Acute Myeloid Leukemia
Conditions
Keywords
acute myelogenous leukemia, acute myeloid leukemia, clolar, evoltra, clofarabine, untreated acute leukemia, adult acute leukemia
Brief summary
The purpose of the study is to determine if treatment of older patients indicated with untreated Acute Myeloid Leukemia (AML) who are not considered to be suitable for intensive chemotherapy, can effectively be treated with Clofarabine.
Detailed description
Note: This clinical trial was conducted by Bioenvision Ltd. Bioenvision Ltd. was acquired by Genzyme Corporation Oct 2007.
Interventions
DRUGclofarabine
Sponsors
Bioenvision
Genzyme, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provide signed, written informed consent * Have untreated AML according to World Health Organization (WHO) classification * Male or post-menopausal female ≥ 65 years of age * Unsuitable for intensive chemotherapy * Be able to comply with study procedures and follow-up examination * Male patient who are fertile agree to use and effective barrier method of birth control to avoid pregnancies * Have adequate liver and renal function as indicated by certain laboratory values
Exclusion criteria
* Received previous treatment with clofarabine * Are receiving other chemotherapy or corticosteroids (low-dose corticosteroid for pre-medication purposes are allowed) * Have received prior treatment for leukemia. Growth factor, cytokine support, leukopheresis or hydroxyurea will be allowed but must be discontinued at least 24 hours prior to start of treatment with clofarabine * Have a psychiatric disorder that would interfere with consent, study participation, or follow-up * Have an active, uncontrolled systemic infection * Are currently participating in other investigational drug studies or having received other investigational drugs within the previous 30 days * Have symptomatic central nervous system (CNS) involvement * Blast transformation of chronic myeloid leukemia or acute promyelocytic leukemia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | At month 20 | ORR rate was defined as the sum of the number of participants in the study population with complete remission (CR), complete remission with incomplete blood count recovery (CRi), or partial remission (PR) divided by the total number of participants in the study population. ORR rate was determined by assessment of morphology and blast count from bone marrow aspirates and peripheral blood performed prior to first dose and at the end of clofarabine treatment. The ORR was determined at the end of each cycle of clofarabine, and assessed using the participant's best response to clofarabine treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Complete Remission | From 20 months up to 48 months | Duration was calculated by Kaplan- Meier estimates |
| Rate of Response (Complete, Complete With Incomplete Blood Count Recovery, Partial) | At month 20 | Response was determined by assessment of morphology and blast count from bone marrow aspirates and peripheral blood performed prior to first dose and at the end of clofarabine treatment. Response was determined at the end of each cycle of clofarabine, and assessed using the participant's best response to clofarabine treatment. |
| Duration of Overall Response | From 20 months up to 48 months | Duration was calculated by Kaplan-Meier estimates |
| Overall Survival | From 20 months up to 48 months | Calculated by Kaplan-Meier estimates |
Countries
Ireland, Italy, United Kingdom
Participant flow
Recruitment details
Participants were entered into the study between 14 Jun 2004 and 14 Nov 2005. Participants were recruited from 14 of a total of 17 registered centres located in the United Kingdom (UK), Ireland and Italy. Relapse and survival data follow-up cut-off was extended to 23 May 2008.
Pre-assignment details
A total of 69 participants were screened and enrolled. A total of 66 participants received study drug and are included in the reported results.
Participants by arm
| Arm | Count |
|---|---|
| Clofarabine Clofarabine 30 mg/m\^2/day intravenously over 1 hour for 5 days every 28 to 42 days (one cycle), then 20mg/m\^2/day intravenously over 1 hour for 5 days every 29 to 43 days for the second and subsequent cycles, up to a maximum of 3 cycles. | 66 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 2 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Clofarabine |
|---|---|
| Age, Continuous | 71.5 years STANDARD_DEVIATION 4.65 |
| Cytogenetics (1998) Adverse | 19 participants |
| Cytogenetics (1998) Favourable | 0 participants |
| Cytogenetics (1998) Intermediate | 43 participants |
| Cytogenetics (1998) Missing/Unknown | 4 participants |
| Cytogenetics (2001) Adverse | 14 participants |
| Cytogenetics (2001) Favourable | 0 participants |
| Cytogenetics (2001) Intermediate | 48 participants |
| Cytogenetics (2001) Missing/Unknown | 4 participants |
| Glomerular Filtration Rate (mL/min/1.73m^2) <=50 | 15 participants |
| Glomerular Filtration Rate (mL/min/1.73m^2) >50 | 51 participants |
| Karnofsky Performance Status 100% | 8 participants |
| Karnofsky Performance Status 20% | 2 participants |
| Karnofsky Performance Status 50% | 5 participants |
| Karnofsky Performance Status 60% | 2 participants |
| Karnofsky Performance Status 70% | 9 participants |
| Karnofsky Performance Status 80% | 24 participants |
| Karnofsky Performance Status 90% | 13 participants |
| Karnofsky Performance Status Missing | 3 participants |
| Number of Co-morbidities 0 | 17 participants |
| Number of Co-morbidities 1 | 23 participants |
| Number of Co-morbidities >1 | 26 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 66 Participants |
| Region of Enrollment Ireland | 3 participants |
| Region of Enrollment Italy | 8 participants |
| Region of Enrollment United Kingdom | 55 participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 33 Participants |
| Type of Acute Myeloid Leukemia (AML) De Novo | 48 participants |
| Type of Acute Myeloid Leukemia (AML) Missing/Unknown | 2 participants |
| Type of Acute Myeloid Leukemia (AML) Secondary | 16 participants |
| White Blood Cell Count (10^9/L) >=100 | 3 participants |
| White Blood Cell Count (10^9/L) <25 | 57 participants |
| White Blood Cell Count (10^9/L) 25-99.9 | 6 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 66 / 66 |
| serious Total, serious adverse events | 40 / 66 |
Outcome results
Primary
Overall Response Rate (ORR)
ORR rate was defined as the sum of the number of participants in the study population with complete remission (CR), complete remission with incomplete blood count recovery (CRi), or partial remission (PR) divided by the total number of participants in the study population. ORR rate was determined by assessment of morphology and blast count from bone marrow aspirates and peripheral blood performed prior to first dose and at the end of clofarabine treatment. The ORR was determined at the end of each cycle of clofarabine, and assessed using the participant's best response to clofarabine treatment.
Time frame: At month 20
Population: The efficacy analysis was performed on the primary analysis population, the Full Analysis Set population, which consisted of all participants with a diagnosis of AML confirmed by the Investigator who received at least one dose (partial or complete) of clofarabine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clofarabine | Overall Response Rate (ORR) | 48 percentage of participants |
Secondary
Duration of Complete Remission
Duration was calculated by Kaplan- Meier estimates
Time frame: From 20 months up to 48 months
Population: The analysis were performed on the primary analysis population, the Full Analysis Set population. Defined as the median duration of participants who achieved CR+CRi only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clofarabine | Duration of Complete Remission | 63 days |
Secondary
Duration of Overall Response
Duration was calculated by Kaplan-Meier estimates
Time frame: From 20 months up to 48 months
Population: The analysis were performed on the primary analysis population, the Full Analysis Set population. Defined as the median duration of overall response (CR+CRi+PR) in participants who achieved CR, CRi or PR only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clofarabine | Duration of Overall Response | 62 days |
Secondary
Overall Survival
Calculated by Kaplan-Meier estimates
Time frame: From 20 months up to 48 months
Population: The efficacy analyses were performed on the primary analysis population, the Full Analysis Set population, which consisted of all participants with a diagnosis of AML confirmed by the Investigator who received at least one dose (partial or complete) of clofarabine.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clofarabine | Overall Survival | 173 days |
Secondary
Rate of Response (Complete, Complete With Incomplete Blood Count Recovery, Partial)
Response was determined by assessment of morphology and blast count from bone marrow aspirates and peripheral blood performed prior to first dose and at the end of clofarabine treatment. Response was determined at the end of each cycle of clofarabine, and assessed using the participant's best response to clofarabine treatment.
Time frame: At month 20
Population: The efficacy analyses were performed on the primary analysis population, the Full Analysis Set population, which consisted of all participants with a diagnosis of AML confirmed by the Investigator who received at least one dose (partial or complete) of clofarabine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clofarabine | Rate of Response (Complete, Complete With Incomplete Blood Count Recovery, Partial) | Complete response | 21 percent of participants |
| Clofarabine | Rate of Response (Complete, Complete With Incomplete Blood Count Recovery, Partial) | Complete with incomplete blood count recovery | 23 percent of participants |
| Clofarabine | Rate of Response (Complete, Complete With Incomplete Blood Count Recovery, Partial) | Partial response | 5 percent of participants |