Acute Myelogenous Leukemia, Chronic Myelogenous Leukemia, Myelodysplastic Syndromes
Conditions
Keywords
AML, MDS, CML, Relapsed, Refractory, Chemo treatment, Clofarabine, Cytarabine, standard or poor cytogenetic risk AML, untreated high-risk (>10% blasts) MDS, CML in accelerated phase or blast crisis, Elderly AML patients with risk of anthracycline toxicity
Brief summary
The purpose of this trial is to to determine the safety and effectiveness of therapeutic combination - Clofarabine and Cytarabine for the treatment of AML and MDS.
Detailed description
Previous studies of Clofarabine and Cytarabine combination treatment in adult AML and MDS patients showed promising results. This study is done to confirm the findings from previous studies. Primary objective is to determine the overall response rate (complete response \[CR\] plus partial response \[PR\]); secondary objective of this study is to characterize and quantify the toxicity profile associated with clofarabine plus cytarabine treatment. A maximum of 35 patients will be treated on this study. They will receive 5 consecutive days of clofarabine intra venous infusion (IVI) followed 4 hours later by cytarabine IVI.Patients will receive up to a maximum of 4 cycles of study treatment. Next cycle will start approximately 4 weeks after Day 1 of previous cycle.No other investigational or commercial agents including chemotherapy, radiotherapy, or immunotherapy may be administered to patients enrolled in this study with the intention of treating the underlying malignancy Patients will remain on study, and be monitored until 4 months have elapsed from the beginning date of their last cycle of treatment.
Interventions
DRUGClofarabine and Cytarabine
Phase II Trial of Clofarabine and Cytarabine in Relapsed Standard-Risk AML and Untreated High-Risk MDS in Adult Patients, and Untreated AML in selected Elderly Patients at high risk of anthracycline toxicity
Sponsors
Baylor Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Adult patients who are at least 18 years old with histologically confirmed disease as follows: * Standard or poor cytogenetic risk acute myelogenous leukemia (AML) according to the Southwestern Oncology Group (SWOG) criteria in first relapse or primary refractory status * Untreated high-risk myelodysplastic syndrome (MDS) defined as \>10% blasts * Chronic myelogenous leukemia (CML) in accelerated phase or blast crisis failing imatinib therapy. * Selected elderly patients with untreated AML who are at high risk of anthracycline toxicity. Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or * Laboratory values obtained less than or equal to 7 days prior to receiving study treatment: * Total bilirubin \< 2.0 mg/dL unless elevated due to hemolysis * Aspartate transaminase (AST)/alanine transaminase (ALT) less than or equal to 5 × upper limit of normal (ULN) * Serum creatinine \< 2.0 mg/dL * Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. * Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment. * Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
Exclusion criteria
* Patients with FAB M3 unless relapsed after treatment with ATRA and arsenic trioxide. * Patients eligible to receive curative allogeneic transplant as determined by performance status, organ function, availability of a matched donor, etc. * Current concomitant chemotherapy, radiation therapy, or immunotherapy. * Use of investigational agents within 30 days or any anticancer therapy within 3 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy. * Active heart disease including myocardial infarction within the preceding 3 months. * History of severe coronary artery disease, arrhythmias other than atrial flutter or fibrillation requiring medication, or uncontrolled congestive heart failure * Dyspnea at rest or with minimal exertion. * Patients with an active, uncontrolled systemic infection considered to be opportunistic, life-threatening, or clinically significant at the time of treatment or with a known or suspected fungal infection (ie, patients on parenteral antifungal therapy). * Pregnant or lactating patients. * Prior enrollment in this trial. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Complete Response [CR] Plus Partial Response [PR]) of Clofarabine Plus Cytarabine in Patients With Relapsed/Refractory AML, Untreated MDS, CML in Blast Phase, or in Selected Untreated Patients With High Risk of Anthracycline Toxicity | Proportion of confirmed responses was estimated by the number of patients who achieved a CR or PR, defined as two consecutive evaluations at least 4 weeks apart, divided by the number of eligible participants in the study. | Based on International working group for diagnosis, standardization of response criteria, and treatment outcomes for reporting standards for therapeutic trials in Acute myeloid Leukemia: Complete Response (CR) was defined as normalization of marrow blasts (\< 5%), recovery of normal heamtopoiesis (absolute neutrophil count \>1 X 10\^9/l, platelet count ≥100 X10\^9/l, and absence of peripheral blood blasts, independent of transfusions and growth factor support. Partial response was defined as blood count recovery as for complete response with the exception of leukemic marrow blasts in the range of 6%-25% or a ≥50% decrease in bone marrow blasts. Treatment failure was defined as a \<25% change in marrow blasts within 30 days of starting therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Had an Adverse Event While on Treatment With Clofarabine Plus Cytarabine | Up to five months (includes follow up period of 30 days) from the day patient received their first dose of study drug | Patients will be monitored clinically and diagnostically using measures including blood test, bone marrow aspiration and MUGA. Toxicity assessment every week using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be performed. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited after the initial IRB approval in september 2004 at Baylor University Medical Center. Enrollment was closed in october 2006. The study was completed Including follow up in February 2007.
Participants by arm
| Arm | Count |
|---|---|
| Clofarabine and Cytarabine Clofarabine 40 mg/m2 IV infusion over 1 hour for 5 days; Cytarabine 1000 mg/m2 IV infusion 4 hours post clofarabine IVI. | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Clofarabine and Cytarabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 20 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age Continuous | 64 years STANDARD_DEVIATION 21 |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 30 |
| serious Total, serious adverse events | 30 / 30 |
Outcome results
Primary
Response Rate (Complete Response [CR] Plus Partial Response [PR]) of Clofarabine Plus Cytarabine in Patients With Relapsed/Refractory AML, Untreated MDS, CML in Blast Phase, or in Selected Untreated Patients With High Risk of Anthracycline Toxicity
Based on International working group for diagnosis, standardization of response criteria, and treatment outcomes for reporting standards for therapeutic trials in Acute myeloid Leukemia: Complete Response (CR) was defined as normalization of marrow blasts (\< 5%), recovery of normal heamtopoiesis (absolute neutrophil count \>1 X 10\^9/l, platelet count ≥100 X10\^9/l, and absence of peripheral blood blasts, independent of transfusions and growth factor support. Partial response was defined as blood count recovery as for complete response with the exception of leukemic marrow blasts in the range of 6%-25% or a ≥50% decrease in bone marrow blasts. Treatment failure was defined as a \<25% change in marrow blasts within 30 days of starting therapy
Time frame: Proportion of confirmed responses was estimated by the number of patients who achieved a CR or PR, defined as two consecutive evaluations at least 4 weeks apart, divided by the number of eligible participants in the study.
Population: Intent to Treat analysis; per eligible participants enrolled in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clofarabine Plus Cytarabine | Response Rate (Complete Response [CR] Plus Partial Response [PR]) of Clofarabine Plus Cytarabine in Patients With Relapsed/Refractory AML, Untreated MDS, CML in Blast Phase, or in Selected Untreated Patients With High Risk of Anthracycline Toxicity | Not Responding | 8 participants |
| Clofarabine Plus Cytarabine | Response Rate (Complete Response [CR] Plus Partial Response [PR]) of Clofarabine Plus Cytarabine in Patients With Relapsed/Refractory AML, Untreated MDS, CML in Blast Phase, or in Selected Untreated Patients With High Risk of Anthracycline Toxicity | Not evaluable | 6 participants |
| Clofarabine Plus Cytarabine | Response Rate (Complete Response [CR] Plus Partial Response [PR]) of Clofarabine Plus Cytarabine in Patients With Relapsed/Refractory AML, Untreated MDS, CML in Blast Phase, or in Selected Untreated Patients With High Risk of Anthracycline Toxicity | Overall Response Rate | 16 participants |
| Clofarabine Plus Cytarabine | Response Rate (Complete Response [CR] Plus Partial Response [PR]) of Clofarabine Plus Cytarabine in Patients With Relapsed/Refractory AML, Untreated MDS, CML in Blast Phase, or in Selected Untreated Patients With High Risk of Anthracycline Toxicity | Complete Response | 14 participants |
| Clofarabine Plus Cytarabine | Response Rate (Complete Response [CR] Plus Partial Response [PR]) of Clofarabine Plus Cytarabine in Patients With Relapsed/Refractory AML, Untreated MDS, CML in Blast Phase, or in Selected Untreated Patients With High Risk of Anthracycline Toxicity | Partial Response | 2 participants |
Secondary
Number of Participants Who Had an Adverse Event While on Treatment With Clofarabine Plus Cytarabine
Patients will be monitored clinically and diagnostically using measures including blood test, bone marrow aspiration and MUGA. Toxicity assessment every week using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be performed.
Time frame: Up to five months (includes follow up period of 30 days) from the day patient received their first dose of study drug
Population: Intention To Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clofarabine Plus Cytarabine | Number of Participants Who Had an Adverse Event While on Treatment With Clofarabine Plus Cytarabine | 30 participants; with adverse events |