Dasatinib Holiday for Improved Tolerability

NCT02890784 | Completed Phase 3 DMC

• 1 other identifier: DasaHIT
• Study Type: interventional
• Target: 291
• Locations: 1 country
• Sites: 53

Brief Summary

Treatment optimization for patients with chronic myeloid leukemia (CML) with treatment naïve disease (1st line) and patients with resistance or intolerance against alternative Abl-Kinase Inhibitors (≥2nd line) (DasaHIT Trial (Dasatinib Holiday for Improved Tolerability))

Conditions

Myeloid Leukemia, Chronic

Outcome Measures

Primary Outcomes (2)

• cumulative toxicity score

  The cumulative toxicity score after two years of dasatinib treatment. More specifically, toxicity will be assessed taking into account both the rate of grade 2-4 toxicities and the cumulative severity of adverse events of specific interest. The following AEs of specific interest will be used to compose the cumulative toxicity score: 1. Pleural effusion 2. Fluid retention, other (edema, pericardial effusion, pulmonary arterial hypertension, congestive heart failure, pulmonary edema) 3. Hematological toxicity (neutropenia, thrombocytopenia, anemia) 4. Others (Musculoskeletal pain, skin toxicity (rash), gastrointestinal toxicity (nausea, diarrhea, abdominal pain, vomiting)

  month 24

• Rate of molecular Response

  The co-primary endpoint of the study is: rate of major molecular response (MMR) as assessed by BCR-ABL (IS \[International Score\] in %) -monitoring by 24 months to safeguard non-inferiority of the test cohort.

  month 24

Secondary Outcomes (2)

• Quality of life assessment

  month 24

• Rate of molecular Response

  6 and 12 months

Study Arms (2)

A. Standard arm

ACTIVE COMPARATOR

100mg dasatinib (SPRYCEL®) daily dose (QD) (7x100) (Standard therapy)

Drug: dasatinib (SPRYCEL®)

B. Study arm

EXPERIMENTAL

100mg dasatinib (SPRYCEL®) (QD) weekdays (1-5) only (5x100+2x0) (overall dose reduction per week)

Drug: dasatinib (SPRYCEL®)

Interventions

dasatinib (SPRYCEL®) DRUG

Treatment optimization for patients with chronic myeloid leukemia (CML)

A. Standard arm; B. Study arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of Ph+ chromosome \[t(9;22)(q34;q11)\].
• Ph negative cases or patients with variant translocations who are BCR-ABL positive in multiplex PCR4 will be also considered eligible.
• ECOG performance status ≤2.
• Age ≥ 18 years old (no upper age limit is given)
• Serum levels of potassium, magnesium and total calcium within the normal limits (≥LLN \[lower limit of normal\] and ≤ULN \[upper limit of normal\]). Correction of electrolytes' levels with supplements to meet enrolment criteria is allowed.
• AST and ALT ≤2.5 x ULN or 5.0 x ULN if considered due to leukemia
• Alkaline phosphatase ≤2.5 x ULN unless considered due to leukemia
• Total bilirubin ≤1.5 x ULN, except known Gilbert disease
• Serum creatinine ≤2 x ULN
• Written informed consent prior to any study procedures being performed.
• For 1st-line patients:
• Pre-treatment with hydroxyurea up to 6 months and imatinib or dasatinib for duration of up to 4 weeks is permitted.
• For ≥ 2nd-line patients:
• Patients with treatment failure according to the 2013 ELN Recommendations criteria3 or treatment intolerance as assessed by the investigator after prior treatment with TKIs other than dasatinib (imatinib, nilotinib, bosutinib, ponatinib).

You may not qualify if:

• Previous allogeneic stem cell transplantation (AlloSCT)
• Known impaired cardiac function, including any of the following:
• Congenital long QT syndrome
• History of or presence of clinically significant ventricular or atrial tachyarrhythmia
• QTc \>450 msec on screening ECG
• Myocardial infarction within 6 months prior to starting therapy
• Other clinical significant heart disease (e.g. unstable angina pectoris, congestive heart failure)
• Acute or chronic viral hepatitis with moderate or severe hepatic impairment (Child-Pugh scores \>6), even if controlled
• Other concurrent uncontrolled medical conditions (e.g., active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol
• Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric by-pass surgery)
• Concomitant medications known to be strong inducers or inhibitors of the CYP450 isoenzyme CYP3A4
• Patients who have undergone major surgery ≤2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• Patients who are pregnant or breastfeeding or women of reproductive potential not employing an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to administration of dasatinib. Post-menopausal women must be amenorrheic for at least 12 months in order to be considered of non-childbearing potential. Male and female patients must agree to employ an effective method of birth control throughout the study and for up to 3 months following discontinuation of study drug
• Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
• Active autoimmune disorder, including autoimmune hepatitis

Sponsors & Collaborators

• University of Jena: lead

Study Sites (53)

Uniklinik der RWTH Aachen

Aachen, 52074, Germany

Location

Gesundheitszentrum St. Marien GmbH

Amberg, 92224, Germany

Location

Gemeinschaftspraxis Dres. Klausmann

Aschaffenburg, 63739, Germany

Location

OnkoBer

Berlin, 10115, Germany

Location

Evangelisches Klinikum Bethel gGmbH

Bielefeld, 33611, Germany

Location

Universitätsklinikum Bonn

Bonn, 53111, Germany

Location

Klinikum Bremen-Mitte gGmbH

Bremen, 28177, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, 09113, Germany

Location

Gemeinschaftspraxis Mohm/Prange-Krex

Dresden, 01307, Germany

Location

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, 01307, Germany

Location

Helios St. Johannes Klinik Duisburg

Duisburg, 47166, Germany

Location

Gemeinschaftspraxis Erlangen

Erlangen, 91052, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Katholisches Karl-Leisner Klinikum

Goch, 47574, Germany

Location

MVZ Onkologische Kooperation Harz

Goslar, 38642, Germany

Location

ConMed GmbH

Göttingen, 37073, Germany

Location

Hämato-Onkologische Gemeinschaftspraxis Halberstadt

Halberstadt, 38820, Germany

Location

Universitätsklinikum Halle/S.

Halle, 06120, Germany

Location

Asklepios MVZ Onkologie

Hamburg, 22417, Germany

Location

MediProjekt GbR

Hanover, 30171, Germany

Location

St. Bernward Krankenhaus Hildesheim

Hildesheim, 31134, Germany

Location

Universitätsklinikum Jena

Jena, 07740, Germany

Location

Institut für med. Dokumentation, Gutachtenstellung, Gesundheitsförderung und Qualitätssicherung GbR

Kaiserslautern, 67655, Germany

Location

Städtisches Klinikum Karlsruhe gGmbH

Karlsruhe, 76133, Germany

Location

St. Vincentius-Kliniken Karlsruhe

Karlsruhe, 76137, Germany

Location

Onkologische Gemeinschaftspraxis

Kassel, 34119, Germany

Location

Klinikum Kassel

Kassel, 34125, Germany

Location

Städtisches Krankenhaus Kiel GmbH

Kiel, 24116, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, 24116, Germany

Location

InVo Institut für Versorgungsforschung

Koblenz, 56068, Germany

Location

MVZ Hämatologie und Onkologie

Krefeld, 47805, Germany

Location

Onkologische Schwerpunktpraxis

Kronach, 96317, Germany

Location

Onkologisches Zentrum

Lebach, Germany

Location

Studienzentrum UnterEms

Leer, 26789, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitätsmedizin Mannheim

Mannheim, 68169, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH

Marburg, 35043, Germany

Location

Stauferklinikum Schwäbisch Gmünd

Mutlangen, 73557, Germany

Location

Rotkreuzklinikum München

München, 80634, Germany

Location

Gemeinschaftspraxis Hämatologie/ Onkologie

München, 81241, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Hämatologisch-onkologische Schwerpunktpraxis

Neustadt am Rübenberge, 31535, Germany

Location

Klinikum Passau

Passau, 94032, Germany

Location

Kreiskliniken Reutlingen GmbH

Reutlingen, 72764, Germany

Location

Universitätsmedizin Rostock

Rostock, 18057, Germany

Location

Klinikum Südstadt Rostock

Rostock, 18059, Germany

Location

Hämatologie-Onkologie Stolberg

Stolberg, 52222, Germany

Location

Klinikum Mutterhaus der

Trier, 54290, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH

Villingen-Schwenningen, 78052, Germany

Location

Rems-Murr-Klinik Winnenden

Winnenden, 71364, Germany

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; 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

• Andreas Hochhaus, Prof.

  Jena University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Clinic of Internal Medicine II

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: September 7, 2016
• Study Start: August 1, 2016
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (53)