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)
- Conditions
- Leukemia (TALL) / Lymphoma (LBL)10024324
- Registration Number
- NL-OMON53869
- Lead Sponsor
- Wugen, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 4
• 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:
a. Primary refractory: failure to achieve CR after induction chemotherapy, per
investigator.
b. Early Relapse: relapsed disease within 12 months of initial diagnosis.
c. Late Relapse (relapsed refractory disease): relapsed disease after 12 months
of initial diagnosis AND failure of re-induction therapy after disease
recurrence.
d. 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), 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. Adolescents ages 12-17 will be eligible for
enrollment based on:
o The recommendation and approval of the DSC following review of safety
data and clinical benefit from prior and current dose levels.
o Consultation with the appropriate regulatory agencies after submission
of the aforementioned data.
• 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.
• 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 antineoplastic
agents (fully defined in Section 6.2 criterion # 13.
• Treated with anti-T cell monoclonal antibodies
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Objectives<br /><br><br /><br>• To characterize the safety, tolerability, dose-limiting toxicities (DLT),<br /><br>and maximum tolerated dose (MTD) or maximum administered dose (MAD)<br /><br>(if no MTD is defined) and define the Recommended Phase 2 Dose (RP2D) of<br /><br>WU-CART-007 in T-ALL/LBL (Phase 1).<br /><br><br /><br>• To investigate the preliminary anti-tumor activity, as measured by<br /><br>objective response rate (ORR) of WU-CART-007 in relapsed/refractory (R/R)<br /><br>T-ALL/LBL patients (Phase 2).<br /><br>ORR is defined as proportion of patients that achieve CR), CRh, CRi,<br /><br>morphologic leukemia free state (MLFS), and partial response (PR) in patients<br /><br>with EMD only (Phase 2).</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Objectives<br /><br><br /><br><br /><br>• To investigate the Complete Remission Rate (CRR) of WU-CART-007 in R/R<br /><br>T-ALL/LBL patients. CRR is defined as proportion of patients that<br /><br>achieve a complete remission (CR) + CR with partial hematologic recovery<br /><br>(CRh) + CR with incomplete hematologic recovery (CRi).<br /><br>• To investigate the duration of response (DOR) of WU-CART-007 in R/R T-ALL/LBL<br /><br>patients.<br /><br>• To investigate the preliminary effect on overall survival (OS) and<br /><br>progression-free survival (PFS)<br /><br>• To evaluate preliminary anti-tumor activity as measured by CR rate defined as<br /><br>proportion of patients that achieve a CR<br /><br>• To determine rate of successful transition to hematopoietic cell transplant<br /><br>(HCT) in eligible patients</p><br>