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

Primary Purpose

Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma

Status

Active

Phase

Phase 3

Locations

Germany

Study Type

Interventional

Intervention

Rituximab

Nelarabine

PEG-Asparaginase

Cranial irradiation

Imatinib

Idarubicin

Dexamethasone

Cyclophosphamide

Fludarabine

Vincristine

Mercaptopurine

VP16

Daunorubicin (DNR)

Methotrexate

Stem cell transplantation

Cytarabine

Vindesine

Adriamycin

Prednisolone

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring Acute lymphoblastic leukemia, Lymphoblastic lymphoma, Nelarabine, BCR-ABL, MRD, PEG-Asparaginase, Rituximab

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept 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

Sites / Locations

University Hospital of Frankfurt (Main)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Other

Active Comparator

Experimental

Other

Active Comparator

Experimental

Arm Label

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

Stratification I - Philadelphia (PH)+

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

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

Stratification II - SR + MRD-neg

Stratification II - HR + MRD-neg

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

Randomisation II - HR + MRD-neg-SCT

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

Arm 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

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

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

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

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

Chemotherapy or stem cell transplantation according to randomisation II

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

Stem cell transplantation

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

Outcomes

Primary Outcome Measures

Event free survival

Secondary Outcome Measures

Time until consolidation treatment I

Disease free survival

Full Information

NCT ID

NCT02881086

First Posted

August 4, 2016

Last Updated

July 17, 2023

Sponsor

Goethe University

1. Study Identification

Unique Protocol Identification Number

NCT02881086

Brief Title

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

Official Title

Treatment Optimization in Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukemia (ALL) 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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 2016 (Actual)

Primary Completion Date

August 2022 (Actual)

Study Completion Date

July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Goethe University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma

Keywords

Acute lymphoblastic leukemia, Lymphoblastic lymphoma, Nelarabine, BCR-ABL, MRD, PEG-Asparaginase, Rituximab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1000 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Other

Arm Description

Arm Title

Stratification I - Philadelphia (PH)+

Arm Type

Other

Arm Description

Arm Title

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

Arm Type

Active Comparator

Arm Description

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

Arm Title

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

Arm Type

Experimental

Arm Description

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

Arm Title

Stratification II - SR + MRD-neg

Arm Type

Other

Arm Description

Arm Title

Stratification II - HR + MRD-neg

Arm Type

Other

Arm Description

Chemotherapy or stem cell transplantation according to randomisation II

Arm Title

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

Arm Type

Other

Arm Description

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

Arm Title

Randomisation II - HR + MRD-neg-SCT

Arm Type

Active Comparator

Arm Description

Stem cell transplantation

Arm Title

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

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Rituximab

Intervention Type

Drug

Intervention Name(s)

Nelarabine

Intervention Type

Drug

Intervention Name(s)

PEG-Asparaginase

Intervention Type

Procedure

Intervention Name(s)

Cranial irradiation

Intervention Type

Drug

Intervention Name(s)

Imatinib

Intervention Type

Drug

Intervention Name(s)

Idarubicin

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Intervention Type

Drug

Intervention Name(s)

Vincristine

Intervention Type

Drug

Intervention Name(s)

Mercaptopurine

Intervention Type

Drug

Intervention Name(s)

VP16

Intervention Type

Drug

Intervention Name(s)

Daunorubicin (DNR)

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Intervention Type

Procedure

Intervention Name(s)

Stem cell transplantation

Intervention Type

Drug

Intervention Name(s)

Cytarabine

Intervention Type

Drug

Intervention Name(s)

Vindesine

Intervention Type

Drug

Intervention Name(s)

Adriamycin

Intervention Type

Drug

Intervention Name(s)

Prednisolone

Primary Outcome Measure Information:

Title

Event free survival

Time Frame

3.5 years

Secondary Outcome Measure Information:

Title

Time until consolidation treatment I

Time Frame

approximately 70 days

Title

Disease free survival

Time Frame

1 year

Other Pre-specified Outcome Measures:

Title

Hematological remission rate

Time Frame

after induction, approximately 6-8 weeks from diagnosis

Title

Molecular remission rate

Time Frame

after induction and consolidation, approximately 6-8 weeks from diagnosis

Title

Results of the positron emission tomography (PET) based remission evaluation

Time Frame

after consolidation, approximately 8-10 weeks

Title

Remission duration

Time Frame

up to 10 years

Title

Relapse rate

Time Frame

up to 10 years

Title

Overall survival

Time Frame

up to 10 years

Title

Relapse location

Time Frame

at timepoint of relapse (up to 10 years)

Title

Early death

Time Frame

during induction, approximately 6-8 weeks from diagnosis

Title

Death in clinical remission (CR)

Time Frame

during treatment, up to approximately 2.5 years from diagnosis

Title

Comorbidities according to Charlson Score

Time Frame

up to 2.5 years

Title

Quality of life assessed by QLQ-C30

Time Frame

up to 2.5 years

Title

Eastern Cooperative Oncology Group (ECOG) under therapy

Time Frame

up to 2.5 years

Title

Toxicity assessed by CTCAE v4.03

Time Frame

up to 2.5 years

Title

Results of the Dementia Detection (DemTect) test

Time Frame

up to 2.5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nicola Gökbuget, Dr. med.

Organizational Affiliation

University Hospital of Frankfurt (Main)

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital of Frankfurt (Main)

City

Frankfurt (Main)

ZIP/Postal Code

60590

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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