P1, N=16, Completed, Beijing Boren Hospital | Recruiting --> Completed

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) as consolidation early after CAR T therapy, the patient experienced 12 months of disease-free survival to date. Our results confirmed that allogeneic hematopoietic stem cell transplantation after naturally selected CD7 CAR-T therapy can be a potential treatment for patients with CD7-positive R/R-AML.

P1, N=6, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting | N=54 --> 6

P1, N=30, Recruiting, Zhejiang University

P1, N=15, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

Twelve-month progression-free survival with and without censoring transplantation was 22% (95%CI 4-100) and 57% (41-81), respectively. These results support that autologous CD7 CAR T-cell therapy without T-cell pre-selection is feasible in patients with r/r T-ALL.

P1/2, N=200, Recruiting, The General Hospital of Western Theater Command

T cells regenerating after lymphodepletion lacked CD7 expression, were polyclonal and responded to SARS-CoV-2 vaccination; CD7+ immune cells reemerged concomitantly with CAR T cell disappearance. In conclusion, autologous anti-CD7 PEBL-CAR T cells have powerful antileukemic activity and are potentially an effective option for the treatment of T-ALL.

CD7 is an active and safe target that shows promising results in the treatment of relapsed and/or refractory (r/r) T-cell malignancies.

WU-CART-007 at the RP2D demonstrated a high response rate in patients with relapsed/refractory T-ALL/LBL and has the potential to provide a new treatment option. ClinicalTrials.gov registration: NCT04984356.

P1/2, N=29, Completed, Wugen, Inc. | Active, not recruiting --> Completed | N=44 --> 29 | Trial completion date: Aug 2026 --> Jun 2024 | Trial primary completion date: May 2026 --> Jun 2024

P1/2, N=60, Recruiting, Essen Biotech | Not yet recruiting --> Recruiting

P2, N=125, Not yet recruiting, Wugen, Inc.

In the later four months of follow-up, in the absence of any immunodepression treatment, no signs of GVHD were observed. This case initially demonstrates the potential of CD7 UCAR-T in the prophylaxis of GVHD.

P=N/A, N=50, Completed, Hebei Senlang Biotechnology Inc., Ltd. | Recruiting --> Completed | Trial completion date: Jun 2023 --> Oct 2023

P1/2, N=26, Recruiting, Bambino Gesù Hospital and Research Institute | Not yet recruiting --> Recruiting | Trial completion date: Jun 2040 --> Sep 2040 | Initiation date: Jan 2024 --> Apr 2024 | Trial primary completion date: Jun 2028 --> Sep 2028

P1/2, N=60, Not yet recruiting, Essen Biotech

Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.).

Patients aged ≤14 in the CD7 CAR-T group achieved high 2-year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR-T therapy followed by allo-HSCT is not only effective and safe for r/r T-ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM.

P1/2, N=44, Active, not recruiting, Wugen, Inc.

No abstract available

P1, N=81, Recruiting, Zhejiang University | Phase classification: P1/2 --> P1 | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2022 --> Dec 2023

Most (72%; 13) pts had G1-2 CRS events; a single G3 CRS event was reported which resolved within 72 hours after receiving tocilizumab, steroids, and low-dose vasopressors. WU-CART-007 has demonstrated an acceptable safety profile and preliminary evidence of anti-leukemic activity. This program advances CAR-T cell therapy in heavily pre-treated patients with R/R T-ALL/LBL.

For all the patients who reached complete remission or CRi, CD7+ clearance rates were higher with statistical significance. Our results proved potential indicators for CRS prediction and prognosis.

SENL101 expanded robustly but persisted shortly, which on the other hand, contributed to the recovery of CD7 + T and NK cells, thereby reducing the risk of infection. An expanded cohort is warranted to verify the long-term benefit of SENL101 for T-cell malignant patients.

P1, N=4, Recruiting, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine | Trial completion date: Apr 2024 --> Nov 2024 | Trial primary completion date: Apr 2023 --> Aug 2024

P1/2, N=26, Not yet recruiting, Bambino Gesù Hospital and Research Institute | Trial completion date: Feb 2040 --> Jun 2040 | Initiation date: Oct 2023 --> Jan 2024 | Trial primary completion date: Mar 2028 --> Jun 2028

P1/2, N=44, Active, not recruiting, Wugen, Inc. | Recruiting --> Active, not recruiting

P1, N=9, Recruiting, Hebei Senlang Biotechnology Inc., Ltd.

Cytokine release syndrome occurred in 91.7% of patients (grade 1/2 in 80.0%, grade 3/4 in 11.7%) and 5% of patients had neurotoxicity. NS7CAR-T therapy is effective in treating R/R T-ALL/LBL patients with promising PFS while maintaining a manageable safety profile.

One patient had progression free survival of >3 years. With manageable toxicity profile, GC027 demonstrated superior clinical efficacy to standard chemotherapy regimens in (R/R) T cell malignancies.

Two different LDC regimens have been tested: standard LDC (fludarabine 30 mg/m2/day x 3 days and cyclophosphamide 500 mg/m2/day x 3 days), and enhanced LDC (eLDC; fludarabine 30 mg/m2/day x 4 days and cyclophosphamide 1000 mg/m2/day x 3 days)...Most (72%; 13/18) pts had G1-2 CRS events; a single G3 CRS event was reported which resolved within 72 hours after receiving tocilizumab, dexamethasone, and low-dose vasopressors...This program advances CAR-T cell therapy in heavily pre-treated patients with R/R T-ALL/LBL. Enrollment is ongoing.

We used total body irradiation (TBI)-based conditioning regimens (n=128) or Busulfan/Melphalan-based regimens (n=11). To prevent graft-versus-host disease (GVHD), we used ATG along with a short-term regimen combining methotrexate, cyclosporine/tacrolimus, and mycophenolate mofetil...Conclusions Our parallel study showed that T-ALL/LBL patients, who achieved CR via CD7 CAR-T therapy followed by a consolidation allo-HSCT, had similar favorable OS and LFS compared to patients who underwent allo-HSCT in the CR1 state induced by chemotherapy. This was achieved without increasing the incidence of GVHD, infections, or TA-TMA.

Hence, given the comparable remission rate and remarkable safety, autologous CD7 CAR T-cell therapy would be prioritized for recommendation for r/r T-ALL/LBL patients with low tumor load and access to collect enough normal T cells from their own body for CAR T-cell manufacture. CD5 CAR T-cell therapy is regarded as an option for patients with CD5 positive encountering treatment failure or relapse after CD7 CAR T-cell therapy.

A lymphodepletion regimen was administered to all patients using fludarabine (30 mg/m2 per day) and cyclophosphamide (500 mg/m2 per day) for three consecutive days (day -5 to day -3) before CAR-T infusion. UCD7-CAR T therapy is a safe and highly effective pediatric T-ALL/LBL treatment. More patients and longer follow-ups are needed for validation.

The conditioning regimens utilized were either total body irradiation (TBI)-based (n=9), busulfan-based (n=6), or melphalan-based (n=1). Combining CAR-T therapy with a follow-up second HSCT presents a strategy for these heavily pre-treated patients, offering promising prospects for survival. However, further evaluation of this treatment approach is required, necessitating long-term monitoring and a larger patient cohort.

Myeloablative conditioning regimens with either total body irradiation (TBI)/fludarabine (51, 56.7%) based or busulfan/fludarabine (39, 43.3%) based were applied...Cyclosporine, mycophenolate mofetil and short-term methotrexate were employed for graft-versus-host disease (GVHD) prophylaxis... Our study has demonstrated that CD7 CART followed by allo-HSCT has remarkably improved long-term DFS for chemotherapy-resistant T-ALL/LBL, and achieved comparable results in safety and efficacy with chemotherapy-sensitive disease post-transplant. Our study has also shown the profiles of somatic and germline gene mutations in r/r T-ALL/LBL, and identified some positive and negative impact factors for prognosis after transplant in this setting.

RNA-seq further confirmed an elevation of activated CD4 memory cell subpopulation. However, limited distinction on crucial regulatory genes and pathways was revealed, suggesting the safety and feasibility of UCAR-T application as well as the potential translational rather than transcriptional regulation of CD7 antigen.

P1, N=54, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting

P1/2, N=26, Not yet recruiting, Bambino Gesù Hospital and Research Institute