Acute Myeloid Leukemia
Conditions
Brief summary
The objective is to treat elderly AML and MDS patients with sapacitabine.
Detailed description
The main objective of this study is to learn which sapacitabine treatment is more likely to keep the cancer in check for at least one year in AML patients who are at least 70 years of age or older and in MDS patients who are at least 60 years of age.
Interventions
DRUGSapacitabine, Arm H
300 mg q.d. x 7 consecutive days every 4 weeks
DRUGSapacitabine, Arm A
200 mg b.i.d. x 7 days every 3-4 weeks
DRUGSapacitabine, Arm B
300 mg b.i.d. x 7 days every 3 - 4 weeks
DRUGSapacitabine, Arm C
400 mg b.i.d. x 3 days/week x 2 weeks every 3 - 4 weeks
DRUGSapacitabine, Arm D
200 mg b.i.d. x 7 consecutive days every 4 weeks
DRUGsapacitabine, Arm E
300 mg q.d. x 7 consecutive days every 4 weeks
DRUGsapacitabine, Arm F
300 mg b.i.d. x 3 consecutive days per week for 2 weeks every 4 weeks
DRUGSapacitabine, Arm G
200 mg b.i.d. x 7 consecutive days every 4 weeks
DRUGSapacitabine, Arm I
100 mg q.d. x 5 consecutive days per week for 2 weeks every 4 weeks
Sponsors
Cyclacel Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A histologically or pathologically confirmed diagnosis of AML based on WHO classification which is previously untreated by systemic therapy or is in first relapse after achieving a complete remission to initial induction, consolidation and/or maintenance therapy or MDS with IPSS scores of intermediate -2 or higher risk risk which has been previously treated with hypomethylating agents * Age 70 years or older for AML and 60 years or older for MDS * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Adequate renal function defined as serum creatinine equal to or less than 1.5 x upper limit of normal (ULN) * Adequate liver function defined as total bilirubin or direct bilirubin equal to or less than 1.5 x ULN; alanine aminotransferase (ALT or SGPT) equal to or less than 2.5 x ULN (5 x ULN if tumor has affected the liver) * Life expectancy reasonably adequate for evaluating the treatment effect * Patient must be able to swallow capsules * Patients must be at least 2 weeks from prior systemic therapy, radiation therapy, major surgery, or other investigational therapy, and have recovered from clinically significant toxicities of these prior treatments * All men and women of reproductive potential must agree to practice effective contraception for 4 weeks prior to study entry, during the entire study period and for one month after the study unless documentation of infertility exists * Ability to understand and willingness to sign the informed consent form
Exclusion criteria
* AML is of the sub-type of acute promyelocytic leukemia * Having received more than one induction systemic therapy for AML or having received a standard dose or high dose ara-C containing regimen for MDS * Patients with known central nervous system (CNS) involvement by leukemia * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, active cancer(s) other than AML, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients receiving intravenous antibiotics for infections that are under control may be included in this study * Known to be HIV-positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival | up to 12 months from date of randomization | Percentage of patients alive for one year measured from the date of randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CR and CRp | From date of randomization until study withdrawal or death assessed up to 6 months | Complete remission and complete remission without blood count recovery, transfusion requirements, hospitalized days and safety |
Countries
United States
Participant flow
Pre-assignment details
Arms D through I were terminated prematurely because of financial restrictions. Accordingly the company made the determination of the dosing schedule which was used in the subsequent Phase 3 study based on the results of Arms A through C.
Participants by arm
| Arm | Count |
|---|---|
| A Sapacitabine Sapacitabine, Arm A: 200 mg b.i.d. x 7 days every 3-4 weeks | 40 |
| B Sapacitabine Sapacitabine, Arm B: 300 mg b.i.d. x 7 days every 3 - 4 weeks | 20 |
| C Sapacitabine Sapacitabine, Arm C: 400 mg b.i.d. x 3 days/week x 2 weeks every 3 - 4 weeks | 45 |
| Total | 105 |
Baseline characteristics
| Characteristic | A Sapacitabine | B Sapacitabine | C Sapacitabine | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 40 Participants | 20 Participants | 45 Participants | 105 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Patients aged 70 years or higher | 40 Participants | 20 Participants | 45 Participants | 105 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Caucasian | 37 Participants | 19 Participants | 38 Participants | 94 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 0 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Female | 17 Participants | 7 Participants | 20 Participants | 44 Participants |
| Sex: Female, Male Male | 23 Participants | 13 Participants | 25 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 40 | 6 / 20 | 4 / 45 |
| other Total, other adverse events | 40 / 40 | 20 / 20 | 45 / 45 |
| serious Total, serious adverse events | 40 / 40 | 20 / 20 | 45 / 45 |
Outcome results
Primary
Survival
Percentage of patients alive for one year measured from the date of randomization
Time frame: up to 12 months from date of randomization
Population: Arms D through I were terminated prematurely because of financial restrictions. Accordingly the company made the determination of the dosing schedule which was used in the subsequent Phase 3 study based on the results of Arms A through C.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A Sapacitabine | Survival | 35 percentage of patients alive for one yea |
| B Sapacitabine | Survival | 10 percentage of patients alive for one yea |
| C Sapacitabine | Survival | 30 percentage of patients alive for one yea |
Secondary
CR and CRp
Complete remission and complete remission without blood count recovery, transfusion requirements, hospitalized days and safety
Time frame: From date of randomization until study withdrawal or death assessed up to 6 months
Population: Arms D through I were terminated prematurely because of financial restrictions. Accordingly the company made the determination of the dosing schedule which was used in the subsequent Phase 3 study based on the results of Arms A through C.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A Sapacitabine | CR and CRp | 6 Participants |
| B Sapacitabine | CR and CRp | 2 Participants |
| C Sapacitabine | CR and CRp | 8 Participants |