A Phase 2 Study WU-CART-007 in T-Cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Phase 2

Not yet recruiting

• Conditions: T-cell Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma
• Interventions: Biological: WU-CART-007

• Registration Number: NCT06514794
• Lead Sponsor: Wugen, Inc.

Brief Summary

The main purpose of this study is to evaluate the Composite Complete Remission Rate (CRc) of WU-CART-007 in Relapsed/Refractory (R/R) T-Cell Acute Lymphoblastic Leukemia (T-ALL)/Lymphoblastic Lymphoma (LBL) patients and to evaluate the efficacy of WU-CART-007 to induce complete Minimum Residual Disease (MRD) negative response

Detailed Description

This is a Phase 2, single-agent study in patients with R/R T-ALL/LBL and T-ALL/LBL in remission but remaining MRD positive.

The study is divided into 2 disease Cohorts. The Relapsed/Refractory (R/R) Cohort will evaluate patients with relapsed or refractory disease, defined as ≥5% blast in the BM and/or extramedullary disease (EMD) only. The Minimal Residual Disease (MRD) Positive Cohort will evaluate patients in complete remission with MRD positive disease (0.01-\< 5% blasts in the BM)

Enrollment will begin with a safety lead-in for both cohorts (R/R and MRDpos) at a reduced dose to confirm that the safety data obtained from adults and adolescents demonstrated in the Phase 1/2 trial is comparable for pediatric patients ages 1-11. This lead-in will also include a group of patients ages 12 and older to validate the prior safety data and serve as control for the lead-in patients ages 1-11. There will be at least 12 patients that participate in the safety lead-in (three patients younger than 12 years old and three aged 12 or older in each cohort).

Study Timeline

• Study First Submitted: 2024-07-17
• Study First Submitted QC: 2024-07-17
• Study First Posted: 2024-07-23
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-19
• Last Update Posted: 2024-11-20
• Study Start: 2024-12-13
• Primary Completion: 2026-12-30
• Study Completion: 2028-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 125

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
WU-CART-007	WU-CART-007	A CD7-directed chimeric antigen receptor (CAR) T-cell product. A single IV infusion of WU-CART-007 Cells on Day 1 after Lymphodepletion(LD) Therapy.

Primary Outcome Measures

Name	Time	Method
R/R Cohort - Composite Complete Response Rate	24 months	CRc is defined as proportion of patients that achieve a complete remission (CR) + CR with incomplete hematologic recovery (CRi)
MRD Pos Cohort - Response Rate	24 months	Defined as the efficacy of WU-CART-007 to induce complete MRD negative response

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate	24 months	ORR is defined as proportion of patients that achieve CR + CRi, and partial response (PR) in patients with EMD only (R/R Cohort)
MRD Response Rate (R/R Cohort)	24 months	Defined as the efficacy of WU-CART-007 to induce complete MRD response as determined by central flow-based MRD assay (R/R Cohort)
Duration of Response	24 months	Time of response to the time of disease relapse and/or change in MRD status
Overall Survival	24 months	Time from study drug administration (Day 1) to death on study
Hematopoietic Stem Cell Transplant (HSCT) rate	24 months	Rate of successful HSCT through study treatment