Treatment of patients with relapsed or refractory CD19+ lymphoid disease with T lymphocytes transduced by RV-SFG.CD19.CD28.4-BBzeta retroviral vector – A unicenter Phase I/II clinical trial [HD-CAR-1]

2024-516832-82-00 Phase I and Phase II (Integrated) - Other Ongoing, recruiting

Start 27 Aug 2018 · Status Ongoing, recruiting · 1 EU/EEA countries · 2 sites

Overview

Sponsor-declared trial summary

Phase Phase I and Phase II (Integrated) - Other
Status Ongoing, recruiting
Participants planned 63
Countries 1
Sites 2

Accute lymphoblastic leukemia recurrent, Non-Hodgkin´s lymphoma NOS refractory

The main purpose of the study is to evaluate the safety and feasibility of escalating doses of autologous activated peripheral blood T lymphocytes (ATLs) genetically modified to express third-generation CARs (comprising the CD28 and CD137 (4-1BB) costimulatory domain) that target the CD19 molecule in patients with refr…

Key facts

Sponsor
Universitaetsklinikum Heidelberg AöR
Participant type
Pediatric, Patients
Age range
0-17 years, 18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Hemic and Lymphatic Diseases [C15]
Trial duration
27 Aug 2018 → ongoing
Decision date (initial)
2024-09-19
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2024-516832-82-00
EudraCT number
2016-004808-60
ClinicalTrials.gov
NCT03676504

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Therapy, Efficacy

The main purpose of the study is to evaluate the safety and feasibility of escalating doses of autologous activated peripheral blood T lymphocytes (ATLs) genetically modified to express third-generation CARs (comprising the CD28 and CD137 (4-1BB) costimulatory domain) that target the CD19 molecule in patients with refractory or relapsed CD19+ lymphoid disease such as ALL or NHL including CLL, DLBCL, FL and/or MCL.

Secondary objectives 10

  1. Evaluation of survival and function of chimeric antigen receptor (CAR) TCs directed against CD19 (CD19.CAR TC) in vivo
  2. Characterization of in vivo cellular pharmakokinetics
  3. Correlation of clinical response and number of circulating gene modified cells
  4. Reduction of disease burden with CD19.CAR TC transfusions
  5. Anti-tumor efficacy of CD19.CAR TCs in patients with CD19+ lymphoid disease (overall response rate (ORR), complete response (CR), partial response (PR)) at day 90 (EOS) after CD19.CAR TC transfusion)
  6. Time to response (at least PR) after the CD19.CAR TC transfusion
  7. Duration of overall response (DOR) after the CD19.CAR TC transfusion
  8. Progression-free survival (PFS) after the CD19.CAR TC transfusion
  9. Overall survival (OS) after the CD19.CAR TC transfusion
  10. Correlation of B-cell depletion in vivo and response to CD19.CAR TC treatment

Conditions and MedDRA coding

Accute lymphoblastic leukemia recurrent, Non-Hodgkin´s lymphoma NOS refractory

VersionLevelCodeTermSystem organ class
21.0 LLT 10063625 Acute lymphoblastic leukemia recurrent 10029104
23.0 LLT 10029595 Non-Hodgkin's lymphoma NOS refractory 10029104

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

  1. Stratum 1-2 (Adults): Confirmed CD19+ ALL, CLL, DLBCL, FL or MCL in patients ≥ 18 years
  2. Stratum 1-2 (Adults): Relapsed or refractory disease (including “molecular relapse” with minimal residual disease (MRD)
  3. Stratum 1-2 (Adults): Renal function defined as: serum creatinine of ≤ 2 x ULN or eGFR ≥ 30 mL/min/1.73 m²
  4. Stratum 1-2 (Adults): Absolute lymphocyte count (ALC) ≥ 100/mm³
  5. Stratum 3: Age of > 3 years until < 18 years at the time of screening
  6. Stratum 3: CD19+ ALL (Ph+ and Ph-) confirmed by cytology and flow cytometry (FACS) AND Relapsed or refractory disease
  7. Stratum 3: Measurable disease/MRD at time of enrollment
  8. Stratum 3: Life expectancy ≥ 12 weeks
  9. Stratum 3: ECOG performance status ≤ 2 (age ≥ 16 years) or Lansky performance status ≥ 50 (age < 16 years) at the time of screening
  10. Stratum 3: Renal function defined as serum creatinine-clearance ≥ 30 mL/min/1.73 m²
  11. Stratum 3: Absolute lymphocyte count (ALC) ≥ 100/mm³

Exclusion criteria 10

  1. Stratum 1-2 (Adults): Immunosuppressive medication with the exception of ≤ 30 mg prednisolone/d or equivalent at the time of CAR TC transfusion
  2. Stratum 1-2 (Adults): Any donor lymphocyte infusions (DLI) must be completed > 6 weeks prior to CD19.CAR TC transfusion
  3. Stratum 1-2 (Adults): Florid/acute or chronic Graft-versus-Host disease (GvHD)
  4. Stratum 1-2 (Adults): Uncontrolled acute life-threatening bacterial, viral or fungal infection
  5. Stratum 1-2 (Adults): A primary malignancy which is in complete remission for ≥ 5 years
  6. Stratum 1-2 (Adults): Pregnant or nursing (lactating) women
  7. Stratum 3: immunosuppressive medication with the exception of < 0.5 mg/d*kg BW prednisolone-equivalent at the time of CD19.CAR TC transfusion
  8. Stratum 3: Any donor lymphocyte infusions (DLI) must be completed > 6 weeks prior to CD19.CAR TC transfusion
  9. Stratum 3: Florid/acute or chronic Graft-versus-Host disease (GvHD)
  10. Stratum 3: Uncontrolled acute life-threatening bacterial, viral or fungal infection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

  1. Assessment of toxicities according to the CTCAEv5.0
  2. Assessment of frequency and grade of CRS and/or ICANS
  3. Assessment of dose-limiting toxicity (DLT) and maximum tolerated dose (MTD)
  4. Yield of sufficient NCs by leukapheresis
  5. Successful transduction (>15%) of CD3+ TCs
  6. Yield of the respective dose of transduced TCs (1 to 20x106 transduced CD3+TCs/m2) in the first three dose levels (I-III)
  7. Yield of the respective dose of transduced TCs (5 to 20x107 transduced CD3+ TCs/m2) in the second three dose levels (IV-VI)

Secondary endpoints 10

  1. Evaluation of survival and function of chimeric antigen receptor (CAR) TCs directed against CD19 (CD19.CAR TC) in vivo
  2. Characterization of in vivo cellular pharmakokinetics
  3. Correlation of clinical response and number of circulating gene modified cells
  4. Reduction of disease burden with CD19.CAR TC transfusions
  5. Anti-tumor efficacy of CD19.CAR TCs in patients with CD19+ lymphoid disease (overall response rate (ORR), complete response (CR), partial response (PR)) at day 90 (EOS) after CD19.CAR TC transfusion)
  6. Time to response (at least PR) after the CD19.CAR TC transfusion
  7. Duration of overall response (DOR) after the CD19.CAR TC transfusion
  8. Progression-free survival (PFS) after the CD19.CAR TC transfusion
  9. Overall survival (OS) after the CD19.CAR TC transfusion
  10. Correlation of B-cell depletion in vivo and response to CD19.CAR TC treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

CD19.CAR T cells

PRD11531000 · Product

Active substance
T Lymphocytes Transduced with a RV-SFGCD19CD284-1BBZETA Retroviral Vector
Substance synonyms
HD-CAR-1
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Authorisation status
Not Authorised
MA holder
UNIVERSITY OF HEIDELBERG, MEDICAL FACULTY REPRESENTED BY HEIDELBERG UNIVERSITY HOSPITAL
Paediatric formulation
No
Orphan designation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Heidelberg AöR

23 Total trials 14 Recruiting 7 Ended
Academic / Non-commercial
Sponsor organisation
Universitaetsklinikum Heidelberg AöR
Address
Im Neuenheimer Feld 672, Neuenheim Neuenheim
City
Heidelberg
Postcode
69120
Country
Germany

Scientific contact point

Organisation
Universitaetsklinikum Heidelberg AöR
Contact name
Prof. Dr. Michael Schmitt

Public contact point

Organisation
Universitaetsklinikum Heidelberg AöR
Contact name
Prof. Dr. Michael Schmitt

Locations

1 EU/EEA country · 2 investigational sites

By country

CountryMS statusPlanned subjectsSites
Germany Ongoing, recruiting 63 2
Rest of world — 0 —

Investigational sites

Germany

2 sites · Ongoing, recruiting
Universitaetsklinikum Heidelberg AöR
Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Im Neuenheimer Feld 430, Neuenheim, Heidelberg
Universitaetsklinikum Heidelberg AöR
Department (V) for Internal Medicine, Im Neuenheimer Feld 410, Neuenheim, Heidelberg

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Germany 2018-08-27 2018-09-07

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_HD-CAR-1_public 4
Recruitment arrangements (for publication) placeholder document_minimum dossier 1
Subject information and informed consent form (for publication) L1 1 Erwachsene Pat-info-einwil_DSGVO_public 3
Subject information and informed consent form (for publication) L1 2 Erwachsene Aufkl Einwil Biobank_DSGVO_public 3
Subject information and informed consent form (for publication) L1 3 Eltern Pat-info-einwil_DSGVO_public 4
Subject information and informed consent form (for publication) L1 4 Eltern Aufkl Einwil Biobank_DSGVO_public 3
Subject information and informed consent form (for publication) L1 5 Jugendliche Pat-info-einwil_DSGVO_public 3
Subject information and informed consent form (for publication) L1 6 Jugendliche Aufkl Einwil Biobank_DSGVO_public 3
Subject information and informed consent form (for publication) L1 7 Kinder Pat-info_public 1.2

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-09-04 Germany Acceptable
2024-09-17
 2024-09-19