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| Name | Class |
|---|---|
| Kite, A Gilead Company | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A: B-cell Non-Hodgkin Lymphoma (B-cell NHL), Richter's Transformation (RT) | Experimental |
| |
| Cohort B: T-cell Non-Hodgkin Lymphoma (T-cell NHL), Hodgkin Lymphoma (HL) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CART-45 cells | Biological | Autologous base edited anti-CD45 CAR T cells |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Adverse Events as assessed by CTCAE v6.0 | Type, frequency and severity of adverse events as assessed by CTCAE V6.0. Each disease-specific cohort will be analyzed separately. | Up to 15 years post infusion |
| Occurrence of dose-limiting toxicities (DLTs) | Unacceptable toxicity as defined by the protocol. DLTs will be evaluated separately by each disease-specific cohort. | 28 days post-CART-45 infusion |
| Identification of the maximum tolerated dose (MTD) | Selected based on an isotonic regression model. The MTD will be established separately by disease-specific cohort | 28 days post-CART-45 infusion |
| Identification of a recommended dose for expansion (RDE) | Evaluated by Cohort/dose level using a multi-criteria decision analysis. | 3 months post-CART-45 infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of CD45BE-HSPC products that fail to meet the product release criteria | 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. | 3 months |
| Proportion of CART-45 products that fail to meet the product release criteria |
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Inclusion Criteria:
1. Signed informed consent form 2. Male or females age ≥ 18 years 3. Disease-Specific 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.
1. Patients must have either failed/relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND 2. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy.
ii. Follicular Lymphoma
iii. Mantle Cell Lymphoma
Patients must have either failed/relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND
Relapsed/refractory disease after at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (TKI) inhibitor. Single-agent monoclonal antibody therapy does not count towards prior lines of therapy.
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:
• Peripheral T-cell Lymphoma, NOS (PTCL-NOS);
• Nodal T-cell Lymphomas with T Follicular Helper [TFH] Phenotype, including Follicular T cell Lymphoma, Angioimmunoblastic Lymphoma, or Anaplastic Large Cell Lymphoma (ALCL);
• ALK+ or ALK-, Enteropathy-Associated T-cell Lymphoma (EATL);
• Monomorphic Epitheliotropic Intestinal T-cell Lymphoma (MEITL);
• Extranodal NK/T-cell Lymphoma;
• Primary Cutaneous T-cell Lymphoma (CTCL);
• Transformed Mycosis Fungoides (tMF) without blood involvement;
• Primary Cutaneous Aggressive Epidermotropic CD8+ Cytotoxic T-Cell Lymphoma;
• Subcutaneous Panniculitis-like T-cell Lymphoma.
ii. Must have received at least one prior line of systemic therapy for their lymphoma. Additional prior treatment provisions required for the following indications:
1. Participants with Anaplastic Large Cell Lymphoma (ALCL) must have received prior Brentuximab vedotin, unless contraindicated.
2. Participants with Subcutaneous Panniculitis-like T-cell Lymphoma or Transformed Mycosis Fungoides (tMF) must have received at least 2 prior lines of systemic therapy.
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:
4. Patients are appropriate candidates for autologous HSCT as per physician-investigator clinical discretion
5. Patients with relapsed disease after prior allogeneic SCT must meet the following criteria:
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
6. Adequate organ function defined as:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Abramson Cancer Center Clinical Trials Service | Contact | 215-349-8245 | PMCancerResearch@Pennmedicine.upenn.edu |
| Name | Affiliation | Role |
|---|---|---|
| Noelle Frey, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
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| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| D016399 | Lymphoma, T-Cell |
| D006689 | Hodgkin Disease |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| CD45BE-HSPC | Biological | CD45 base edited hematopoietic stem and progenitor cells |
|
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. |
| 3 months |
| Proportion of CD45BE-HSPC products that fail to meet the protocol-defined dose | 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. | 3 months |
| Proportion of CART-45 products that fail to meet the assigned dose. | 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. | 3 months |
| Evaluate study feasibility | Proportion of eligible patients who receive both investigational products as planned; by individual disease-specific cohort and in aggregate. | 3 months |
| Engraftment of CD45BE-HSPC | Number of subjects with engraftment of CD45BE-HSPC. | 28 days after treatment |
| Overall survival (OS) | Duration of time from CD45BE-HSPC infusion (Day 0) to the date of death, for any reason | Up to 15 years after last CART-45 Cells administration |
| Overall Response/Remission Rate (ORR) | Proportion of subjects with CR or PR at Month 3 as compared to baseline. | Up to 12 months following CART-45 administration |
| Best Overall Response (BOR) | 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. | Up to 12 months following CART-45 administration |
| Duration of Response (DOR) | 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. | Up to 12 months following CART-45 administration |
| Progression-Free Survival (PFS) | 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. | Up to 15 years after product administration |
| D008232 |
| Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |