Dose-Escalation and Dose-Expansion Study to Evaluate the Safety and Tolerability of Anti-CD7 Allogeneic CAR T-Cells (WU-CART-007) in Patients With CD7+ Hematologic Malignancies

NCT05377827 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202306200
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Effective treatment options for relapsed/refractory acute myeloid leukemia (AML) and T-cell non-Hodgkin lymphoma (T-NHL) represent a significant unmet medical need. CAR T therapy has offered durable remissions and potential cures in some forms of hematologic malignancy, including B-cell acute lymphoblastic leukemia. In AML, however, CAR T approaches have been limited by the lack of suitable antigens, as most myeloid markers are shared with normal hematopoietic stem cells and targeting of these antigens by CAR T therapy leads to undesirable hematologic toxicity. Similarly, T-NHL has not yet benefited from CAR T therapy due to a lack of suitable markers. One potential therapeutic target is CD7, which is expressed normally on mature T-cells and NK-cells but is also aberrantly expressed on \~30% of acute myeloid leukemias. CAR T therapy for patients with CD7+ AML and T-NHL will potentially offer a new therapeutic option which has a chance of offering durable benefit. WU-CART-007 is a CD7-directed, genetically modified, allogeneic, fratricide-resistant chimeric antigen receptor (CAR) T-cell product for the treatment of CD7+ hematologic malignancies. These cells have two key changes from conventional, autologous CAR T-cells. First, because CD7 is present on normal T-cells including conventional CAR T products, CD7 is deleted from WU CART-007. This allows for targeting of CD7 without the risk of fratricide (killing of WU-CART-007 cells by other WU-CART-007 cells). Second, the T cell receptor alpha constant (TRAC) is also deleted. This makes WU CART 007 cells incapable of recognizing antigens other than CD7 and allows for the use of an allogeneic product without causing Graft-versus-Host-Disease (GvHD).

Conditions

T-Cell Non-Hodgkin Lymphoma; Acute Myeloid Leukemia; Angioimmunoblastic T-cell Lymphoma; Enteropathy-Associated T-Cell Lymphoma; Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma; Peripheral T Cell Lymphoma; Anaplastic Large Cell Lymphoma; Adult T Cell Leukemia; Adult T Cell Lymphoma; T Cell Prolymphocytic Leukemia; Extranodal NK/T-cell Lymphoma; Transformed Mycosis Fungoides; Sezary Syndrome; Primary Cutaneous Gamma-Delta T-Cell Lymphoma; Hepatosplenic T-cell Lymphoma

Outcome Measures

Primary Outcomes (3)

• Recommended phase II dose (Dose Escalation only)

  -The recommended phase II dose (RP2D) will be determined independently for each disease cohort (CD7+ AML and T-NHL). The RP2D will not be greater than the maximum tolerated dose (MTD). However, the RP2D may be a lower dose level in certain circumstances: * If emerging toxicity at the MTD is unpredictable or undesirable for other reasons. * If clear evidence of efficacy is noted at lower doses with a cleaner safety profile. * If the cellular pharmacokinectic (cPK) profile that emerges results in similar numbers of clonal cells over time that is independent of administered dose level. * If longer follow-up on earlier patient cohorts suggests the emergence of delayed toxicity.

  Through completion of day 42 for all Part A participants (estimated to be 18 months and 42 days)

• Number of participants with complete metabolic response or partial metabolic response (Dose expansion only - Cohort A)

  -Per Lugano criteria for patients with T-cell lymphoma (T-NHL). Per Global Response Criteria for cutaneous T-cell lymphoma (CTCL). Per the T-PLL International Study Group criteria for T-cell prolymphocytic leukemia (T-PLL)

  Through completion of response assessments (estimated to be 24 months)

• Number of participants with complete remission, complete remission with incomplete blood count recovery, complete remission with partial hematologic recovery, or morphologic leukemia free state (Dose expansion only - Cohort B)

  -Per modified 2017 ELN criteria for patients with AML

  Through completion of response assessments (estimated to be 24 months)

Secondary Outcomes (7)

• Number of participants with treatment-emergent adverse events as measured by CTCAE v 5.0

  From start of treatment through completion of follow-up (estimated to be 24 months)

• Number of participants with cytokine release syndrome

  From start of treatment through Day 7 (estimated to be 8 days)

• Number of participants with immune effector cell-associated neurotoxicity syndrome (ICANS) as measured by ASTCT Consensus Grading

  From start of treatment through Day 7 (estimated to be 8 days)

• Duration of remission (DoR) (Dose Expansion only)

  Through completion of response assessments (estimated to be 24 months)

• Relapse-free survival (RFS) (Dose Expansion only)

  Through completion of follow-up (estimated to be 24 months)

Study Arms (4)

Dose Escalation Cohort A: WU-CART-007 T-NHL

EXPERIMENTAL

Patients will receive preparative lymphodepletion in the week prior to WU-CART-007, after which WU-CART-007 will be infused 3 days following the last dose of chemotherapy at the assigned dose level.

Dose Escalation Cohort B: WU-CART-007 leukemia

EXPERIMENTAL

Patients will receive preparative lymphodepletion in the week prior to WU-CART-007, after which WU-CART-007 will be infused 3 days following the last dose of chemotherapy at the assigned dose level.

Dose Expansion Cohort A: WU-CART-007 T-NHL

EXPERIMENTAL

Patients will receive preparative lymphodepletion in the week prior to WU-CART-007, after which WU-CART-007 will be infused 3 days following the last dose of chemotherapy at the recommended phase II dose.

Dose Expansion Cohort B: WU-CART-007 leukemia

EXPERIMENTAL

Patients will receive preparative lymphodepletion in the week prior to WU-CART-007, after which WU-CART-007 will be infused 3 days following the last dose of chemotherapy at the recommended phase II dose.

Interventions

WU-CART-007 BIOLOGICAL

Provided by Miltenyi Biotec

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will have T-cell non-Hodgkin lymphoma with relapsed or refractory disease defined as one of the following:
• Relapsed or refractory after at least 2 or more prior lines of therapy (for patients with anaplastic large cell lymphoma, they must have prior therapy brentuximab vedotin). For patients with T-PLL, only 1 or more prior line of therapy is required. OR
• Relapsed after autologous or allogeneic hematopoietic cell transplant.
• Permissible T-cell NHL subtypes will include:
• angioimmunoblastic T-cell lymphoma (AITL)
• enteropathy-associated T-cell lymphoma (EATL)
• monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL)
• peripheral T-cell lymphoma (PTCL) NOS
• anaplastic large cell lymphoma (ALCL)
• adult T-cell leukemia/lymphoma
• T-cell prolymphocytic leukemia (T-PLL)
• extranodal NK/T cell lymphoma
• transformed mycosis fungoides/Sezary Syndrome
• primary cutaneous gamma/delta T-cell lymphoma
• hepatosplenic T cell lymphoma

You may not qualify if:

• Patients will be excluded from study entry for any of the following:
• Received systemic anticancer therapy (including investigational therapy) or radiotherapy \< 28 days or 5 half-lives, whichever is shorter, prior to the start of lymphodepleting chemotherapy with the exception of bridging treatment as defined by protocol.
• Received any T-cell lytic or toxic antibody (e.g., alemtuzumab) within 8 weeks prior to lymphodepleting chemotherapy.
• Subjects who have received a prior allogeneic HCT are excluded if any of the following criteria are present:
• \< 100 days post alloHCT
• \< 6 weeks from prior donor leukocyte infusion
• Presence of acute or extensive chronic GVHD requiring systemic immunosuppression except for prednisone ≤ 10 mg or equivalent.
• \< 28 days from last dose of systemic immunosuppressive therapy (eg. calcineurin inhibitors, immunosuppressive antibodies, mycophenolate mofetil, ruxolitinib, ibrutinib) except for prednisone ≤ 10 mg or equivalent.
• Previous treatment with any anti-CD7 directed therapy.
• Known hypersensitivity to one or more of the study agents.
• Active or latent Hepatitis B or active Hepatitis C without previous curative treatment.
• Confirmed HIV infection.
• History of concurrent second cancers requiring active, ongoing systemic treatment with the exception of adjuvant hormonal therapy for breast or prostate cancer.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test at time of enrollment and within 7 days of starting lymphodepleting chemotherapy.
• Serious active infection or another serious underlying medical condition that in the opinion of the treating physician would impair the ability of the patient to receive protocol treatment including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia or serious, unstable neurologic symptoms.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Wugen, Inc.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Lymphoma, T-Cell; Leukemia, Myeloid, Acute; Immunoblastic Lymphadenopathy; Enteropathy-Associated T-Cell Lymphoma; Lymphoma, T-Cell, Peripheral; Lymphoma, Large-Cell, Anaplastic; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Prolymphocytic, T-Cell; Lymphoma, Extranodal NK-T-Cell; Sezary Syndrome

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Hematologic Diseases; Lymphadenopathy; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Prolymphocytic; Leukemia, T-Cell; Lymphoma, T-Cell, Cutaneous

Study Officials

• Geoffrey Uy, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two cohorts (AML and T-NHL) will enroll and be treated independently in the Dose Escalation portion of the study. Patients in each cohort will be treated following an accelerated titration 3+3 design, meaning that one patient will be treated at a dose level with continued escalation until a DLT is observed, at which point a traditional 3+3 design will be triggered in that cohort moving forward. Upon confirmation of the recommended phase 2 dose (RP2D) for either cohort, enrollment to the Dose Expansion portion of the study for that cohort will commence.

Study Record Dates

• First Submitted: May 11, 2022
• First Posted: May 17, 2022
• Study Start: October 10, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)