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

Lymphoblastic Lymphoma Clinical Trial

Official title:

A Phase 1/2 Dose-Escalation and Dose-Expansion Study 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 (T-ALL)/Lymphoblastic Lymphoma (LBL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04984356
• Other study ID #: WU-CART-007 1001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: January 14, 2022
• Est. completion date: August 2026

Study information

• Verified date: September 2023
• Source: Wugen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 44
• Est. completion date: August 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Key Inclusion/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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Lymphoblastic Lymphoma
• Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• T-cell Acute Lymphoblastic Leukemia

Intervention

Biological:
• WU-CART-007
A single IV infusion of WU-CART-007 Cells on Day 1

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
France	Hospital Saint- Louis	Paris
France	University Hospital Robert Debre	Paris
Netherlands	Erasmus MC	Rotterdam
Netherlands	Prinses Maxima Centrum	Utrecht
United States	City of Hope	Duarte	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Vanderbilt University	Nashville	Tennessee
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Moffit Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Wugen, Inc.

Countries where clinical trial is conducted

United States,  Australia,  France,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events of WU-CART-007 as assessed by CTCAE v5	Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of consent until end of study visit	24 months
Primary	Maximum Tolerated Dose (MTD)	Maximum tolerated or administered dose of WU-CART-007	up to 28 days from first dose
Primary	Composite Complete Response Rate	Defined as proportion of patients that achieve a complete remission (CR) + complete remission with incomplete hematologic recover ( CRi) + CR with partial hematologic recovery (CRh)	24 months
Secondary	Overall Survival	Time from study drug administration (Day 1) to death on study	24 months
Secondary	Objective Response Rate	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	24 months
Secondary	Duration of Response	Time of response to the time of disease relapse, progression or death due to any cause. whichever occurs first	24 months
Secondary	Hematopoietic Stem Cell Transplant (HSCT) rate	Rate of successful transition to HSCT through study treatment	24 months