Optimization of Therapy in Adult Patients with Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma by Individualised, Targeted and Intensified Treatment

Goethe University

Status and phase: Active, not recruiting; Phase 3

Conditions: Lymphoblastic Lymphoma; Acute Lymphoblastic Leukemia

Treatments: Drug: Cytarabine; Drug: Cyclophosphamide; Drug: Methotrexate; Drug: Vindesine; Drug: Daunorubicin (DNR); Drug: Fludarabine; Drug: Vincristine; Drug: Adriamycin; Procedure: Stem cell transplantation; Drug: Rituximab; Drug: Prednisolone; Drug: PEG-Asparaginase; Drug: Dexamethasone; Procedure: Cranial irradiation; Drug: VP16; Drug: Imatinib; Drug: Mercaptopurine; Drug: Nelarabine; Drug: Idarubicin

Study type: Interventional

Funder types: Other

Identifiers

NCT02881086

GMALL08_2013

Details and patient eligibility

About

A phase IV study with the primary goal to optimize therapy of adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma (LBL) by dose and time intensive, pediatric based chemotherapy, risk adapted stem cell transplantation (SCT) and minimal residual disease (MRD) based individualised and intensified therapy. Study will further evaluate the role of asparaginase intensification, the extended use of rituximab and the use of nelarabine as consolidation therapy in T-ALL in a phase III-part of the study. Furthermore two randomisations will focus on the role of central nervous system (CNS) irradiation in combination with intrathecal therapy versus intrathecal therapy only in B-precursor ALL/LBL and the role of SCT in high-risk patients with molecular complete remission. Finally a new, dose reduced induction therapy in combination with Imatinib will be evaluated in Ph/BCR-ABL positive ALL.

Enrollment: 1,000 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Acute lymphoblastic leukemia (pro-B, common, pre-B, early T, thymic T, mature T)
• Lymphoblastic lymphoma (B or T-lineage)
• Age 18-55 yrs
• Written informed consent
• Adequate contraception as specified per protocol

Exclusion criteria

• Severe comorbidity or leukemia associated complications
• Late relapse of pediatric ALL or ALL as second malignancy
• Cytostatic pre-treatment
• Pregnancy or breast feeding
• Severe psychiatric illness or other circumstances which may compromise cooperation of the patient
• Participation in other clinical trials interfering with the study therapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

1,000 participants in 9 patient groups

Stratification I - Standard Risk (SR)/ High Risk (HR)

Other group

Description:

Induction and consolidation I therapy for standard and high risk patients, PH/BCR-ABL-negative Chemotherapy, immunotherapy, intrathecal prophylaxis, CNS irradiation according to randomisation I Drugs: Rituximab, Vincristine, Daunorubicin, Dexamethasone, Cyclophosphamide, Cytarabine, Mercaptopurine, PEG-Asparaginase, Methotrexate, Vindesine, VP16

Treatment:

Drug: Mercaptopurine

Drug: VP16

Drug: Dexamethasone

Drug: PEG-Asparaginase

Drug: Rituximab

Drug: Vincristine

Drug: Vindesine

Drug: Daunorubicin (DNR)

Drug: Methotrexate

Drug: Cyclophosphamide

Drug: Cytarabine

Stratification I - Philadelphia (PH)+

Other group

Description:

Induction and consolidation I therapy for PH+ patients Chemotherapy, immunotherapy, intrathecal prophylaxis Drugs: Rituximab, Vincristine, Imatinib, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, VP16

Treatment:

Drug: Imatinib

Drug: VP16

Drug: Dexamethasone

Drug: PEG-Asparaginase

Drug: Rituximab

Drug: Vincristine

Drug: Vindesine

Drug: Methotrexate

Drug: Cytarabine

Rand I - B-Lin + CNS Rad + i.th. MTX

Active Comparator group

Description:

Chemotherapy according to Stratification I SR/HR CNS prophylaxis: CNS irradiation 24 Gy, intrathecal Methotrexate

Treatment:

Procedure: Cranial irradiation

Drug: Methotrexate

Rand I - B-Lin + i.th. MTX

Experimental group

Description:

Chemotherapy according to Stratification I SR/HR CNS prophylaxis: intrathecal Methotrexate

Treatment:

Drug: Methotrexate

Stratification II - SR + MRD-neg

Other group

Description:

Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine, Dexamethasone

Treatment:

Drug: Nelarabine

Drug: Dexamethasone

Drug: PEG-Asparaginase

Drug: Prednisolone

Drug: Rituximab

Drug: Adriamycin

Drug: Vindesine

Drug: Methotrexate

Drug: Cyclophosphamide

Drug: Cytarabine

Stratification II - HR + MRD-neg

Other group

Description:

Chemotherapy or stem cell transplantation according to randomisation II

Treatment:

Drug: Nelarabine

Drug: PEG-Asparaginase

Drug: Prednisolone

Drug: Rituximab

Procedure: Stem cell transplantation

Drug: Adriamycin

Drug: Vindesine

Drug: Methotrexate

Drug: Cyclophosphamide

Drug: Cytarabine

Stratification II - SR/HR/PH+ + MRD-pos

Other group

Description:

Chemotherapy or targeted therapy, followed by stem cell transplantation Drugs: Fludarabine, Idarubicin, Cytarabine, Nelarabine

Treatment:

Drug: Idarubicin

Drug: Nelarabine

Drug: Fludarabine

Drug: Cytarabine

Randomisation II - HR + MRD-neg-SCT

Active Comparator group

Description:

Stem cell transplantation

Treatment:

Procedure: Stem cell transplantation

Randomisation II - HR + MRD-neg-SR-chemo

Experimental group

Description:

Chemotherapy, immunotherapy, intrathecal prophylaxis, consolidation II, reinduction, consolidation III - VI, maintenance Drugs: Rituximab, Dexamethasone, PEG-Asparaginase, Cytarabine, Methotrexate, Vindesine, Adriamycin, Prednisolone, Cyclophosphamide, Nelarabine

Treatment:

Drug: Nelarabine

Drug: Dexamethasone

Drug: PEG-Asparaginase

Drug: Prednisolone

Drug: Rituximab

Drug: Adriamycin

Drug: Vindesine

Drug: Methotrexate

Drug: Cyclophosphamide

Drug: Cytarabine