Clinical trial NCT04526834: Phase 1 Study of Autologous CD30.CAR-T in Relapsed or Refractory CD30 Positive Non-Hodgkin Lymphoma
Official title: Phase 1 Study of CD30-Directed Genetically Modified Autologous T-Cells (CD30.CAR-T) in Patients With Relapsed or Refractory CD30 Positive Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Anaplastic Large Cell Lymphoma
Peripheral T Cell Lymphoma
Extranodal NK/T-cell Lymphoma
Diffuse Large B Cell Lymphoma
Primary Mediastinal Large B-Cell Lymphoma (PMBCL)
Keywords: CD30, r/r NHL, DLBCL, ALCL, ENKTCL, PMBCL, PTCL, adult
Lead sponsor: Tessa Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-08-26
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase 1 study to evaluate safety and dose-limiting toxicity of autologous CD30.CAR-T in subjects with relapsed or refractory CD30+ Non-Hodgkin Lymphoma

Detailed description: Adult patients with relapsed or refractory CD30-positive Non-Hodgkin Lymphoma who have failed standard available therapies and who meet eligibility criteria will have blood drawn to manufacture the CD30.CAR-T cells.

CD30.CAR-T cells will be infused once following the completion of lymphodepleting chemotherapy with Bendamustine and Fludarabine.

Subjects will be closely monitored for DLT and safety.

Eligibility criteria: Inclusion Criteria:

Eligibility is determined priori to leukapheresis. Patients must satisfy the following criteria to be enrolled in this study:

1. Signed Informed Consent Form
2. Male or female patients who are 18-75 years of age
3. Histologically confirmed ALCL, PTCL- NOS, ENKTCL nasal type, DLBCL-NOS and PMBCL
4. Relapsed or refractory CD30-positive NHL who have failed all available standards of therapy. Patients may or may not have received an autologous or allogeneic HSCT CD30-positive tumor
5. At least 1 measurable lesion according to the Lugano Classification
6. ECOG PS of 0 to 1 or equivalent Karnofsky PS Anticipated life expectancy \>12 weeks

Exclusion Criteria:

1. CNS involvement by malignancy
2. Inadequate laboratory abnormalities at screening:

   Hgb ≤ 8.0 g/dL Total bilirubin \> 1.5 x ULN (\>2 x ULN for patients with Gilbert's syndrome) AST and ALT ≥ 5 x ULN CrCL ≤ 45 mL/min (as measured by Cockcroft-Gault equation) ANC ≤ 1000/uL Platelets ≤75,000/uL PR or INR \>1.5 x ULN aPTT\> 1.5 x ULN
3. Active uncontrolled bleeding or a known bleeding diathesis
4. Inadequate pulmonary function defined as pulse oximetry \< 90% on room air
5. Ongoing treatment with immunosuppressive drugs including calcineurin inhibitions, TNFalpha, mTOR, etc or chronic systemic corticosteroids (\>10 mg/day prednisone or equivalent for \>48 hours)
6. Received prior therapy of:

   Anti-CD30 Ab based therapy within the previous 8 weeks Previous CD30.CAR-T investigational product Bi-specific CD30 Ab within the previous 8 weeks Allogenic HSCT in the last 180 days Autologous HSCT within 90 days
7. Active GVHD requiring immune suppression regardless of grade
8. HIV positive
9. Active HBV and/or HCV

Primary outcomes:
measure: To evaluate safety and dose limiting toxicities (DLT) of autologous CD30.CAR-T and establish the recommended Phase dose
timeFrame: Day 0 to 28 for DLT
Secondary outcomes:
measure: To evaluate pharmacokinetics of autologous CD30.CAR-T
timeFrame: Start of infusion of CD30.CAR-T (Day 0) until year 5
measure: Objective Response Rate (ORR)
timeFrame: Start of CD30.CAR-T (Day 0) until progressive disease or start of new cancer therapy, whichever comes first, up to one year
measure: Duration of Response (DOR)
timeFrame: Start of CD30.CAR-T (day 0) until progressive disease or death, whichever comes first, up to one year
measure: Progression Free Survival (PFS)
timeFrame: Start of CD30.CAR-T (Day 0) until progressive disease or death, whichever comes first, up to one year
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Centre
state: Texas
Study officials:
affiliation: MD Anderson
name: Sairah Ahmed
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.