Clofarabine and Ara-C for the Treatment of Relapsed AML and Untreated MDS

• Sponsor: Baylor Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00334074
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arm: 1
• Duration (Months): 30
• Patients Per Site Per Month: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myelogenous Leukemia; Myelodysplastic Syndromes; Chronic Myelogenous Leukemia	Drug: Clofarabine and Cytarabine	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Feb 1, 2007
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clofarabine and Cytarabine Five consecutive days of clofarabine 40 mg/m^2 IVI over 1 hour followed 4 hours later by cytarabine 1000 mg/m^2 IVI over 2 hours	Drug: Clofarabine 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; Other Names: Clofarabine: CAFdA; Cl-F-ara-A Cytarabine: Ara-C

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baylor University Medical Center	Dallas	Texas	United States	75246

Sponsors and Collaborators

• Baylor Research Institute

Investigators

• Principal Investigator: Edward Agura, MD, Baylor University Medical Center - Director Blood and Marrow Transplantation Services

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Baylor Research Institute
• ClinicalTrials.gov Identifier: NCT00334074
• Other Study ID Numbers: 004-145; 004-145
• First Posted: Jun 6, 2006
• Last Update Posted: Jul 17, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Baylor Research Institute: 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
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Cytarabine; Clofarabine

Study Results

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.

Arm/Group Title	Clofarabine and Cytarabine
Arm/Group Description	5 consecutive days of Clofarabine 40 mg/m^2 intravenous infusion over 1 hour followed 4 hours later by cytarabine 1000mg/m^2 intravenous infusion over 2 hours.Next cycle will start approximately 4 weeks after Day 1 of previous cycle. Patients will receive a maximum of 4 cycles of study treatment.
Period Title: Overall Study
STARTED	30
COMPLETED	30
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Clofarabine and Cytarabine
Arm/Group Description	Clofarabine 40 mg/m2 IV infusion over 1 hour for 5 days; Cytarabine 1000 mg/m2 IV infusion 4 hours post clofarabine IVI.
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 33.3%
>=65 years	20 66.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64 (21)
Sex: Female, Male (Count of Participants)
Female	13 43.3%
Male	17 56.7%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	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
Description	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.

Outcome Measure Data

Analysis Population Description

Intent to Treat analysis; per eligible participants enrolled in the study.

Arm/Group Title	Clofarabine Plus Cytarabine
Arm/Group Description	Clofarabine 40 mg/m2 IV infusion over 1 hour for 5 days; Four hours post clofarabine infusion,Give cytarabine 1000 mg/m2 IV infusion over 2 hours.Patients will receive a maximum upto 4 cycles of study treatment.Next cycle will start approximately 4 weeks after Day 1 of previous cycle.
Measure Participants	30
Overall Response Rate	16 53.3%
Complete Response	14 46.7%
Partial Response	2 6.7%
Not Responding	8 26.7%
Not evaluable	6 20%

2. Secondary Outcome

Title	Number of Participants Who Had an Adverse Event While on Treatment With Clofarabine Plus Cytarabine
Description	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

Outcome Measure Data

Analysis Population Description

Intention To Treat

Arm/Group Title	Clofarabine and Cytarabine
Arm/Group Description	Clofarabine 40 mg/m2 IV infusion over 1 hour for 5 days; Cytarabine 1000 mg/m2 IV infusion 4 hours post clofarabine IVI.
Measure Participants	30
Number [participants; with adverse events]	30 100%

Adverse Events

Time Frame	1 year 6 months. Initial IRB approval in 9/2004. Enrollment start date - 8/2005. Study completion including follow up - Feb 2007.
Arm/Group Title	Clofarabine and Cytarabine
Arm/Group Description	Clofarabine 40 mg/m2 intravenous infusion over 1 hour for 5 days; Cytarabine 1000 mg/m2 intravenous infusion 4 hours post clofarabine IVI.
All Cause Mortality
	Clofarabine and Cytarabine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Clofarabine and Cytarabine
	Affected / at Risk (%)	# Events
Total	30/30 (100%)
Blood and lymphatic system disorders
Edema/Weight Gain	3/30 (10%)	3
Pancytopenia	24/30 (80%)	24
Platelet Allosensitization	1/30 (3.3%)	1
Thrombocytopenia	1/30 (3.3%)	1
Volume Overload	1/30 (3.3%)	1
Cardiac disorders
Atrial Fibrillation	3/30 (10%)	3
Myocardial Infarction	1/30 (3.3%)	1
Gastrointestinal disorders
Nausea	1/30 (3.3%)	1
Small Bowell Obstruction	1/30 (3.3%)	1
Perianal Abcess	1/30 (3.3%)	1
Infections and infestations
Febrile Neutropenia	2/30 (6.7%)	2
Fever	3/30 (10%)	3
Fungal Pneumonia	2/30 (6.7%)	2
Sepsis	5/30 (16.7%)	5
Staph Bacteremia	1/30 (3.3%)	1
Staph epidermitis	1/30 (3.3%)	1
Bilateral External Otitis	1/30 (3.3%)	1
Multiple System Organ Failure	6/30 (20%)	6
Investigations
Elevated LFT	1/30 (3.3%)	1
Metabolism and nutrition disorders
Hyperglycemia	1/30 (3.3%)	1
Nervous system disorders
Delirium	1/30 (3.3%)	1
Renal and urinary disorders
Renal Insufficiency / Failure	3/30 (10%)	3
Respiratory, thoracic and mediastinal disorders
Pulmonary Infiltrate	1/30 (3.3%)	1
Respiratory Failure	3/30 (10%)	3
Respiratory Distress	2/30 (6.7%)	2
Pneumonia	2/30 (6.7%)	2
Skin and subcutaneous tissue disorders
Hand and Foot Syndrome	3/30 (10%)	3
Other (Not Including Serious) Adverse Events
	Clofarabine and Cytarabine
	Affected / at Risk (%)	# Events
Total	29/30 (96.7%)
Blood and lymphatic system disorders
Edema/Weight Gain	14/30 (46.7%)	14
Gastrointestinal disorders
Diarrhea	17/30 (56.7%)	17
Nausea	12/30 (40%)	12
Infections and infestations
Fever	13/30 (43.3%)	13
Skin and subcutaneous tissue disorders
Rash	13/30 (43.3%)	13

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.