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JOURNAL ONKOLOGIE – STUDIE
Anti-CD19-ALL

Tafasitamab (MOR00208) in Pediatric Patients With Relapsed or Refractory Acute B Lineage Leukemia

Rekrutierend

NCT-Nummer:
NCT05366218

Studienbeginn:
März 2023

Letztes Update:
27.07.2023

Wirkstoff:
Tafasitamab

Indikation (Clinical Trials):
Leukemia, Leukemia, Lymphoid, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
-

Sponsor:
University Hospital Tuebingen

Collaborator:
-

Studienleiter

Peter Lang, Prof.
Principal Investigator
University Childrens Hospital Tübingen

Kontakt

Studienlocations
(3 von 11)

University childrens Hospital
72076 Tübingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Peter Lang, Prof. Dr.
Phone: 004970712984744
E-Mail: peter.lang@med.uni-tuebingen.de

Michael Abele, Dr.
Phone: 0049707184744
E-Mail: michael.abele@med.uni-tuebingen.de» Ansprechpartner anzeigen
Centrum für Chronische Immundefizienz des Universitätsklinikums Freiburg
Breisacher Str. 115
79106 Freiburg
(Baden-Württemberg)
DeutschlandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Stefan Schönberger, Dr.

Michaela Höfs, Dr.» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed Description:

Acute lymphoblastic leukemia is the most common malignancy in children. In patients with >

2nd relapse or in patients who relapse after previous stem cell transplantation (SCT),

conventional chemotherapy or even subsequent SCT results only in low probabilities for event

free survival (1-year EFS ~30%) with a generally poor prognosis. Major cause of death is a

subsequent relapse. To date there is no standard therapy available. The aim of this study is

to establish an antibody approach as an additional therapy. Therefore, the safety and

efficacy of the anti-CD19-antibody tafasitamab in such pediatric very high-risk patients will

be evaluated. Patients will be included in the following stages of disease: newly emerging or

persistent minimal residual disease (MRD) after a first SCT; SCT without having reached a

sufficient molecular remission prior to transplant (defined as MRD ≥10E-4) irrespective of

MRD after SCT; underwent a second or subsequent SCT irrespective of MRD after SCT.

Tafasitamab will be used as a relapse prophylaxis as well as a treatment for patients with

low detectable low MRD. The treatment is intended to reduce the likelihood of overt relapse

after SCT in a collective of patients at highest risk of relapse, thereby improving the

long-term survival of these patients. The bi-weekly application of anti-CD19-antibody has

already shown promising results in compassionate use settings in pediatric patients.

Furthermore, the safety of tafasitamab has already been analyzed in multiple studies in

adults and has proven to be well tolerable. As a control group published data for these

patient groups will be used with a combined 1-year EFS of 30% in which patients have been

treated at the current standard of care.

The study consists of 2 parts:

The first part will evaluate safety along with the maximum tolerated dose of tafasitamab in

pediatric patients. This will involve intra- and inter-individual dose escalation using

pre-determined dose levels before the dose-finding phase is completed. If dose-limiting drug

side effects occur during this dose-finding phase, additional patients will be included in

the interindividual dose escalation until the maximum tolerated dose of tafasitamab is

defined for the remainder of the study. For this dose-finding phase, a minimum of six and a

maximum of 25 patients will be included.

Immediately thereafter, the second study phase begins, in which all patients from the

dose-finding phase who have not experienced a dose-limiting toxicity, as well as additional

enrolled patients, receive the defined maximum tolerated dose of tafasitamab. In this phase

of the study, in addition to the continued recording of drug side effects, the efficacy of

tafasitamab will be assessed using defined endpoints. A minimum evaluable number of 18

patients is planned for the assessment of these endpoints; to compensate for possible patient

dropout during the study, recruitment of a minimum of 20 patients and a maximum of 39

patients, depending on the course of the dose-finding phase, is planned.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- B-lineage (CD19 positive) ALL (B, pro-B, pre-B or c-ALL)

- Patients must have either

- underwent a first allogeneic stem cell transplantation with newly emerging or

persistent MRD load posttransplant or

- have received stem cell transplantation without having reached a sufficient

molecular remission prior to transplant (defined as MRD ≥10E-4) irrespective of

MRD after SCT or

- underwent a second or subsequent allogeneic stem cell transplantation

irrespective of MRD after SCT

- Females of childbearing potential (FCBP1) must agree

- to utilize two reliable forms of contraception simultaneously or practice

complete abstinence from heterosexual contact for at least 3 months before

starting study drug, while participating in the study (including dose

interruptions), and for at least 3 months after study treatment discontinuation

and must agree to regular pregnancy testing during this timeframe

- to abstain from breastfeeding during study participation and 3 months after study

drug discontinuation.

- Males must agree

- to use a latex condom during any sexual contact with FCBP while participating in

the study and for 3 months following discontinuation from this study, even if he

has undergone a successful vasectomy

- to refrain from donating semen or sperm during study participation and for 3

months after discontinuation from this study treatment.

Exclusion Criteria:

- Frank relapse (>5% leukemic blasts)

- Philadelphia chromosome-positive (Ph+) ALL

- Ejection fraction <25% on echocardiography

- Cystatin C-clearance <40ml/min

- Liver function abnormalities with bilirubin >4 mg/dL and elevation of transaminases

higher than 400 U/L

- Severe infection (HIV, Chronic active viral hepatitis), tests have to be conducted at

screening

- Acute GvHD III-IV or extensive chronic GvHD

- The following immunosuppressive drugs (≥ 1 week of administration): steroids ≥ 1mg/kg

body weight, cytostatics (except intrathecal/intracerebroventricular application for

CNS treatment)

- Application of other experimental therapy modalities in the last 4 weeks

- Significant psychiatric disabilities, uncontrolled seizure disorders or severe

peripheral neuropathy/ leukoencephalopathy

- Signs of autoimmune disease (i.e. idiopathic thrombocytopenic purpura, autoimmune

hemolytic anemia)

- Subjects that do not agree to refrain from donating blood while on study drug

- Concurrent severe or uncontrolled medical disease which by assessment of the treating

physician could compromise participation in the study

- Women during pregnancy and lactation

- History of hypersensitivity to the investigational medicinal product or to any drug

with similar chemical structure or to any excipient present in the pharmaceutical form

of the investigational medicinal product.

Studien-Rationale

Primary outcome:

1. Primary endpoint Part I (Time Frame - 49 days):
Determination of maximum tolerated dose of MOR00208 in pediatric patients

2. Primary endpoint Part II (Time Frame - 545 days):
Time until hematological relapse (> 5% leukemic blasts) or increase of MRD ≥ 2 log in bone marrow during an observation time of 545 days accounting for competing risks

Secondary outcome:

1. Pharmakokinetic of MOR00208 (Time Frame - 8 days):
Mean plasma concentrations of MOR00208 will be calculated and displayed graphically

2. Safety and toxicity of MOR00208 - Part I (Time Frame - 49 days):
Adverse events will be presented in line listings and also in cumulative tabulations

3. Treatment success (Time Frame - 365 days):
Rate of patients with treatment success defined as survival without newly emerging MRD or increasing MRD ≥ 2 log in bone marrow or peripheral blood or unacceptable toxicity

4. Overall survival (Time Frame - 545 days):
OS from date of first dose until end of follow up at 545 days will be analyzed using Kaplan-Meier-Methods, presenting corresponding statistical parameters and 95% confidence limits and Kaplan-Meier survival curves. Patients alive at 545 days and patients that could not be followed up until 545 days but were seen alive at the last visit will be censored.

5. MRD reduction (Time Frame - 545 days):
The amount of patients with reduction of at least 1 log at any time point compared to baseline MRD measurement between SCT and start of study treatment will be calculated and displayed graphically. Rates and 95%-confidence limits are also provided.

6. B cell numbers (Time Frame - 545 days):
Mean B cell numbers will be calculated and displayed graphically with 95%-confidence limits.

7. Cytotoxic lysis (Time Frame - 545 days):
Cytotoxic lysis will be calculated and displayed graphically.

8. Safety and toxicity of MOR00208 - Part II (Time Frame - 545 days):
Adverse events will be presented in line listings and also in cumulative tabulations

Geprüfte Regime

  • Tafasitamab (MOR00208):
    Antibody vaccination

Quelle: ClinicalTrials.gov


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