1.5 times the ULN (unless the patient has a history of Gilbert's Syndrome, in which case, total bilirubin must be ≤2.5 times the ULN),
    • Serum creatinine level ≤1.5 times the ULN or a calculated or measured creatinine clearance of ≥50 ml/min.

  • Respiratory function: Must have a minimum level of pulmonary reserve defined as pulse oxygenation >91% on room air.

  • Cardiovascular function: left ventricular ejection fraction ≥45% for adults or shortening fraction ≥ 28% for pediatric patients confirmed by echocardiogram or MUGA within 28 days of Screening.

• Age: Lower age limit of ≥ 1 year.

• Eastern Cooperative Oncology Group (ECOG)/Karnofsky Performance Status 0 or 1/60 and above at Screening (Adults age > 16) or Lansky Performance Status 60 and above (pediatrics/ adolescents age ≤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 WUC007-02 for long term follow-up.

Exclusion Criteria

• Patients who meet any of the following criteria will be excluded from study entry:

  • Treatment with any prior anti-CD7 therapy.
  • Unresolved toxicities from prior anticancer therapy, defined as having not resolved to baseline or to CTCAE Grade ≤1, except for nausea or alopecia, or to the levels dictated in the inclusion/exclusion criteria.
  • Patients with hypersensitivity to cyclophosphamide or fludarabine, their excipients, or cyclophosphamide metabolites.
  • Patients with urinary outflow obstruction and acute urothelial toxicity from prior chemotherapy or radiation.
  • Patients with decompensated hemolytic anemia.
  • Active or latent hepatitis B or active hepatitis C, or any uncontrolled infection
  • HIV positive test within 8 weeks of planned treatment initiation.
  • Serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
  • Presence of Grade 2 to 4 acute or extensive chronic GvHD requiring systemic immunosuppression (e.g. steroids). Grade 1 GvHD not requiring immunosuppression or Grade 2 skin GvHD if treated with topical therapy only are acceptable.
  • Presence of other active cancers, or history of treatment for invasive cancer ≤3 years.
  • Patients with active central nervous system (CNS) leukemia involvement defined as CNS-3 are not eligible unless CNS leukemia is reduced to CNS2 or CNS1.
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  • Pregnant or nursing (lactating) women.
  • Patient with rapidly progressive disease that in the opinion of the investigator may put the patient at increased risk of toxicities.
  • Requires prohibited medication or treatments e.g. steroids, or anti-neoplastic agents.