Clinical trial NCT02159040: Phase II Study to Evaluate Overall Response in Patients With Higher Risk Myelodysplastic Syndromes (MDS) Treated With Azacitidine With or Without Deferasirox.
Official title: A 2-year, Multi-center, Phase II, Open-label, Fixed-dose, Randomized Comparative Trial of Azacitidine, With or Without Deferasirox in Patients With Higher Risk Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: High Risk MDS
Keywords: Int-2 MDS
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-06-09
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to compare the overall response rate (inclusive of complete response, partial response and hematologic improvement) per IWG 2006 criteria in patients with higher risk MDS treated with azacitidine with or without deferasirox achieved over the course of one year. Hematologic improvement must be maintained for at least 8 weeks.


Eligibility criteria: Inclusion Criteria:

Male or Female, age ≥ 18 years Patients with higher risk MDS with a blast count \< 20% at the time of screening IPSS Int-2 or High Risk Serum Ferritin ≥ 300 ng/mL at screening.

Sexually active women must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined as amenorrhea for at least 12 months)

Exclusion Criteria:

Patients currently receiving any therapy other than AZA for MDS (a ≥ 4 week washout period for any agent (excluding AZA) used to treat MDS prior to first dose of study treatment is required).

Patients who have received \> 2 cycles of AZA or decitabine at the time of randomization. Patients who have received iron chelation therapy within 1 month of screening.

Patients who have received growth factors within 1 month of screening. Patients who have received Revlimid within 1 month of screening. Patients who have undergone hematopoietic stem cell transplant. ECOG Performance Status \> 2 Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study treatment Patients with uncontrolled systemic hypertension Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or unstable cardiac or coronary artery disease not controlled by standard medical therapy Patients with a diagnosis of or history of clinically relevant ocular toxicity related to iron chelation Diagnosis of liver cirrhosis (either established diagnosis or diagnosis by liver biopsy or central ultrasound reading) Clinical or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive and ALT above the normal range). History of HIV positive test result (ELISA or Western blot) Presence of a surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug Patients with an active malignancy (currently or within the past two years) with the exception of basal cell skin carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ. History of drug or alcohol abuse within the 12 months prior to enrollment. History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative.

Patients with a known hypersensitivity to azacitidine, mannitol, or deferasirox. Calculated creatinine clearance \<40mL/min Serum creatinine greater than 1.5x ULN at screening Urine protein/creatinine ratio\> 1 AST or ALT greater than 3x ULN at screening Direct Bilirubin greater than 1.5x ULN at screening. Patients who received treatment with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days or are planning to receive other investigational drugs while participating in the study Patients participating in another therapeutic clinical trial Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment. Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after stopping AZA and should not father a child in this period.

Primary outcomes:
measure: Overall Response Rate Per IWG 2006 Criteria
timeFrame: 1 year
Secondary outcomes:
measure: Time to Response
timeFrame: up to 24 months
measure: Duration of Response
timeFrame: up to 24 months
measure: Progression Free Survival
timeFrame: Up to 24 months
measure: Overall Survival
timeFrame: up to 24 months
measure: Time to AML Transformation
timeFrame: Up to 24 months
measure: Change in Serum Ferritin
timeFrame: up to 24 months
measure: Incidence of Adverse Events
timeFrame: up to 24 months
measure: Rate of Infection
timeFrame: up to 24 months
measure: Prevalence of MDS/AML Related Gene Mutations
timeFrame: Baseline
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Hematology Oncology Services of Arkansas HOSA 2
state: Arkansas
city: Duarte
country: United States
facility: City of Hope National Medical Center Oncology
state: California
city: Baltimore
country: United States
facility: University of Maryland Medical Center UM Greenbaum Cancer Ctr (2)
state: Maryland
city: Rochester
country: United States
facility: Rochester General Hospital / Lipson Cancer Center Lipson Cancer Center
state: New York
city: Germantown
country: United States
facility: The Jones Clinic
state: Tennessee
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists IHO Corp
state: Utah
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: