To assess and compare efficacy (complete response [CR] rate and overall survival [OS]) between SGI-110 and TC in adults with previously untreated AML who are not considered candidates for intensive remission induction chemotherapy.
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Co-primary Endpoints
* CR rate based on modified International Working Group (IWG) 2003 AML Response
Criteria.
* OS, defined as the number of days from randomization to death.
Secondary outcome
Secondary Endpoints
* Composite CR rate (CRc = CR + Complete response with incomplete blood count
recovery [CRi] + Complete response with incomplete platelet recovery [CRp])
* Number of days alive and out of the hospital.
* Progression-free survival (PFS), defined as the number of days from
randomization to disease progression or death, whichever occurs first.
* Number of red blood cell (RBC) or platelet transfusions (units) over the
duration of the study treatment.
* Health-related quality of life (QOL) by EQ-5D (consisting of the EQ-5D-5L
descriptive system and the EQ Visual Analogue Scale [EQ VAS]).
* Duration of CR, defined as the time from first CR to time of relapse.
* Incidence and severity of adverse events (AEs).
* 30- and 60-day all-cause early mortality.
Background summary
See page 16 of the protocol, section 1.0 Introduction and Background
Study objective
To assess and compare efficacy (complete response [CR] rate and overall
survival [OS]) between SGI-110 and TC in adults with previously untreated AML
who are not considered candidates for intensive remission induction
chemotherapy.
Study design
This is a phase 3, multicenter, randomized, open-label study of SGI-110 versus
Treatment Choice (TC). Blinded central reading of marrow and disease response
will be performed.
Approximately 800 subjects from approximately 100-160 study centers will be
randomly assigned (1:1) to 1 of 2 groups:
* SGI-110: 60 mg/m2 SGI-110 given SC daily for 5 days (Days 1-5) in 28-day
cycles.
* Treatment Choice: subjects will be assigned (before randomization) by the
investigator to 1 of the following treatment regimens:
* 20 mg cytarabine given SC BID on Days 1-10 every 28 days.
* 20 mg/m2 decitabine given IV on Days 1-5 every 28 days.
* 75 mg/m2 azacitidine given IV or SC on Days 1-7 every 28 days.
Data will be reviewed by an independent Data Monitoring Committee (DMC) at
regular intervals primarily to evaluate safety during study conduct.
Intervention
* SGI-110: 60 mg/m2 SGI-110 given SC daily on Days 1-5 in 28-day cycles.
Treatment should be given for at least 6 cycles in the absence of unacceptable
toxicity or disease progression requiring alternative therapy. Beyond 6 cycles,
treatment should continue as long as the subject continues to benefit based on
investigator judgment.
* TC: before randomization, subjects will be assigned by the investigator to 1
of the following treatment regimens (dose, schedule, and administration route;
other treatment parameters, such as duration of treatment and dose adjustment
guidelines, should follow locally approved prescribing information and
institutional standard practice):
- 20 mg cytarabine given SC BID on Days 1-10 every 28 days.
- 20 mg/m2 decitabine given IV on Days 1-5 every 28 days.
- 75 mg/m2 azacitidine given IV or SC on Days 1-7 every 28 days.
Study burden and risks
Procedure-Related Risks or Discomforts
Subcutaneous Injection (SGI-110, cytarabine, and azacitidine):
Subcutaneous (SC) injection (when the drug is injected just under the skin) may
cause local pain, bruising, redness, swelling, or infection.
Intravenous Injection (decitabine and azacitidine):
Intravenous (IV) injection (when the drug is injected into a vein) may cause
local pain, bruising, or infection.
Blood Collection:
Blood will be collected at certain times during the study. Possible side
effects of blood collection are tenderness, pain, bleeding, bruising, infection
at the site where the needle goes into the skin, nausea, or feeling
lightheaded.
Bone Marrow Collection:
A bone marrow collection is done once before the patient start treatment and
may be repeated to see how the disease is doing and how the patient is
responding to the study treatment. A large needle is inserted through the skin
until it reaches the bone. Then, with a twisting motion, the needle is inserted
through the hard outer layer of the bone and into the marrow. Once the needle
is in the marrow, a syringe is attached and used to suck out some liquid bone
marrow. If a biopsy is needed, a slightly larger needle is used in a similar
manner. For both procedures, anesthetic medicine is injected to numb the area.
After the needle is taken out, the patient might be asked to lie flat for 5-10
minutes and to put pressure over the site where the needle went in. After that,
if there is no bleeding, the patient can resume normal activities.
The patient may have stinging or burning when the anesthetic is injected, pain
when marrow is withdrawn, and soreness or redness or both at the site. Side
effects the patient might have are fever, bleeding, swelling, or infection.
Electrocardiogram (ECG):
There may be some pulling on the patient's skin or irritation when the adhesive
patches are removed.
The side effects of SGI-110, decitabine, cytarabine and azacitidine are
described in the patient information and informed consent form.
Rosewood Drive, Suite 200 4420
Pleasanton CA 94588
US
Rosewood Drive, Suite 200 4420
Pleasanton CA 94588
US
Listed location countries
Age
Inclusion criteria
1. Able to understand and comply with study procedures, and provides written informed consent before any study-specific procedure.
2. Cytologically or histologically confirmed diagnosis of AML (except M3 acute promyelocytic leukemia) according to the 2008 World Health Organization (WHO) classification (bone marrow or peripheral blood blast counts *20%).
3. Performance status (ECOG) of 0-3.
4. Adults with previously untreated AML except for hydroxyurea or corticosteroids. Prior hydroxyurea or lenalidomide treatment for myelodysplastic syndrome (MDS) is allowed.
5. Not considered candidates for intensive remission induction chemotherapy at time of enrollment based on
EITHER:
a. *75 years of age
OR
b. <75 years of age with at least 1 of the following:
i. Poor performance status (ECOG) score of 2-3.
ii. Clinically significant heart or lung comorbidities, as reflected by at least 1 of:
1) Left ventricular ejection fraction (LVEF) *50%.
2) Lung diffusing capacity for carbon monoxide (DLCO) *65% of expected.
3) Forced expiratory volume in 1 second (FEV1) *65% of expected.
4) Chronic stable angina or congestive heart failure controlled with medication.
iii. Liver transaminases >3 × upper limit of normal (ULN).
iv. Other contraindication(s) to anthracycline therapy (must be documented).
v. Other comorbidity the investigator judges incompatible with intensive remission induction
chemotherapy, which must be documented and approved by the study medical monitor before
randomization.
6. Creatinine clearance as estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas *30 mL/min.
7. Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures during the study and for at least 3 months after completing treatment and must agree not to become pregnant or father a child while receiving treatment with SGI-110 and for at least 3 months after completing treatment.
Exclusion criteria
1. Candidate for intensive remission induction chemotherapy at the time of enrollment.
2. Candidate for best supportive care only, ie, not a candidate for any active therapy with the TC comparators.
3. Known extramedullary central nervous system (CNS) AML.
4. Second malignancy currently requiring active therapy except breast or prostate cancer stable on or responding to endocrine therapy.
5. Prior treatment with decitabine or azacitidine.
6. Hypersensitivity to decitabine, azacitidine, cytarabine, SGI-110, or any of their excipients.
7. Treated with any investigational drug within 2 weeks of the first dose of study treatment.
8. Total serum bilirubin >2.5 × ULN, except for subjects with Gilbert's Syndrome for whom direct bilirubin is <2.5 × ULN, or liver cirrhosis or chronic liver disease Childs-Pugh B or C.
9. Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed.
10. Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol.
11. Refractory congestive heart failure unresponsive to medical treatment; active infection resistant to all antibiotics; or advanced pulmonary disease requiring >2 liters per minute (LPM) oxygen.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-001233-89-NL |
| ClinicalTrials.gov | NCT02348489 |
| CCMO | NL51836.041.15 |