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Myeloid Leukemia, ChronicPhase 3DasaHITNCT02890784

Dasatinib Holiday for Improved Tolerability

A Phase 3 study testing dasatinib (SPRYCEL®) in people with Myeloid Leukemia, Chronic, run by University of Jena at 53 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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)) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myeloid Leukemia, Chronic
What is being tested?
dasatinib (SPRYCEL®)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
291 participants
Where
53 sitesGermany
Study dates
Aug 2016to 31 Mar 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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).

Who cannot join

  • 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
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  • 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
  • Known serious hypersensitivity reactions to dasatinib
  • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
  • Patients unwilling or unable to comply with the protocol.

Trial locations and contacts

53 sites in 1 country.

53 sites in 1 country

Germany53 sites

  • Uniklinik der RWTH Aachen

    Aachen, 52074

  • Gesundheitszentrum St. Marien GmbH

    Amberg, 92224

  • Gemeinschaftspraxis Dres. Klausmann

    Aschaffenburg, 63739

  • OnkoBer

    Berlin, 10115

  • Evangelisches Klinikum Bethel gGmbH

    Bielefeld, 33611

  • Universitätsklinikum Bonn

    Bonn, 53111

  • Klinikum Bremen-Mitte gGmbH

    Bremen, 28177

  • Klinikum Chemnitz gGmbH

    Chemnitz, 09113

  • Gemeinschaftspraxis Mohm/Prange-Krex

    Dresden, 01307

  • Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

    Dresden, 01307

  • Helios St. Johannes Klinik Duisburg

    Duisburg, 47166

  • Gemeinschaftspraxis Erlangen

    Erlangen, 91052

  • Universitätsklinikum Essen

    Essen, 45147

  • Universitätsklinikum Frankfurt

    Frankfurt, 60590

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau, 79106

  • Katholisches Karl-Leisner Klinikum

    Goch, 47574

  • MVZ Onkologische Kooperation Harz

    Goslar, 38642

  • ConMed GmbH

    Göttingen, 37073

  • Hämato-Onkologische Gemeinschaftspraxis Halberstadt

    Halberstadt, 38820

  • Universitätsklinikum Halle/S.

    Halle, 06120

  • Asklepios MVZ Onkologie

    Hamburg, 22417

  • MediProjekt GbR

    Hanover, 30171

  • St. Bernward Krankenhaus Hildesheim

    Hildesheim, 31134

  • Universitätsklinikum Jena

    Jena, 07740

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

    Kaiserslautern, 67655

  • Städtisches Klinikum Karlsruhe gGmbH

    Karlsruhe, 76133

  • St. Vincentius-Kliniken Karlsruhe

    Karlsruhe, 76137

  • Onkologische Gemeinschaftspraxis

    Kassel, 34119

  • Klinikum Kassel

    Kassel, 34125

  • Städtisches Krankenhaus Kiel GmbH

    Kiel, 24116

  • Universitätsklinikum Schleswig-Holstein

    Kiel, 24116

  • InVo Institut für Versorgungsforschung

    Koblenz, 56068

  • MVZ Hämatologie und Onkologie

    Krefeld, 47805

  • Onkologische Schwerpunktpraxis

    Kronach, 96317

  • Onkologisches Zentrum

    Lebach

  • Studienzentrum UnterEms

    Leer, 26789

  • Universitätsklinikum Leipzig

    Leipzig, 04103

  • Universitätsmedizin Mannheim

    Mannheim, 68169

  • Universitätsklinikum Gießen und Marburg GmbH

    Marburg, 35043

  • Rotkreuzklinikum München

    München, 80634

  • Gemeinschaftspraxis Hämatologie/ Onkologie

    München, 81241

  • Universitätsklinikum Münster

    Münster, 48149

  • Stauferklinikum Schwäbisch Gmünd

    Mutlangen, 73557

  • Hämatologisch-onkologische Schwerpunktpraxis

    Neustadt am Rübenberge, 31535

  • Klinikum Passau

    Passau, 94032

  • Kreiskliniken Reutlingen GmbH

    Reutlingen, 72764

  • Universitätsmedizin Rostock

    Rostock, 18057

  • Klinikum Südstadt Rostock

    Rostock, 18059

  • Hämatologie-Onkologie Stolberg

    Stolberg, 52222

  • Klinikum Mutterhaus der

    Trier, 54290

  • Universitätsklinikum Ulm

    Ulm, 89081

  • Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH

    Villingen-Schwenningen, 78052

  • Rems-Murr-Klinik Winnenden

    Winnenden, 71364

Other trials in Germany

About this study

Official title: 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)

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))

Read the detailed description

Dasatinib is indicated in Europe for:

  • Treatment of adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase
  • Chronic, accelerated or blast phase CML with resistance or intolerance to prior therapy including imatinib
  • Ph+ acute lymphoblastic leukemia (ALL) and lymphoid blast CML with resistance or intolerance to prior therapy Compared to imatinib, dasatinib in CML achieves faster and better responses. Dasatinib is known for its selected toxicities (fluid retention, edema, pleural effusion, and hematological toxicity) requiring dose reductions or treatment interruptions; these toxicities are more frequent in the first two years of treatment. A randomized dose optimization trial for QD dosing vs. BID dosing has demonstrated non-inferiority with regards to efficacy with an improved toxicity profile. In a pilot study, analyzing patients with dasatinib toxicity, a fixed dasatinib weekend holiday allowed safe toxicity management without impairing efficacy. Furthermore the alternated schedule was also able to improve response parameters in patients that had never achieved an acceptable response prior to the onset of dasatinib holiday dosing schedule. The biological rationale for a holiday dosing schedule is that dasatinib has shown an improved cell death of CML cells even after short exposure times; this improved cell death exceeds the killing rate observed with imatinib in vitro. In summary, the reported preclinical and clinical evidence indicates that efficacy seems to require adequate dasatinib Cmax, while low Cmin (five half-lives between doses) does not impair efficacy nor induces drug resistance. It is speculated that a weekend holiday, allowing a better tolerability, would improve patients' drug adherence. The Investigators hypothesize that a dasatinib holiday schedule (5x100mg+2x0mg weekly) compared to a regular dose (7x100mg weekly) will reduce the rate of clinically significant toxicity (e.g., fluid retention, hematological toxicity, musculoskeletal pain) by 20% observed within the first two years of treatment. The Investigators also hypothesize that the dasatinib holiday schedule is non-inferior to dasatinib regular dose in achieving the European LeukemiaNet (ELN) recommended levels of response within the first 24 months.
Being tested
dasatinib (SPRYCEL®)
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dasatinib (SPRYCEL®)Drug

    Treatment optimization for patients with chronic myeloid leukemia (CML)

Study groups in NCT02890784
Study groupRoleWhat they receive
A. Standard armActive comparator100mg dasatinib (SPRYCEL®) daily dose (QD) (7x100) (Standard therapy)
Receives: Drug: dasatinib (SPRYCEL®)
B. Study armExperimental100mg dasatinib (SPRYCEL®) (QD) weekdays (1-5) only (5x100+2x0) (overall dose reduction per week)
Receives: Drug: dasatinib (SPRYCEL®)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: month 24

  2. 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.

    Measured: month 24

Secondary outcomes (2)

  1. Quality of life assessment

    Quality of life assessment via Patient-Questionnaire.

    Measured: month 24

  2. Rate of molecular Response

    Rate of molecular response (MMR)as assessed by BCR-ABL (IS [International Score] in %) at 6 and 12 months.

    Measured: 6 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2016 (estimated)
  2. Study startAug 2016
  3. Primary completion31 Mar 2023
  4. Study completion31 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
291 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02890784
Sponsor's protocol ID
DasaHIT
Acronym
DasaHIT
Status last verified
May 2023
First submitted
14 Jan 2016
Last updated
10 May 2023
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing dasatinib (SPRYCEL®) in people with Myeloid Leukemia, Chronic, run by University of Jena at 53 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

cumulative toxicity score (time frame: month 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02890784.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2023.

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