Track topics on Twitter Track topics that are important to you
Rationale/Purpose: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating young patients with acute lymphoblastic leukemia (ALL).
This trial is studying several different combination chemotherapy regimens to compare how well they work in treating young patients with ALL.
Primary study questions:
- Non high-risk (non-HR) precursor-B ALL (pB-ALL) patients with TEL/AML1-negative ALL or unknown TEL/AML1 status and flow cytometry minimal residual disease (MRD) in bone marrow on day 15 <0.1% or with TEL/AML1-positive ALL (randomized study question R1): Can the daunorubicin dose in Protocol IA be safely reduced by 50 % with a non-inferior EFS and a reduction of toxicity (treatment-related mortality and AE/SAE in Protocol I)?
- Patients with pB-ALL and risk group medium risk (MR) (randomized study question R2): Can the clinical outcome be improved by protracted asparagine depletion achieved through application of intensified PEG-L-asparaginase during reintensification and early maintenance?
- High-risk (HR) patients (as identified by day 33 - randomized study question RHR): Can the clinical outcome be improved by protracted exposure to PEG-L-asparaginase during Protocol IB?
Secondary study questions:
- Standard risk (SR) patients identified by at least one sensitive marker: Is the clinical outcome comparable to that obtained in SR patients (identified with two sensitive markers) in AIEOP-BFM ALL 2000, or can the outcome even be improved with the use of PEG-L-asparaginase instead of native E. coli L-ASP?
- T-ALL non-HR patients: Can the high level of outcome which was obtained for these patients in study AIEOP-BFM ALL 2000 be preserved or even improved with the use of PEG-L-ASP instead of native E. coli L-ASP?
- HR patients with persisting high MRD levels despite the use of the HR blocks in the intensified consolidation phase "MRD Non-Responders": Is it possible to improve the outcome and to achieve a further reduction of leukemic cell burden by administration of an innovative treatment schedule (DNX-FLA)?
- Patients participating in the randomized asparaginase studies (pB-ALL/MR, HR): Are asparaginase activity and asparaginase antibodies associated with development of allergic reactions, and do they have an effect on the outcome of the patients?
- What is the relative value of different methods of MRD monitoring in the definition of alternative stratification systems within a BFM-oriented protocol?
- T/non-HR: T-ALL in absence of any HR criteria (see below)
- pB/non-HR: pB-ALL in absence of any HR criteria (see below).
- SR (polymerase chain reaction(PCR)-MRD-SR (MRD-negative on day 33 and 78) or, if no PCR-MRD result available, FCM d15 < 0.1%)
- MR (no SR)
- HR: Prednisone poor-response (≥1000 blast cells/µl in peripheral blood on day 8), blast cells ≥10% in bone marrow on day 15 as measured by FCM, non-remission on day 33, positivity for MLL/AF4 or t(4;11), hypodiploidy (< 45 chromosomes), PCR-MRD-HR (MRD ≥10E-3 on day 78) or PCR-MRD-MR SER (only in pB-ALL, MRD ≥ 10-3 on day 33 and MRD positive at a level of < 10E-3 on day 78)
According to the risk group, patients receive the following chemotherapy elements:
T/non-HR: Protocol I, Protocol M, Protocol II and Maintenance pB/non-HR: Protocol I, Protocol M, Protocol II and Maintenance HR: Protocol I, HR-1', HR-2', HR-3', 3x Protocol III, Maintenance Patients of the HR group with PCR-MRD ≥10E-3 after element HR-3' are eligible for treatment with element DNX-FLA.
Protocol I Cytoreductive prephase: Prednisone (PDN) on days 1-7 and one dose of methotrexate (MTX) intrathecal (IT) on day 1 Protocol IA: Prednisone (PDN) on days 8 to 28 (21 days); vincristine (VCR) on days 8, 15, 22, 29 (4 doses); daunorubicin (DNR) on days 8, 15, 22 and 29 (4 doses); pegylated L-asparaginase (PEG-L-ASP) on days 12 and 26; MTX IT on days 12 and 33 and in case of blast cells in cerebrospinal fluid at diagnosis additional IT MTX is given on days 19 and 26.
Protocol IA': Only two doses of DNR on days 8 and 15 given to patients eligible for randomization R1 and randomized into the experimental arm Protocol IA-CPM: additional cyclophosphamide (CPM) on day 10 only in T-ALL patients with prednisone poor-response Protocol IA-Dexa (IAD): Dexamethasone (DXM) instead of PDN is given to all patients with T-ALL without any high-risk criteria as identified by day 8.
Protocol IB: CPM on days 36 and 64; cytarabine (ARA-C) on days 38-41, 45-48, 52-55 and 59-62; 6-mercaptopurine (6-MP) on days 36 to 63 (28 days); MTX IT on day 45 and 59 Protocol IB-ASP+: additional PEG-L-ASP on days 40, 47, 54, and 61 (4 doses) are given to the patients eligible for randomization RHR and randomized into the experimental arm.
Protocol M 6-MP on days 1- 56, high-dose MTX (HD-MTX) on days 8, 22, 36, 50 and MTX IT on days 8, 22, 36 and 50 Protocol II Protocol IIA: DXM on days 1 to 21 (21 days); VCR on days 8, 15, 22, 29 (4 doses); doxorubicine (DOX) on days 8, 15, 22 and 29 (4 doses); PEG-L-ASP on day 8 (1 dose); MTX IT on days 1 and 18 only in patients with initial CNS involvement.
Protocol IIA-ASP+: additional PEG-L-ASP on day 22 for patients eligible for randomization R2 and randomized into the experimental arm.
Protocol IIB: CPM on day 36; ARA-C on days 38-41 and 45-48; thioguanine (TG) on days 36 to 49 (14 days) and MTX IT on days 38 and 45.
Protocol IIB-ASP+: additional PEG-L-ASP on days 36 and 50 for eligible for randomization R2 and randomized into the experimental arm.
Protocol III DXM on days 1-15; VCR on days 1 and 8; DOX on days 1 and 8; PEG-L-ASP on day 1; CPM on day 15; ARA-C on days 17-20 and 24-27; TG on days 15 - 28 and MTX IT on days 17 and 24, also on day 1 in patients with initial CNS involvement HR-1' DXM on days 1-5; VCR on days 1 and 6; HD-MTX on day 1; CPM every 12 hours on days 2-4 (5 doses); HD-ARA-C every 12 hours on day 5 (2 doses); PEG-L-ASP on day 6, MTX IT on day 1 HR-2' DXM on days 1 to 5; VDS on days 1 and 6; HD-MTX on day 1; IFO every 12 hours on days 2-4 (5 doses); DNR on day 5; PEG-L-ASP on day 6; MTX IT on day 1 and 1 in patients with initial CNS involvement also day 5 HR-3' DXM on days 1-5; ARA-C 4 x on days 1-2 in 12 h intervals; etoposide (VP-16) every 12 hours on days 3-5 (5 doses); PEG-L-ASP on day 6; MTX IT on day 1 DNX-FLA Flucytosine (FLU) on days 1-5 (5 doses); HD-ARA-C on days 1 to 5 (5 doses); liposomal daunorubicin (DNX) on days 1, 3 and 5 (3 doses); MTX IT on day 1
Interim/Maintenance (until week 104):
6-MP p.o. daily; MTX p.o. once a week, doses adjusted to white blood cell count; PEG-L-ASP: every second week (6 doses), only for patients eligible for randomization R2 and randomized into the experimental arm; MTX IT every 6 weeks up to a total of 6 doses for the following subgroups (all CNS-negative):
- T-ALL (HR or non-HR) with < 2 years of age at start of maintenance,
- T-ALL, non-HR and initial WBC < 100 000/μl
- pB-ALL with PPR and/or FCM-MRD day 15 ≥ 10 % and/or PCR-MRDMR SER as only HR criteria
Radiotherapy Patients without CNS involvement and
- T-ALL/non-HR, WBC ≥ 100 000/μl, and age ≥ 2 years at start of pCRT or
- with risk group HR and age ≥ 2 years at start of pCRT except pB-ALL with PPR and/or FCM-MRD day 15 ≥ 10 % and/or PCR-MRD-MR SER as only HR criteria receive preventive cranial radiotherapy with 12 Gy
Patients with CNS involvement receive therapeutic cranial radiotherapy with 18 Gy (age 1 to <2 years 12 Gy).
Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
PEG-L-asparaginase, cyclophosphamide, cytarabine, daunorubicin hydrochloride, dexamethasone, doxorubicin hydrochloride, etoposide, ifosfamide, mercaptopurine, methotrexate, prednisone, thioguanine, vincristine sulfate, vindesine, daunoxome, fludarabine, R
The Sydney Children's Hospital, Centre for Children's Cancer and Blood Disorders
University of Schleswig-Holstein
Published on BioPortfolio: 2014-08-27T03:13:54-0400
The outcomes of children with lymphoblastic lymphoma (LBL) in China in our previous study were not unexpected. In this study, through further modification treatment protocols and strengthe...
RATIONALE: Drugs used in chemotherapy, such as prednisolone and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them fr...
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: ...
The primary objective of this study (TOTXVI) is to compare the clinical benefit, the pharmacokinetics, and the pharmacodynamics of polyethylene glycol-conjugated (PEG) asparaginase given i...
Ofatumumab in Combination With Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine Sulfate, and Dexamethasone Alternating With Ofatumumab in Combination With Cytarabine and Methotrexate in Treating Patients With Newly Diagnosed Mantle Cell Lymphoma
This phase II trial studies how well ofatumumab in combination with cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and dexamethasone alternating with ofatumumab in combi...
Indole-3-guanylhydrazone hydrochloride (LQM01) is a new derivative of aminoguanidine hydrochloride, an aromatic aminoguanidine.
The current standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) is an anthracycline plus cytarabine. Both anthracyclines and cytarabine have been associate...
Pulmonary oedema is recognised as a severe side effect of ritodrine hydrochloride. Recently, the number of twin pregnancies has been increasing. Few studies have reported the association between total...
Methamphetamine hydrochloride is 1 of the most widespread psycho-stimulants in the world. Nevertheless, its effect on pregnant women and their neonates has not been investigated extensively.
The objective was to evaluate the action of D. flagrans pellets in association with Levamisole Hydrochloride 5% for controlling sheep gastrointestinal nematodes in the northeastern Brazil. Three group...
A pharmaceutical preparation of sitagliptin phosphate and metformin hydrochloride that is used in the treatment of TYPE 2 DIABETES.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
A benzamide derivative that is used as a dopamine antagonist.
Used in the form of the hydrochloride as a reagent in ANALYTICAL CHEMISTRY TECHNIQUES.
4(1-Naphthylvinyl)pyridine hydrochloride. Cholinesterase inhibitor. Synonym: YuB 25.
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...