Optimization of therapy in adult patients with newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma by individualised, targeted and intensified treatment

• Register: EUCTR
• Last refreshed on: 12 March 2024
• Main ID: EUCTR2013-003466-13-DE
• Date of registration: 05/05/2015
• Prospective Registration: Yes
• Primary sponsor: Goethe University Frankfurt
• Public title: Optimization of therapy in adult patients with newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma by individualised, targeted and intensified treatment
• Scientific title: Treatment optimization in adult patients with newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma by individualised, targeted and intensified treatment - a phase IV-trial with a phase III-part to evaluate safety and efficacy of nelarabine in T-ALL patients - GMALL 08/2013
• Date of first enrolment: 15/09/2015
• Target sample size: 900
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003466-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: standard therapy Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): yes

Countries of recruitment

Germany

Contacts

• Name: GMALL Studienzentrale
• Affiliation: University Hospital Frankfurt

• Name: GMALL Studienzentrale
• Affiliation: University Hospital Frankfurt

Key inclusion & exclusion criteria

Inclusion criteria:
• Acute lymphoblastic leukemia (all subtypes except burkitt leukemia, blasts in BM = 25%
or
• Lymphoblastic lymphoma (B- or T-lineage), blasts in BM <25%

• Age: = 18 - = 55 years

• Written Informed consent to participate in the study and the GMALL registry

• Women of childbearing potential (WOCBP) and male sexual partners of WOCBP must be willing to use an effective method of contraception (Pearl-Index < 1%) during the study and at least 6 months thereafter

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 900
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Serious complications (leukemia associated) or concomitant diseases, such as
- severe uncontrollable complications (leukemia associated), i.e. sepsis, pneumonia with hypoxia, shock, bleeding at diagnosis
- renal insufficiency, if not caused by leukemia
- severe impairment of heart or liver function (if not caused by leukemic infiltration)
- severe obstructive or restrictive pulmonary disease
- known HIV infection or other uncontrolled infections
- any other condition that compromises the patient’s eligibility for intensive treatment as described by the study protocol

• Late relapse of childhood leukemia or concurrent malignancy

• Previous cytostatic treatment
- ALL directed (exceptions: standard prephase, application of steroids = 7 days, once-only application of vincristine, cyclophosphamide or other substances as emergency medical intervention)
- directed to other malignancies within the last 10 years before diagnosis of ALL

• Pregnancy or breastfeeding

• Severe psychiatric disease or any severe concomitant condition under which the patient's understanding of importance and consequences of study participation and/or compliance and therapy according to study protocol cannot be expected

• At diagnosis: participation in another trial that interferes with the antileukemic treatment
(exceptions: trials aiming at supportive care, defined accompanying GMALL trials, and at a later timepoint trials with experimental substances, i. e. in case of molecular treatment failure)



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma Age 18 to 55 y
MedDRA version: 21.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0 Level: LLT Classification code 10065923 Term: Lymphoblastic lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Trade Name: Atriance
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: NELARABINE
CAS Number: 121032-29-9
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Pharmaceutical Form:
INN or Proposed INN: PEGASPARGASE
CAS Number: 130167-69-0
Concentration unit: IU international unit(s)
Concentration type: up to
Concentration number: 3750-

Primary Outcome(s)

Primary end point(s): Event free survival compared with GMALL 07/2003

Main Objective: To improve event free survival (EFS), remission duration (RD), disease free survival (DFS) and overall survival (OS) compared with the previous trial GMALL 07/2003

Secondary Objective: 1. To evaluate the role of CNS radiation and the role of chemotherapy alone in high risk ALL in molecular remission by randomised evaluation
R1: CNS rad + i.th. vs i.th.alone
R2: SCT vs chemotherapy in pts with molCR
2. To evaluate the feasibility of the entire treatment concept (i.e. adherence to schedule, administration of single and combination chemotherapy, maintenance therapy)
3. To evaluate feasibility and tolerability of nelarabine (IMP) as part of consolidation treatment in T-ALL
4. To perform prospective and concomitant monitoring of comorbidities and specifically defined serious adverse events
5. To evaluate an innovative overall approach to optimize treatment of a rare, biologically diverse disease by use of subgroup specific targeted and experimental substances within the main trial and in associated studies
6. To set up an interlinked biomaterial bank to prospectively evaluate molecular genetic risk factors and carry out scientific accompanying projects

Timepoint(s) of evaluation of this end point: at 5 years

Secondary Outcome(s)

Secondary end point(s): 1. time (days) until start of consolidation cycle I (for randomisation I)

2. disease free survival (for randomisation II)

Timepoint(s) of evaluation of this end point: 1. Start date of consolidation cycle I

2. at 3,5 years

Secondary ID(s)

GMALL082013

Source(s) of Monetary Support

Novartis Pharma GmbH

Deutsche Krebshilfe e.V.

Ethics review

Status: Approved
Approval date: 15/09/2015
Contact: