Study of Frontline Dasatinib Plus Chemotherapy in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (PH+ALL)

NCT01724879 | Completed Phase 2 DMC

• 2 other identifiers: GMALL-PH-012010-022854-18
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 22

Brief Summary

The current standard treatment approach for young patients with Positive Acute Lymphoblastic Leukemia (Ph+ALL) is the combination of a chemotherapy protocol employing four to five cytotoxic agents typically used for ALL together with imatinib. It is recommended to propose allogeneic Standard Induction and Consolidation Therapy (SCT) to all eligible patients with a suitable donor and to continue imatinib with or without additional therapy in patients not undergoing SCT. This protocol is a study for newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia in patients aged 18 to 55 years. The objective of this strategy is to improve the overall results in the treatment of adult ALL with the addition of specific molecules to the common chemotherapeutic schedule.

Conditions

Philadelphia Positive Acute Lymphoblastic Leukemia

Keywords

philadelphia chromosome; BCR-ABL; ALL; acute lymphoblastic leukemia; dasatinib; Sprycel

Outcome Measures

Primary Outcomes (1)

• Treatment-related discontinuation of study treatment (Proportion of Patients)

  Day 120

Secondary Outcomes (3)

• Molecular complete remission rate (CR)

  Day 120

• Hematologic complete remission rate

  Day 120

• Grade III and IV txicity by Common Terminology Criteria for Adverse Events Version 3

  Day 120

Study Arms (1)

Dasatinib and chemotherapy

EXPERIMENTAL

Dasatinib, QD p.o. administration, day 1 to EOS

Drug: Dasatinib

Interventions

Dasatinib DRUG

Dasatinib p.o. + Chemotherapy (Dexamethasone, Cyclophosphamide, Vincristine, Methotroxate, 6-Mercapto-Purine, Cytarabine, Vindesine, VP16 (Etoposide))

Also known as: Sprycel (R), BMS-354825

Dasatinib and chemotherapy

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Confirmed new diagnosis of Philadelphia chromosome or BCR-ABL positive acute lymphoblastic leukemia
• Male or female patients aged 18-55 years
• Not previously treated except for prephase (corticosteroids, cyclophosphamide, single dose VCR will be permitted) therapy during establishment of the diagnosis
• Signed written inform consent, willingness and ability to comply with all study procedures
• Molecular detection of BCR-ABL transcripts
• Willingness of women of child-bearing potential (WOCBP) and male subjects whose sexual partners are WOCBP, to use an effective form of contraception (pearl index \< 1%), such as complete sexual abstinence, combined oral contraceptive, hormone IUCD, vaginal hormone ring, transdermal contraceptive patch, contraceptive implant or depot contraceptive injection in combination with a second method of contraception like a condom or a cervical cap / diaphragm with spermicide or surgical sterilisation (vasectomy) in male patients or male partners during the study and at least 6 months thereafter. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or surgical sterilization or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months).
• Negative pregnancy test for women of child-bearing potential.

You may not qualify if:

• Patients with ECOG status \> 2
• Patients with QTcF \> 470 ms
• Cardiac insufficiency NYHA grade III/IV, LEVF \< 50%, myocardial infarction within the past 6 months prior to study
• Active secondary malignancy requiring treatment
• Patients with active, uncontrolled bacterial, viral or fungal infection
• Known infection with HIV, Hepatitis B (except post vaccinal profile) or C
• Inadequate hepatic functions defined as ASAT or ALAT \> 2,5 times the institutional upper limit of normal and total bilirubin \> 2 fold the institutional upper limit unless considered to be due to organ involvement by the leukemia
• Concurrent severe diseases which exclude the administration of therapy
• Expected non-compliance or inability to understand informed consent
• Female patients who are pregnant or breast feeding
• Treatment with other investigational antileukemic agents after informed consent.

Sponsors & Collaborators

• Goethe University: lead

Study Sites (22)

Robert Bosch Krankenhaus

Stuttgart, Baden-Wurttemberg, 70376, Germany

Location

Klinikum der Universität Regensburg

Regensburg, Bavaria, 93042, Germany

Location

University Hospital of Frankfurt, Medical Dept. II

Frankfurt am Main, Hesse, 60590, Germany

Location

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

Universitätsklinik Münster

Münster, North Rhine-Westphalia, 48149, Germany

Location

Universitätsklinik Dresden

Dresden, Saxony, 01307, Germany

Location

Uniklinik Aachen

Aachen, 52074, Germany

Location

Charité Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Universitätsklinik Köln

Cologne, 50937, Germany

Location

University Hospital Düsseldorf

Düsseldorf, 40225, Germany

Location

Universitätsklinikum Göttingen

Göttingen, 37075, Germany

Location

Asklepios Klinik St. Georg

Hamburg, 20099, Germany

Location

Universität Leipzig, José-Carreras-Haus

Leipzig, 04103, Germany

Location

Universitätskliniken Mainz

Mainz, 55101, Germany

Location

Klinikum Mannheim

Mannheim, 68167, Germany

Location

Universitätsklinikum Großhadern

München, 81377, Germany

Location

Klinikum Nürnberg Nord

Nuremberg, 90419, Germany

Location

Klinikum Oldenburg

Oldenburg, 26133, Germany

Location

Universität Rostock

Rostock, 18055, Germany

Location

Medizinische Universitätsklinik Ulm

Ulm, 89070, Germany

Location

Medizinische Poliklinik der Universität Würzburg

Würzburg, 97070, Germany

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Philadelphia Chromosome

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Translocation, Genetic; Chromosome Aberrations; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Nicola Gökbuget, Dr.med

  Johann Wolfgang Goethe University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 3, 2012
• First Posted: November 12, 2012
• Study Start: November 1, 2011
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: January 26, 2022

Record last verified: 2022-01

Locations

DE (22)