UMCG HO161 NHL

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Main info

Identifier:
HOVON 161 CART / NHL
Sponsor:
UMCG
Working group party:
Lymphoma
Age:
>= 18
Stage:
3rd Line
Echelon:
Level A
Included patients:
52
(of 300)
Active sites:
7
(of 7)
Title:

A phase II non-inferiority study comparing point-of-care produced CAR T-cell to commercial CAR T-cells in patients with relapsed/refractory Non-Hodgkin Lymphoma

Timeline

Scheduled
Actual
2020
02 Oct
Opportunity
2020
15 Dec
Development
2021
18 Jan
Development
2021
18 Aug
Submission in Progress
2022
15 Jul
EC Approval
2022
25 Aug
EC Approval
2022
15 Sep
Activated
2022
13 Oct
Submission in Progress
2022
14 Oct
Activated
2022
14 Oct
First Site
2022
15 Oct
First Site
2022
18 Oct
FPI
2022
30 Oct
FPI
2025
15 Oct
ClosedForInclusionScheduledStart
2027
15 Oct
CloseoutInProgressLastPtOutScheduledStart
2027
30 Oct
Endpoint Analysis
2028
15 Oct
Archived
2058
14 Oct
Destruction

News

25OCT2023: Substantial Amendment 2 is implemented

20JAN2023: Substantial Amendment 1 is implemented

18OCT2022: First study patient is included

14OCT2022: Study is open and first site is activated

06OCT2022: Investigator File (IF) uploaded
All sites have received by email a link to the IF that contains all documents required to receive local approval. This IF contains documents like: Protocol, ICF, ABR form, cEC (CCMO) approval, CA approval, eCRF instructions, Lab manual, etc.

Details

Phase:
Prospective randomized Phase II study
Monitoring Type:
Study Specific
Objectives:

Primary study objective

  • To compare progression free survival (PFS) of patients randomized to investigational point-of-care (PoC) ARI-0001 CAR T-cells versus PFS of patients randomized to commercial standard-of-care (SoC) (axicabtagene ciloleucel (Axi-cel, Yescarta)) CAR T-cells in patients with R/R DLBCL.

Secondary study objectives

  • To evaluate response rates (ORR and CR).
  • To evaluate safety and toxicity of ARI-0001 and Axi-cel.
  • To assess overall survival (OS).
  • To evaluate quality of life (QoL).
  • To assess costs associated with both treatment regimens (ARI-0001 vs Axi-cel).
  • To evaluate CAR T-cell expansion, persistence, and T-cell characteristics in both treatment arms (ARI-0001 vs Axi-cel).
  • To evaluate PoC CAR T-cell production characteristics (e.g. number of viable T-cells, transduction efficiency, T-cell subsets (activated T-cells, memory T-cells)), including the functional characteristics (e.g. potency tests) between the different production sites.
  • To evaluate the association of the functional characteristics (e.g. potency tests) of the CAR T-cell products (ARI-0001 CAR T-cells) with CAR T-cell expansion, persistence, adverse events, response rates and progression free survival.
  • To assess the proportion of successful batches between the different production sites.
  • To evaluate the number of days between leukapheresis and infusion of CAR T-cells (vein-to-vein time).

Eligibility

Inclusion Criteria:
  • Histologically confirmed DLBCL and associated subtypes, defined by WHO 2016 classification: DLBCL not otherwise specified (NOS), High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (DHL/THL) and FL3B, T-cell/histocyte rich B-cell lymphoma, Primary mediastinal B-cell lymphoma, transformed lymphoma (transformed follicular) and R/R after at least 2 lines of systemic therapy
  • Age ≥ 18
  • Eastern Cooperative Oncology Group (ECOG)/WHO performance status 0-2 (appendix D)
  • If the patient has a history of central nervous system (CNS) involvement, then he/she must have
    • No signs or symptoms of CNS involvement
    • No active disease on magnetic resonance imaging (MRI)
    • Absence of large cell lymphoma in cerebral spinal fluid (CSF) on cytospin preparation or flow cytometry, regardless of the number of white blood cells
  • Estimated life expectancy of >3 months other than primary disease
  • Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen
  • Signed and dated informed consent before conduct of any trial-specific procedure
  • Patient is capable of giving informed consent
Exclusion Criteria:
  • Absolute neutrophil count (ANC) <1.0x109/L
  • Platelet count <50x109/L
  • Absolute lymphocyte count <0.1x109/L
  • Primary CNS lymphoma
  • Known history of infection with hepatitis C or B virus unless treated and confirmed to be polymerase chain reaction (PCR) negative
  • Active HIV infection with detectable viral load or CD4 T-cell count below 0.20x10^9/L
  • Known history or presence of seizure activities or on active anti- seizure medications within the previous 12 months
  • Known history of CVA within prior 12 months
  • Unstable neurological deficits
  • Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic or inflammatory disease
  • Active systemic autoimmune disease for which immunnosupressive therapy is required
  • Presence of CNS disease that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity, baseline dementia that would interfere with therapy or monitoring, determined using mini-mental status exam at baseline
  • Active systemic fungal, viral or bacterial infection
  • Clinical heart failure with New York Heart Association class ≥2 (appendix F) or Left Ventricular Ejection Fraction (LVEF) <40%
  • Resting oxygen saturation <92% on room air
  • Liver dysfunction as indicated by total bilirubin, AST and/or ALT >5 x institutional ULN, unless directly attributable to the lymphoma or Gilbert disease
  • GFR <40 mL/min calculated according to the modified formula of Cockcroft and Gault or by direct urine collection
  • Pregnant or breast-feeding woman
  • Active other malignancy requiring treatment
  • Medical condition requiring prolonged use of systemic immunosuppressives with exception of prednisolone <10 mg/day
  • History of severe immediate hypersensitivity reaction against any drug or its Ingredients/ impurities that is scheduled to be given during trial participation e.g. as part of the mandatory lymphodepletion protocol, premedication for infusion, or rescue medication/salvage therapies for treatment related toxicities
  • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Registration Details

Patients who are possibly eligible for this trial should first be discussed at the National Tumor Board. If patient seems eligible and has provided a written informed consent, the patient should be registered on the UMCG platform to reserve a slot. Thereafter, patients should be randomized via HOVON's eCRF database ALEA by one of the following options:

  • By ALEA; Use goto eCRF button > select the [Patient tab] and click the [Add new patient] button. Complete all items and click the [Submit] button
  • By mailing the completed registration/randomization CRF to hdc@erasmusmc.nl
  • By phone +31 (0)10 704 1560 Monday through Friday, from 09:00 to 17:00 CET

Participating Sites

Ziekenhuizen die deelnemen aan het onderzoek staan benoemd op de HOVON website bij het onderzoek. Het kan zijn dat uw ziekenhuis niet genoemd wordt, maar wel aan het onderzoek deelneemt. Informeer hiernaar bij uw arts.

Site
7 results
Order by
Accrual rate
Activation date
NL-Groningen-UMCG
23
14 Oct 2022
NL-Amsterdam-AMC
10
25 Apr 2023
NL-Maastricht-MUMC
9
21 Jun 2023
NL-Rotterdam-ERASMUSMC
4
13 Sep 2023
NL-Nijmegen-RADBOUDUMC
4
28 Mar 2023
NL-Leiden-LUMC
1
30 Dec 2023
NL-Utrecht-UMCUTRECHT
1
17 Nov 2023
= Active hospitals
= Inactive hospitals

Participating Parties

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