University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Location status: Recruiting
NCT Number: NCT07451054
This is a phase 1, open-label, dose-finding study to assess the safety, feasibility, pharmacokinetics and preliminary efficacy of autologous base edited anti-CD45 CAR T cells (referred to as "CART-45 cells") following an autologous transplant of CD45 base edited hematopoietic stem and progenitor cells (referred to as "CD45BE-HSPC") in patients with relapsed or refractory hematologic malignancies.
Interested in participating?
Request Info18 year and older
All sexes
Interventional
Phase 1
Philadelphia, Pennsylvania, 19104, United States
Location status: Recruiting
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
a. B-cell Non-Hodgkin Lymphoma (B-cell NHL)- including the following sub-types:
i. Patients with any of the following large B-cell lymphoma diagnoses who meet the prior treatment criteria outlined below: Diffuse Large B-cell Lymphoma not otherwise specified (DLBCL NOS); Primary Cutaneous DLBCL; Primary Mediastinal (thymic) Large B-cell Lymphoma; ALK+ Anaplastic Large B-cell Lymphoma; High-Grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 rearrangements (i.e., "Double or Triple Hit"); High-grade B-cell Lymphoma, NOS; T-cell Rich B-cell Lymphoma; Transformed Follicular Lymphoma; or any aggressive B-cell lymphoma arising from indolent lymphoma.
ii. Follicular Lymphoma
iii. Mantle Cell Lymphoma
iv. Marginal Zone Lymphoma- relapsed/refractory disease after at least 2 prior lines of appropriate therapy, including a Bruton tyrosine kinase (TKI) inhibitor. Note: Single-agent monoclonal antibody therapy does not count towards prior lines of therapy.
b. T-cell Non-Hodgkin Lymphoma (T-cell NHL)
i. Histologically or cytologically confirmed relapsed or refractory (r/r) mature aggressive T- and NK-cell neoplasms as defined in the 5th edition of the WHO Classification of Hematolymphoid tumors, which includes any of the following diagnoses:
ii. Must have received at least one prior line of systemic therapy for their lymphoma. Additional prior treatment provisions required for the following indications:
c. Hodgkin Lymphoma (HL)
i. Patients with histologically proven classical Hodgkin Lymphoma that is CD45 positive by IHC or flow cytometry by a CLIA certified laboratory; AND
ii. Relapsed/refractory disease after at least 2 prior lines of therapy which must include the following:
a. Have no active GVHD and require no immunosuppression
b. Are more than 6 months from transplant at the time of physician-investigator confirmation of eligibility
Exclusion criteria
Autologous base edited anti-CD45 CAR T cells
CD45 base edited hematopoietic stem and progenitor cells
Time frame: Up to 15 years post infusion
Type, frequency and severity of adverse events as assessed by CTCAE V6.0. Each disease-specific cohort will be analyzed separately.
Time frame: 28 days post-CART-45 infusion
Unacceptable toxicity as defined by the protocol. DLTs will be evaluated separately by each disease-specific cohort.
Time frame: 28 days post-CART-45 infusion
Selected based on an isotonic regression model. The MTD will be established separately by disease-specific cohort
Time frame: 3 months post-CART-45 infusion
Evaluated by Cohort/dose level using a multi-criteria decision analysis.
Time frame: 3 months
Calculated based on the proportion of subjects with CD45BE-HSPC products that fail to meet the product release criteria, out of the number of subjects in whom manufacturing was attempted.
Time frame: 3 months
Calculated based on the proportion of subjects with CART-45 products that fail to meet the product release criteria, out of the number of subjects in whom manufacturing was attempted.
Time frame: 3 months
Calculated based on the proportion of subjects with CD45BE-HSPC products that fail to meet the assigned dose, out of the number of subjects in whom manufacturing was attempted.
Time frame: 3 months
Calculated based on the proportion of subjects with CART-45 products that fail to meet the assigned dose, out of the number of subjects in whom manufacturing was attempted.
Time frame: 3 months
Proportion of eligible patients who receive both investigational products as planned; by individual disease-specific cohort and in aggregate.
Time frame: 28 days after treatment
Number of subjects with engraftment of CD45BE-HSPC.
Time frame: Up to 15 years after last CART-45 Cells administration
Duration of time from CD45BE-HSPC infusion (Day 0) to the date of death, for any reason
Time frame: Up to 12 months following CART-45 administration
Proportion of subjects with CR or PR at Month 3 as compared to baseline.
Time frame: Up to 12 months following CART-45 administration
Proportion of subjects with a best objective disease response of CR or PR recorded between Month 3 and the end of primary follow-up (Month 12); or start of new anticancer therapy, whichever comes first.
Time frame: Up to 12 months following CART-45 administration
Time from the date when the response criteria of CR or PR is first met (at or following Month 3), to the date of confirmed disease progression, death, or other censoring event as described below.
Time frame: Up to 15 years after product administration
The duration of time from the CD45BE-HSPC transplant (Day 0) to the date of confirmed disease progression or death, whichever occurs first. Otherwise, PFS will be censored at the date of the last response assessment, date of new anti-cancer treatment is initiated (including CART-45 retreatment) or the data cut-off date; whichever occurs first.
Contact information is provided by the study sponsor or research team.
University of Pennsylvania
Other
Phase 1 Study of Autologous Anti-CD45 CAR T Cells in Combination With CD45 Base Edited HSPCs in Patients With Relapsed or Refractory Hematologic Malignancies
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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