Chronic Myelomonocytic Leukemia and secondary Acute myeloid leukemia MedDRA version: 20.0 Level: LLT Classification code 10054350 Term: Chronic myelomonocytic leukemia System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10028557 Term: Myeloid leukemia, acute System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Jakavi
Product Name: Ruxolitinib
Product Code: INC424
Pharmaceutical Form: Tablet
INN or Proposed INN: Jakavi
CAS Number: 1092939-17-7
Current Sponsor code: INC424
Other descriptive name:
Sponsors
Universität Leipzig
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must be diagnosed with postmyeloproliferative AML according to the 2008 World Health Organization criteria (Appendix A), irrespective of JAK2 mutation status or diagnosed with CMML with a white-blood-cell count above 13×10? cells /L. 2. Patients must give written informed consent according to local guidelines prior to any screening procedures. 3. Patients must not be eligible for another ongoing INC424 clinical trial at the trial site 4. Male or female patients =18 years 5. Patients with adequate liver function defined as direct bilirubin = 2.0 x ULN, and ALT = 2.5 x ULN. 6. Patients with adequate renal function defined as serum creatinine = 2 x ULN. 7. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. 8. Women of childbearing potential must have had a negative serum pregnancy test within 72 hours prior to the administration of study drug. They must agree to use effective contraceptive methods (doctors approved contraception) throughout the study and for 3 months following the date of the last dose of study medication. Female patients who are more than 2 years postmenopausal or have had a hysterectomy will not be consid-ered of childbearing potential. Males with female partner of childbearing potential must agree to use effective contraceptive methods (doctors ap-proved con-traception) throughout the study and should avoid fathering a child for 3 months fol-lowing the date of the last dose of study medica-tion. Adequate forms of contraception are double-barrier methods (con-doms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depot, or injectable contraceptives, intrauterine devices, and tubal ligation. 9. Patients must have recovered or stabilized sufficiently from adverse drug reactions associated with prior treatments before beginning treatment with INC424. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Any diagnosis of malignant disease within the previous 12 months (ex-cluding treated early stage squamous or basal cell carcinoma with no complications) 2. Impairment of gastrointestinal (GI) function or GI disease that may signifi-cantly alter the absorption of INC424 (e.g., ulcerative diseases, uncon-trolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection). 3. Hepatic tumors in the medical history 4. Patients with known active hepatitis A, B, C or who are HIV-positive. 5. Patients with coagulation parameters PT, PTT = 1.5 x ULN, If PT not done, than Quick = 1.5 x LLN 6. Patients with known hypersensitivity to INC424 or to its excipients or known or suspected hypersensitivity to azacitidine or mannitol. 7. Patients with serious concomitant medical illness: a. history of severe congestive heart failure [grade = 3 ac-cording to CTCAE] or b. clinically unstable ischemia or c. acute myocardial infarction in the previous six months or d. pulmonary hypertension [grade > 3 according to CTCAE] or e. severe cardiac arrythmias [grade > 3 according to CTCAE] or f. chronic pulmonary diseases [grade > 3 according to CTCAE] or g. uncontrolled hypertension or h. uncontrolled diabetes or i. uncontrolled severe infections [grade > 3 according to CTCAE] or j. any other severe or uncontrolled medical illness 8. Psychiatric illness that would prevent granting of informed consent 9. Patients receiving ongoing treatment with another investigational medication or having been treated with an investigational medication within 30 days of study drug treatment. 10. Patients who received treatment with azacitidine in the last 28 days prior to start of trial therapy 11. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until termination of gestation, confirmed by a positive ßHCG laboratory test (> 5 mIU/mL). 12. Patients with any concurrent condition that, in the Investigator’s opinion, would jeopardize the safety of the patient or compliance with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: Feasibility to administer INC424 alone or in combination with azacitidine on 4 patients. Phase II: To collect efficacy data on AML secondary to MPN and on CMML either with INC424 alone or in combination with azacitidine. ;Secondary Objective: • To evaluate outcome and quality of life on patients with AML secondary to MPN and on patients with CMML treated with INC424 and azacitidine • Evaluation of transfusion requirement ;Primary end point(s): Phase I: Tolerability and safety of INC424 treatment alone or in combination with azacytidine on four patients Clinical and laboratory parameters will be collected to evaluate study drug safety and toxicity. - Dose Limiting Toxicity (DLT) - Safety and tolerability will be collected by monitoring the frequency, duration and se-verity of all grade adverse events (AEs) by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v. 3 0) - performing physical exams (PE) - and evaluating changes in vital signs (VS) - ECOG performance status (PS) - serum chemistry and hematology results. - Grade 3 and 4 AEs, Serious Adverse Events (SAEs). - Frequency of dose interruptions and discontinuations due to AEs. Phase II: - Haematological Response defined as: Complete remissions (CR), Complete Remission with incomplete blood count recovery (CRi), Partial remissions (PR) and stable disease (SD in secondary AML - overall Response rate (ORR) ;Timepoint(s) of evaluation of this end point: Day 15, 28, 42, 56 and every 28 days of the following cycles At end of study Treatment and every 4 months until 1 years after end of study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Reduction of monocytes [10^9/L, %] • Reduction of blasts [10^9/L, %] • Frequency of appearance of dose limiting toxicity (DLT) of the sequential treatment • Event-free Survival one year / two years after start of therapy • Overall survival one year / two years after start of trial therapy • Number of required transfusions • Treatment effect on bone marrow fibrosis • Patients who achieve HCT (Time of transplant, Cytogenetics, other disease related and demographic factors) ;Timepoint(s) of evaluation of this end point: Day 15, 28, 42, 56 and every 28 days of the following cycles At end of study Treatment and every 4 months until 1 years after end of study treatment | — |
Countries
Germany
Contacts
Public ContactStudiensekretariat Hämatologie
Universität Leipzig
Outcome results
None listed