Assessing the safety and tolerability of oral ruxolitinib in combination with 5-azacitidine in patients with advanced phase myeloproliferative neoplasms (MPN), including myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML) arising from MPN.
- Conditions
- Myeloproliferative neoplasms (MPN), including myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML) arising from MPNCancerMalignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissue
- Registration Number
- ISRCTN16783472
- Lead Sponsor
- The University of Birmingham (UK)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 58
Current participant inclusion criteria as of 01/08/2018:
For the Interventional component:
1. Age = 16 years old
2. A prior diagnosis of Essential Thrombocythaemia (ET), Polycythaemia Vera (PV) or Myelofibrosis (MF) with one of the following:
2.1. = 10% blasts in blood or bone marrow with or without dysplastic changes (MPN-AP) at baseline
2.2. = 20% blasts in blood or bone marrow (MPN-BP) at baseline
3. In need of treatment in the opinion of the investigator
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-3
5. Adequate liver and renal function, defined as:
5.1. Liver transaminases = 3 × ULN (AST/SGOT and ALT/SGPT)
5.2. Bilirubin <4 x ULN (Patients with elevated bilirubin due to Gilbert’s syndrome are eligible)
5.3. GFR = 40 ml/min
6. Willingness to undergo and ability to tolerate assessments during the study including bone marrow assessments and symptom assessments using patient reported outcome instruments
7. Able to give valid informed consent
For the Observational Component
1. Age = 16 years old
2. A prior diagnosis of ET, PV or MF with one of the following:
2.1. Blasts in blood or marrow 10-19%
with or without dysplastic changes (MPN-AP)
2.2 = 20% Blasts (MPN-BP)
2.3. Patients who are unwilling/unable to enter the interventional component and/or fail the interventional component entry criteria. This can include patients entered into studies with more aggressive therapy such as AML 17/19 as well as those receiving palliation only
Previous participant inclusion criteria:
For the Interventional component:
1. Age = 16 years old
2. A prior diagnosis of Essential Thrombocythaemia (ET), Polycythaemia Vera (PV) or Myelofibrosis (MF) with one of the following:
2.1. Blasts in blood or marrow 10-19%
with or without dysplastic changes (MPN-AP)
2.2. = 20% Blasts (MPN-BP)
3. In need of treatment in the opinion of the investigator
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-3
5. Platelet or red blood cell transfusion-dependent
6. Adequate liver and renal function, defined as:
6.1. Liver transaminases = 3 × ULN (AST/SGOT and ALT/SGPT)
6.2. Bilirubin <4 x ULN (Patients with elevated bilirubin due to Gilbert’s syndrome are eligible)
6.3. GFR = 40 ml/min
7. Willingness to undergo and ability to tolerate assessments during the study including bone marrow assessments and symptom assessments using patient reported outcome instruments
8. Able to give valid informed consent
For the Observational Component
1. Age = 16 years old
2. A prior diagnosis of ET, PV or MF with one of the following:
2.1. Blasts in blood or marrow 10-19%
with or without dysplastic changes (MPN-AP)
2.2 = 20% Blasts (MPN-BP)
2.3. Patients who are unwilling/unable to enter the interventional component and/or fail the interventional component entry criteria. This can include patients entered into studies with more aggressive therapy such as AML 17/19 as well as those receiving palliation only
Current participant exclusion criteria as of 01/08/2018:
For the Interventional Component:
1. Any co-morbidity that could limit compliance with the trial or any other condition (including laboratory abnormalities) that in the Investigators opinion will affect the patient’s participation in this trial
2.New York Heart Association Class II, III, or IV congestive heart failure
3. On-going cardiac dysrhythmias of grade 3, QTc prolongation >480 ms, or other factors that increase the risk of QT interval prolongation (e.g. heart failure, hypokalemia defined as serum potassium <3.0 mEq/L, family history of long QT interval syndrome)
4. Erythropoietic agent within 28 days prior to registration
5. Thrombopoietic agent within 14 days prior to registration
6. CYP3A4 inhibitor within 7 days prior to registration
7. Experimental treatment for AML or MPN within 14 days prior to registration (except Ruxolitinib and Hydroxycarbamide which can be taken up until study entry at the prestudy dose. Hydroxycarbamide must be stopped before the first scheduled day of treatment)
8. Previously received 5-azacitidine
9. Known contraindications to receiving azacitidine or ruxolitinib
10. Known HIV seropositivity
11. Known to have active hepatitis A, B, or C
12. Women who are pregnant or lactating. Patients of childbearing potential must have a negative pregnancy test prior to study entry
13. Patients and partners of childbearing potential not willing to use effective contraception for the duration of the study treatment and for three months after the last dose.
14. Active infection = grade 3 (CTCAE criteria) at trial entry
For the Observational Component:
No Exclusions planned.
Previous participant exclusion criteria:
For the Interventional Component:
1. Any co-morbidity that could limit compliance with the trial or any other condition (including laboratory abnormalities) that in the Investigators opinion will affect the patient’s participation in this trial
2.New York Heart Association Class II, III, or IV congestive heart failure
3. On-going cardiac dysrhythmias of grade 3, QTc prolongation >480 ms, or other factors that increase the risk of QT interval prolongation (e.g. heart failure, hypokalemia defined as serum potassium <3.0 mEq/L, family history of long QT interval syndrome)
4. Erythropoietic agent within 28 days prior to registration
5. Thrombopoietic agent within 14 days prior to registration
6. CYP3A4 inhibitor within 7 days prior to registration
7. Experimental treatment for AML or MPN within 14 days prior to registration (except Ruxolitinib and Hydroxycarbamide which can be taken up until study entry at the prestudy dose. Hydroxycarbamide must be stopped before the first scheduled day of treatment)
8. Previously received 5-azacitidine
9. Known contraindications to receiving azacitidine or ruxolitinib
10. Known HIV seropositivity
11. Known to have active hepatitis A, B, or C
12. Women who are pregnant or lactating. Patients of childbearing potential must have a negative pregnancy test prior to study entry
13. Patients and partners of childbearing potential not willing to use effective contraception for the duration of the study treatment and for three months after the last dose.
For the Observational Component:
No Exclusions planned.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To determine the MTD of ruxolitinib in combination with 5-azacitidine; Timepoint(s): Within 1 cycle of treatment
- Secondary Outcome Measures
Name Time Method