Phase II Study to Evaluate Overall Response in Patients With Higher Risk Myelodysplastic Syndromes (MDS) Treated With Azacitidine With or Without Deferasirox.

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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02159040

Enrollment

Registered

2014-06-09

Start date

2014-09-11

Completion date

2015-06-26

Last updated

2017-04-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

High Risk MDS

Keywords

Int-2 MDS

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.

Interventions

DRUGAzacitidine

SC or IV AZA at 75mg/m2 7 days/28 day cycle

DRUGAzacitidine plus Deferasirox

SC or IV AZA at 75mg/m2 7 days/28 day cycle DFX 10mg/kg/day

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Overall Response Rate Per IWG 2006 Criteria	1 year	ORR (inclusive of CR, PR and HI) per IWG 2006 criteria including erythroid response, platelet response and neutrophil response over the course of one year. Hematologic improvement must be maintained for at least 8 weeks in order to count as HI.

Secondary

Measure	Time frame	Description
Duration of Response	up to 24 months	Duration of response is defined as time from the date of the first observed hematologic improvement to the date of the first subsequent documented disease progression or relapse per IWG 2006 criteria.
Progression Free Survival	Up to 24 months	Progression free survival is defined as time from the date of the first dose of study treatment to the date of the first documented disease progression or relapse per IWG 2006 criteria.
Overall Survival	up to 24 months	Overall survival is defined as time from the date of the first dose of study treatment to the date of death from any cause.
Time to AML Transformation	Up to 24 months	Time to AML transformation is defined as time from the date of the first dose of study treatment to the date of the first documented bone marrow blast count ≥ 20% per WHO classification 1999.
Time to Response	up to 24 months	Time to response is defined as time from the date of the first dose of study treatment to the date of the first documented hematologic improvement.
Incidence of Adverse Events	up to 24 months	Incidence of adverse events (AEs) overall and by severity, and serious adverse events (SAEs).
Rate of Infection	up to 24 months	Median number of infections (positive bacterial, viral or fungal culture, or infection requiring IV antimicrobial, or infection resulting in hospitalization or death) in patients treated with azacitidine alone vs. azacitidine + deferasirox
Prevalence of MDS/AML Related Gene Mutations	Baseline	Prevalence of the following mutations in the study population (TP53, EZH2, ETV6, RUNX1, ASXL1, other mutation that is present in ≥ 5% of patients)
Change in Serum Ferritin	up to 24 months	Change in Serum Ferritin

Countries

United States

Participant flow

Recruitment details

Recruitment ended with patient death.Only one patient in trial. No analysis will ever be done.

Participants by arm

Arm	Count
Azacitidine 75mg/m2 7days/28 day cycle	1
Total	1

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	1

Baseline characteristics

Characteristic	Azacitidine
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	1 Participants
Age, Categorical Between 18 and 65 years	0 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	1 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	1 / 1
serious Total, serious adverse events	1 / 1

Outcome results

Primary

Overall Response Rate Per IWG 2006 Criteria

ORR (inclusive of CR, PR and HI) per IWG 2006 criteria including erythroid response, platelet response and neutrophil response over the course of one year. Hematologic improvement must be maintained for at least 8 weeks in order to count as HI.

Time frame: 1 year