A Phase 1/2 Study of the Safety and Efficacy of Anti-CD7 Allogeneic CAR-T Cells (WU-CART-007) in Patients With Relapsed or Refractory T-ALL/LBL

Phase 1

Completed

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

• Registration Number: NCT04984356
• Lead Sponsor: Wugen, Inc.

Brief Summary

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).

Detailed Description

This is a first-in-human, multicenter, Phase 1/2, single-agent study in patients with R/R T-ALL/T-LBL who have exhausted other treatment options. The study will consist of two phases, Phase 1 and Phase 2. During the Dose Escalation segment (Phase 1) up to 24 patients will be treated with 1 dose of WU-CART-007, in up to 4 dose levels until maximum tolerated dose (MTD) or maximum administered dose (MAD) is determined. The dose escalation segment will enroll successive cohorts of 3 to 6 patients using a standard 3 + 3 design. Once the recommended phase 2 dose (RP2D) is defined, the Phase 2 portion (Cohort Expansion) will enroll expansion cohorts.

Study Timeline

• Study First Submitted: 2021-07-29
• Study First Submitted QC: 2021-07-29
• Study First Posted: 2021-07-30
• Study Start: 2022-01-14
• Primary Completion: 2024-06-01
• Study Completion: 2024-06-01
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-19
• Last Update Posted: 2024-11-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

Not provided

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Exclusion Criteria

Specific inclusion criteria apply to each disease subtype. In general, all patients will have:

• 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 Grade 2 or greater (per Cairo-Bishop) veno-occlusive disease (VOD)/sinusoidal obstruction syndrome, 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
• Age: Lower age limit of 12 years. Adolescent ages 12-17 will be eligible for enrollment beginning at Dose Level 3 of the Dose Escalation phase, after review of safety, efficacy and cellular PK 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.

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 and all related toxicities resolved to Grade 1 or baseline.
• 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

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
Maximum Tolerated Dose (MTD)	up to 28 days from first dose	Maximum tolerated or administered dose of WU-CART-007
Incidence of Adverse Events of WU-CART-007 as assessed by CTCAE v5	24 months	Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of consent until end of study visit
Composite Complete Response Rate	24 months	Defined as proportion of patients that achieve a complete remission (CR) + complete remission with incomplete hematologic recover ( CRi) + CR with partial hematologic recovery (CRh)

Secondary Outcome Measures

Name	Time	Method
Overall Survival	24 months	Time from study drug administration (Day 1) to death on study
Objective Response Rate	24 months	ORR is defined as proportion of patients that achieve complete remission (CR) + complete remission with incomplete hematologic recover ( CRi) + CR with partial hematologic recovery (CRh), morphologic leukemia free state (MLFS, and partial response (PR) in patients with EMD only
Hematopoietic Stem Cell Transplant (HSCT) rate	24 months	Rate of successful transition to HSCT through study treatment
Duration of Response	24 months	Time of response to the time of disease relapse, progression or death due to any cause. whichever occurs first

Trial Locations

Locations (12)

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

University Hospital Robert Debre; 🇫🇷 Paris, France

Prinses Maxima Centrum; 🇳🇱 Utrecht, Netherlands

Moffit Cancer Center; 🇺🇸 Tampa, Florida, United States

Vanderbilt University; 🇺🇸 Nashville, Tennessee, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

University of Wisconsin; 🇺🇸 Madison, Wisconsin, United States

City of Hope; 🇺🇸 Duarte, California, United States

Hospital Saint- Louis; 🇫🇷 Paris, France

Erasmus MC; 🇳🇱 Rotterdam, Netherlands