ALL-REZ BFM 2002: Multi-Center Study for Children With Relapsed Acute Lymphoblastic Leukemia

Study Overview
=================
Brief Summary
-----------------
The protocol ALL-REZ BFM 2002 aims at the optimization of treatment for children with relapsed acute lymphoblastic leukemia. The primary objective of study ALL-REZ BFM 2002 is the randomized comparison of a lower dosed and less intensive, but continuous consolidation therapy with conventional therapy administered in treatment blocks. Outcome measures are the reduction of minimal residual disease (MRD), event-free and overall survival, and the toxicity associated with each treatment strategy.

Detailed Description
-----------------
The study is based on the results of five consecutive trials performed by the ALL-REZ BFM study group since 1983. Thus the study meets the criteria of evidence-based therapy, which has been developed over nearly 20 years. Multi-agent chemotherapy in short intensive courses, which are separated by treatment-free intervals, has proved to be a successful form of induction and consolidation therapy. It is followed by preventative (or therapeutic) cranial irradiation and continuation therapy. A number of risk factors, particularly the time of relapse, site of relapse, and the ALL immunophenotype, allow the stratification of patients into a group that has an acceptable prognosis after treatment with chemotherapy alone and a second group that has a high risk of subsequent recurrence following the achievement of a second remission. The latter group requires further intensification of consolidation therapy by allogenic stem cell transplantation (SCT). To date, the indication for SCT has remained unclear for a large and heterogeneous group of patients with an intermediate prognosis. During the precursor study ALL-REZ BFM 96, however, the amount of minimal residual disease (MRD) determined quantitatively with clonal molecular markers after the second induction therapy element was shown to be a highly significant predictor of relapse-free survival. The primary objective of study ALL-REZ BFM 2002 is the randomized comparison of a lower dosed and less intensive, but continuous consolidation therapy with conventional therapy administered in treatment blocks. Outcome measures are the reduction of MRD, event-free and overall survival, and the toxicity associated with each treatment strategy. The secondary objectives include an improvement of the prognosis in the intermediate risk group using the stratification in treatment arms with and without allogenic SCT based on the MRD result after the second treatment element of induction therapy. An additional aim is to improve the remission induction rate in all groups by increasing the treatment intensity during induction. This is achieved by shortening the intervals between treatment blocks in keeping with the principles of guiding therapy as defined in the protocol. A series of biological companion studies aims to advance our understanding of the disorder and to establish novel prognostic factors that will allow a risk-adapted therapy.

Official Title
-----------------
ALL-REZ BFM 2002: Protocol for the Treatment of Children With Relapsed Acute Lymphoblastic Leukemia

Conditions
-----------------
Lymphoblastic Leukemia, Acute, Lymphoma, Non-Hodgkin

Intervention / Treatment
-----------------
* Procedure: R-Blocks
* Procedure: Protocol II-Ida


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Up to 18 years of age Morphologically confirmed diagnosis of relapsed non-B ALL or non-B non-Hodgkin lymphoma Exclusion Criteria: They have completed the 18th year of life at the time the relapse is diagnosed. Curative therapy is declined either by patient himself/herself or the respective legal guardian The patient is pregnant The patient is breast feeding Essential parts of the relapse therapy are declined either by the patient or his/her legal cannot be administered because of medical reasons. No consent is given for transmission of data The patient has a severe concomitant disease that does not allow treatment according to protocol (e.g. malformation syndromes, cardiac malformations, metabolic disorders).

Ages Eligible for Study
-----------------
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: R-Blöcke<br>Blocktherapie | Procedure: R-Blocks<br> <br> |
| Experimental: Prot-II-Ida<br>a | Procedure: Protocol II-Ida<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of MRD |  | a | 
| event-free and overall survival |  | a | 
| the toxicity associated with each treatment strategy |  | a | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of the prognosis in the intermediate risk group using the stratification in treatment arms with and without allogenic SCT based on the MRD result after the second treatment element of induction therapy |  | a | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
non-B ALL, relapse, treatment, Relapsed non-B ALL or non-B non-Hodgkin lymphoma