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NCT01498445

An Open-Label, Phase I/II Study of Two Different Schedules of Dasatinib (Sprycel) and Decitabine (Dacogen) Used in Combination for Patients With Accelerated or Blastic Phase Chronic Myelogenous Leukemia (Protocol CA180357)

Terminated Phase 1, PHASE2 Results posted Last updated 22 October 2020
What this trial tests

Phase 1, PHASE2 trial testing Dasatinib in Leukemia in 32 participants. Terminated before completion.

Timeline
12 June 2012
Primary endpoint
24 September 2019
24 September 2019

Quick facts

Lead sponsorM.D. Anderson Cancer Center
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment32
Start date12 June 2012
Primary completion24 September 2019
Estimated completion24 September 2019
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

M.D. Anderson Cancer Center — full company profile →

Who can join

18 and older, any sex, with Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Ph I Study: Maximum Tolerated Dose (MTD) Dasatinib Primary · End of first 28-day cycle

Maximum tolerated dose (MTD) defined as highest dose at which 0 of 3 or \</= 1/6 participant experience a first cycle dose limiting toxicity (DLT).

GroupValue95% CI
Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2NA
Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2NA
Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2140
Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2140
Number of Participants With Hematologic Responses During First 3 Months of Treatment Secondary · 3 months

Number of participants with hematologic response (HR) to therapy during first 3 months of combination dasatinib and decitabine therapy, where HR defined as any hematologic response observed during the first 3 months of treatment. Overall Hematologic Response (OHR) is defined as complete hematologic response (CHR), no evidence of leukemia (NEL) or minor hematologic response (MiHR)

GroupValue95% CI
Phase I - Dasatinib 100 mg + Decitabine 10 mg/m23
Phase I - Dasatinib 100 mg + Decitabine 20 mg/m21
Phase I - Dasatinib 140 mg + Decitabine 10 mg/m25
Phase I - Dasatinib 140 mg + Decitabine 20 mg/m24
Phase II - Dasatinib 140 mg + Decitabine 10 mg/m23
Phase II - Dasatinib 140 mg + Decitabine 20 mg/m23
Overall Survival Secondary · Up to seven years

Overall Survival will be measured from the date treatment is started to the date of death or last follow-up.

GroupValue95% CI
Phase I - Dasatinib 100 mg + Decitabine 10 mg/m212.00.6 – 36.8
Phase I - Dasatinib 100 mg + Decitabine 20 mg/m27.02.3 – 82.8
Phase I - Dasatinib 140 mg + Decitabine 10 mg/m257.80.9 – 79.4
Phase I - Dasatinib 140 mg + Decitabine 20 mg/m258.23.6 – 58.2
Phase II - Dasatinib 140 mg + Decitabine 10 mg/m262.06.0 – 62.0
Phase II - Dasatinib 140 mg + Decitabine 20 mg/m237.59.6 – 37.5
Duration of Response Secondary · up to seven years

Duration of Response will be measured from the date the given response is achieved to the date the response is first known to be lost

GroupValue95% CI
Phase I - Dasatinib 100 mg + Decitabine 10 mg/m236.81.2 – 36.8
Phase I - Dasatinib 100 mg + Decitabine 20 mg/m28282 – 82
Phase I - Dasatinib 140 mg + Decitabine 10 mg/m257.8.09 – 79.4
Phase I - Dasatinib 140 mg + Decitabine 20 mg/m25837 – 58
Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2611.5 – 61.0
Phase II - Dasatinib 140 mg + Decitabine 20 mg/m23730 – 37

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to seven years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2
Serious: 3/4 (75%)
Deaths: 1/4
Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2
Serious: 3/3 (100%)
Deaths: 1/3
Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2
Serious: 7/8 (88%)
Deaths: 2/8
Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2
Serious: 6/8 (75%)
Deaths: 0/8
Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2
Serious: 3/4 (75%)
Deaths: 0/4
Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2
Serious: 4/5 (80%)
Deaths: 0/5

Serious adverse events (34 terms)

ReactionSystemPhase I - Dasatinib 100 mg…Phase I - Dasatinib 100 mg…Phase I - Dasatinib 140 mg…Phase I - Dasatinib 140 mg…Phase II - Dasatinib 140 m…Phase II - Dasatinib 140 m…
FeverGeneral disorders
Neutropenic FeverBlood and lymphatic system disorders
Lung InfectionInfections and infestations
Respiratory FailureRespiratory, thoracic and mediastinal disorders
Abdominal PainGeneral disorders
Acute Kidney InjuryRenal and urinary disorders
Adult Respiratory Distress SyndromeRespiratory, thoracic and mediastinal disorders
AnemiaBlood and lymphatic system disorders
Blood and Lymphatic System DisordersBlood and lymphatic system disorders
Bone PainMusculoskeletal and connective tissue disorders
Cardiac ArrestCardiac disorders
Chest PainCardiac disorders
ConfusionPsychiatric disorders
DiarrheaGastrointestinal disorders
Gastric HemorrhageGastrointestinal disorders
General Administration SiteGeneral disorders
HeadacheNervous system disorders
Heart FailureCardiac disorders
HypertensionVascular disorders
HypotensionVascular disorders
InfectionInfections and infestations
LeukocytosisBlood and lymphatic system disorders
Myocardial InfarctionCardiac disorders
PancreatitisGastrointestinal disorders
Periorbital EdemaSkin and subcutaneous tissue disorders
Other adverse events (33 terms — click to expand)

ReactionSystemPhase I - Dasatinib 100 mg…Phase I - Dasatinib 100 mg…Phase I - Dasatinib 140 mg…Phase I - Dasatinib 140 mg…Phase II - Dasatinib 140 m…Phase II - Dasatinib 140 m…
HeadacheNervous system disorders
InfectionInfections and infestations
ConstipationGastrointestinal disorders
FatigueGeneral disorders
NauseaGastrointestinal disorders
NeutropeniaInvestigations
PainGeneral disorders
RashSkin and subcutaneous tissue disorders
AnxietyPsychiatric disorders
DiarrheaGastrointestinal disorders
EdemaGeneral disorders
FeverGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
HypokalemiaMetabolism and nutrition disorders
MucositisGastrointestinal disorders
ThrombocytopeniaInvestigations
VomitingGastrointestinal disorders
Hot FlashesVascular disorders
Acute Kidney InjuryRenal and urinary disorders
Chest PainCardiac disorders
Elevated AmylaseInvestigations
Elevated LipaseInvestigations
HyperbilirubinemiaInvestigations
HypercalcemiaMetabolism and nutrition disorders
HyperkalemiaMetabolism and nutrition disorders
HypotensionVascular disorders
Neutropenic FeverBlood and lymphatic system disorders
Pericardial EffusionCardiac disorders
HemorrhageGeneral disorders
Weight GainInvestigations
Peripheral NeuropathyNervous system disorders
Pleural EffusionRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Fever, Neutropenic Fever, Lung Infection, Respiratory Failure, Abdominal Pain, Acute Kidney Injury, Adult Respiratory Distress Syndrome, Anemia.

Data from ClinicalTrials.gov NCT01498445 adverse events section.

Sponsor's own description

The goal of this clinical research study is to learn if combining Sprycel (dasatinib) and Dacogen (decitabine) can help to control Chronic Myeloid Leukemia (CML). The dose level of decitabine will also be studied. Dasatinib is designed to block the protein that is responsible for chronic myeloid leukemia. Decitabine is designed to affect the mechanism that cells use to control the expression of certain genes, some of which are important in the progression of CML. This is an investigational study. Dasatinib is FDA approved and commercially available for the treatment of patients with certain types of CML. Decitabine is FDA approved for the treatment of patients with myelodysplastic syndrome. The combination of these drugs to treat CML is investigational. Up to 84 patients will take part in this study. All will be enrolled at MD Anderson.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Going back to class I: MHC and immunotherapies for childhood cancer.
    Haworth KB, Leddon JL, Chen CY, Horwitz EM, et al · · 2015 · cited 58× · PMID 25524394 · DOI 10.1002/pbc.25359
  2. Chronic myeloid leukemia stem cells: targeting therapeutic implications.
    Mojtahedi H, Yazdanpanah N, Rezaei N. · · 2021 · cited 53× · PMID 34922630 · DOI 10.1186/s13287-021-02659-1
  3. Concise Review: Chronic Myeloid Leukemia: Stem Cell Niche and Response to Pharmacologic Treatment.
    Arrigoni E, Del Re M, Galimberti S, Restante G, et al · · 2018 · cited 52× · PMID 29418079 · DOI 10.1002/sctm.17-0175
  4. Next-generation sequencing identifies major DNA methylation changes during progression of Ph+ chronic myeloid leukemia.
    Heller G, Topakian T, Altenberger C, Cerny-Reiterer S, et al · · 2016 · cited 45× · PMID 27211271 · DOI 10.1038/leu.2016.143
  5. Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities.
    Flis S, Chojnacki T. · · 2019 · cited 39× · PMID 30880916 · DOI 10.2147/dddt.s191303
  6. Phase I/II study of dasatinib in combination with decitabine in patients with accelerated or blast phase chronic myeloid leukemia.
    Abaza Y, Kantarjian H, Alwash Y, Borthakur G, et al · · 2020 · cited 36× · PMID 32681739 · DOI 10.1002/ajh.25939
  7. Potential Approaches <i>Versus</i> Approved or Developing Chronic Myeloid Leukemia Therapy.
    Andretta E, Costa C, Longobardi C, Damiano S, et al · · 2021 · cited 23× · PMID 34993151 · DOI 10.3389/fonc.2021.801779
  8. Pharmacology of tyrosine kinase inhibitors in chronic myeloid leukemia; a clinician's perspective.
    Pushpam D, Bakhshi S. · · 2020 · cited 14× · PMID 31900888 · DOI 10.1007/s40199-019-00321-z

Verify or expand the search:

Other trials of Dasatinib

Trials testing the same drug.

Other recruiting trials for Leukemia

Currently open trials in the same condition.

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Trials by the same sponsor.

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