Guadecitabine With or Without Idarubicin or Cladribine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Four-Arm Randomized Phase II Study of SGI-110: 5 Days, Versus 10 Days, Versus 5 Days + Idarubicin, Versus 5 Days + Cladribine, in Previously Untreated Patients >/= 70 Years With Acute Myeloid Leukemia

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02096055

Enrollment

Registered

2014-03-26

Start date

2014-04-04

Completion date

2020-11-24

Last updated

2024-08-27

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

Conditions

Untreated Adult Acute Myeloid Leukemia

Brief summary

This randomized phase II trial studies how well guadecitabine with or without idarubicin or cladribine works in treating older patients with previously untreated acute myeloid leukemia. Guadecitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin and cladribine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether guadecitabine with or without idarubicin or cladribine is more effective in treating older patients with previously untreated acute myeloid leukemia.

Detailed description

PRIMARY OBJECTIVES: I. To determine the complete remission (CR) rate, remission duration, leukemia-free survival, and survival in patients \>= 70 years with previously untreated acute myeloid leukemia (AML) with 4 different guadecitabine (SGI-110) single agent and SGI-110 based combination regimens. II. To determine the safety profile and tolerability of the 4 SGI-110 single agent and SGI-110 based combination regimens in patients \>= 70 years of age with previously untreated AML. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: INDUCTION THERAPY: Patients receive guadecitabine subcutaneously (SC) on days 1-5. Courses repeat every 4-6 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR or CR with incomplete platelet recovery (CRp) continue on to Maintenance therapy; patients not achieving CR or complete remission with incomplete hematologic recovery (CRi) but deriving clinical benefit may continue to Maintenance therapy at the discretion of the Principal Investigator (PI). MAINTENANCE THERAPY: Patients receive guadecitabine as in Induction therapy. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. ARM II (CLOSED): INDUCTION THERAPY: Patients receive guadecitabine SC on days 1-10. Courses repeat every 4-6 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR or CRp continue on to Maintenance therapy; patients not achieving CR or CRi but deriving clinical benefit may continue to Maintenance therapy at the discretion of the PI. MAINTENANCE THERAPY: Patients receive guadecitabine SC on days 1-5 (days 1-10 of courses 1 and 2). Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. ARM III: INDUCTION THERAPY: Patients receive guadecitabine SC on days 1-5 and idarubicin intravenously (IV) over up to 1 hour on days 1-2. Courses repeat every 4-6 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR or CRp continue on to Maintenance therapy; patients not achieving CR or CRi but deriving clinical benefit may continue to Maintenance therapy at the discretion of the PI. MAINTENANCE THERAPY: Patients receive guadecitabine SC on days 1-5 and idarubicin IV over up to 1 hour on day 1. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. ARM IV (CLOSED): INDUCTION THERAPY: Patients receive guadecitabine SC and cladribine IV over up to 1 hour on days 1-5. Courses repeat every 4-6 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR or CRp continue on to Maintenance therapy; patients not achieving CR or CRi but deriving clinical benefit may continue to Maintenance therapy at the discretion of the PI. MAINTENANCE THERAPY: Patients receive guadecitabine SC and cladribine IV over up to 1 hour on days 1-5. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every month.

Interventions

DRUGCladribine

Given IV

DRUGGuadecitabine

Given SC

DRUGIdarubicin

Given IV

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

70 Years to No maximum

Healthy volunteers

Inclusion criteria

* Previously untreated AML patients, except those who have received prior therapy with hydroxyurea, single agent chemotherapy (e.g. decitabine), hematopoietic growth factors, biological or targeted therapies are allowed * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Sign a written informed consent form * Total bilirubin =\< 2 mg/dL * Serum glutamate pyruvate transaminase (SGPT) or serum glutamic oxaloacetic transaminase (SGOT) =\< 4 x upper limit of normal (ULN) * Creatinine clearance of \>= 50 mL/min (estimated by the Cockcroft-Gault \[C-G\] formula) * Male patients must use an effective contraceptive method during the study and for a minimum of 8 weeks after study treatment * Baseline left ventricular ejection fraction (LVEF) \>= 40%

Exclusion criteria

* Patients with \>= New York Heart Association (NYHA) grade 3 heart disease as assessed by history and/or physical examination * Patients who received more than one full course of prior hypomethylating agents azacitidine or decitabine * Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment * Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) * Pregnant or lactating patients * Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results * Any concurrent malignancy with the exception of the following: a) patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed; b) patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With a Complete Response	Up to 4 years, 3 months	Complete Response = Complete Remission (CR) + Complete Remission without blood count recovery (CRi) - CR: Neutrophil count \>/= 1.0 x 10\^9/L and platelet count \>/= 100 x 10\^9/L, and normal bone marrow differential (\</+ 5% blasts). (CRi): Peripheral blood and bonemarrow results as for CR, but with platelet counts of \< 100 x 109/L or ANC \< 1.0 x 109/L
Remission Duration	Up to 4 years, 3 months	The date of Complete Response to the date of loss of response or last follow-up.
Leukemia-free Survival	Up to 4 years, 3 months	Survival time will be estimated using the Kaplan-Meier method. The two-sided log-rank test will be used to assess the differences of time to events between groups. Time from date of treatment start until the date of first objective documentation of disease-relapse.
Survival	Up to 4 years, 3 months	Survival time will be estimated using the Kaplan-Meier method. The two-sided log-rank test will be used to assess the differences of time to events between groups.
Number of Participants With the Most Frequently Reports Grade 3 or 4 Adverse Event.	Up to 4 years, 3 months	The most frequently reported adverse events will be determined by the Principal Investigator. The number of participants who experienced the most frequent grade 3 or 4 adverse events will be reported.

Countries

United States

Participant flow

Recruitment details

Recruitment Period: April 2014 to July 2018

Participants by arm

Arm	Count
Arm I (Guadecitabine) x 5 Days INDUCTION THERAPY: Patients receive guadecitabine SC on days 1-5. Courses repeat every 4-6 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR or CRp continue on to Maintenance therapy; patients not achieving CR or CRi but deriving clinical benefit may continue to Maintenance therapy at the discretion of the PI. MAINTENANCE THERAPY: Patients receive guadecitabine as in Induction therapy. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Guadecitabine: Given SC	13
Arm II (CLOSED) (Guadecitabine) x 10 Days INDUCTION THERAPY: Patients receive guadecitabine SC on days 1-10. Courses repeat every 4-6 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR or CRp continue on to Maintenance therapy; patients not achieving CR or CRi but deriving clinical benefit may continue to Maintenance therapy at the discretion of the PI. MAINTENANCE THERAPY: Patients receive guadecitabine SC on days 1-5 (days 1-10 of courses 1 and 2). Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Guadecitabine: Given SC	9
Arm III (Guadecitabine, Idarubicin) INDUCTION THERAPY: Patients receive guadecitabine SC on days 1-5 and idarubicin IV over up to 1 hour on days 1-2. Courses repeat every 4-6 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR or CRp continue on to Maintenance therapy; patients not achieving CR or CRi but deriving clinical benefit may continue to Maintenance therapy at the discretion of the PI. MAINTENANCE THERAPY: Patients receive guadecitabine SC on days 1-5 and idarubicin IV over up to 1 hour on day 1. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Guadecitabine: Given SC Idarubicin: Given IV	13
Arm IV (CLOSED) (Guadecitabine, Cladribine) INDUCTION THERPAY: Patients receive guadecitabine SC and cladribine IV over up to 1 hour on days 1-5. Courses repeat every 4-6 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR or CRp continue on to Maintenance therapy; patients not achieving CR or CRi but deriving clinical benefit may continue to Maintenance therapy at the discretion of the PI. MAINTENANCE THERAPY: Patients receive guadecitabine SC and cladribine IV over up to 1 hour on days 1-5. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Cladribine: Given IV Guadecitabine: Given SC	9
Total	44

Baseline characteristics

Characteristic	Arm II (CLOSED) (Guadecitabine) x 10 Days	Arm III (Guadecitabine, Idarubicin)	Arm IV (CLOSED) (Guadecitabine, Cladribine)	Arm I (Guadecitabine) x 5 Days	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	9 Participants	13 Participants	9 Participants	13 Participants	44 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Continuous	76 years	75 years	76 years	73 years	75 years
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	0 Participants	0 Participants	1 Participants	2 Participants
Race (NIH/OMB) White	8 Participants	13 Participants	9 Participants	11 Participants	41 Participants
Region of Enrollment United States	9 participants	13 participants	9 participants	13 participants	44 participants
Sex: Female, Male Female	4 Participants	4 Participants	2 Participants	2 Participants	12 Participants
Sex: Female, Male Male	5 Participants	9 Participants	7 Participants	11 Participants	32 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	2 / 13	1 / 9	1 / 13	2 / 9
other Total, other adverse events	13 / 13	7 / 9	13 / 13	9 / 9
serious Total, serious adverse events	9 / 13	7 / 9	10 / 13	6 / 9

Outcome results

Primary

Leukemia-free Survival

Survival time will be estimated using the Kaplan-Meier method. The two-sided log-rank test will be used to assess the differences of time to events between groups. Time from date of treatment start until the date of first objective documentation of disease-relapse.