CompletedNCT00602225Updated Mar 9, 2018Results posted

Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1/2 interventional study of clofarabine and cytarabine in Acute Myeloid Leukemia, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities and Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), sponsored by University of Washington. Completed at 1 site in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2018-03-09.

Sponsored by University of Washington · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 50
Allocation: Not applicable
Ages: 18 Years to 70 Years
Sex: All

Study summary

RATIONALE: Drugs used in chemotherapy, such as clofarabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Colony stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy.

PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine to see how well it works when given together with cytarabine and G-CSF in treating patients with relapsed or refractory acute myeloid leukemia

Read the detailed description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of clofarabine, and the dose-limiting toxicities of the combination of clofarabine and cytarabine with G-CSF priming, in the treatment of patients with relapsed or refractory AML.

SECONDARY OBJECTIVES:

I. To determine the hematological and non-hematological side effect profile of the combination of clofarabine, cytarabine, and G-CSF.

II. To determine the efficacy of clofarabine in combination with cytarabine and G-CSF priming in the treatment of patients with relapsed or refractory AML.

III. To determine the disease-free and overall survival after therapy with clofarabine, cytarabine, and G-CSF for relapsed or refractory AML.

OUTLINE: This is a dose escalation study of clofarabine.

PART I:

INDUCTION THERAPY: Patients receive clofarabine IV over 1 hour and cytarabine IV over 2 hours on days 1-5, and filgrastim (G-CSF) subcutaneously once daily beginning 24 hours prior to chemotherapy and continuing until blood count recover. Patients with residual leukemia (>= 5% blasts by morphology) at day 14 and if blast remain > 5% by day 21 receive a second course of induction therapy.

CONSOLIDATION THERAPY: Patients receive clofarabine, cytarabine, and G-CSF as in induction therapy. Patients may receive a second course of consolidation therapy depending on response and whether additional therapy (e.g., stem cell transplant or donor lymphocyte infusion) is planned.

PARTS II and III:

Patients receive induction therapy and consolidation therapy as in part 1.

After completion of study treatment, patients are followed every 3 months for 2 years and then annually for 3 years.

Conditions studied

Acute Myeloid Leukemia
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Acute Promyelocytic Leukemia (M3)
Recurrent Adult Acute Myeloid Leukemia

Browse trials for

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 50 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

University of Washington is the lead sponsor of 1,397 studies on the registry; 225 are open to participants now.

Of its 154 completed or terminated interventional studies of FDA-regulated products, 132 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 70 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

ECOG performance status 0-2
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 be willing to use an effective contraceptive method during the study and for a minimum of 6 months after study treatment
Serum Total or Direct bilirubin =\< 1.5 times upper limit of normal (ULN)
Aspartate transaminase (AST)/alanine transaminase (ALT) =\< 2.5 times ULN
Diagnosis of acute myeloid leukemia by WHO criteria, either relapsed or refractory; acute promyelocytic leukemia [acute promyelocytic leukemia with t(15;17)(q22;q12) and variants] would be eligible only after failure of a regimen containing arsenic trioxide
Serum creatinine =\< 1.0 mg/dL; if serum creatinine > 1.0 mg/dl, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m\^2
Alkaline phosphatase =\< 2.5 times ULN

Exclusion criteria

Exclusion Criteria:

Use of investigational agents within 30 days or initiation of any other anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea, and intrathecal therapy for leukemic meningitis
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
Have any other severe concurrent disease, history of serious organ dysfunction, or disease involving the heart, kidney, liver (including symptomatic hepatitis, veno-occlusive disease, or hepatic graft-versus-host disease [for acute >= grade 2]), or other organ system dysfunction
No concomitant cytotoxic therapy or investigational therapy is allowed during the study with the exception of intrathecal therapy for leukemic meningitis; intrathecal therapy must not be given during or within 24 hours of any 5 day Clofarabine/Cytarabine treatment period
To the extent possible, use of nephrotoxic (e.g., vancomycin, amphotericin B, etc) and hepatotoxic (e.g., voriconazole, cyclosporine, etc) agents is to be avoided during clofarabine; use of alternative medications (e.g., herbal or botanical for anticancer purposes) is not permitted during the entire study period
Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol
More than two failed induction attempts for initial diagnosis or current relapse; for patients enrolled under part III of the protocol, patients must be at first salvage after relapse less than one year from complete remission, or salvage after initial induction chemotherapy
Allogeneic transplant recipients on immunosuppression or on treatment for GVHD

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 50 participants (actual)

Study arms

Experimental
Arm I
See Detailed Description
Drug: clofarabine · Drug: cytarabine · Biological: filgrastim

Interventions

Drugclofarabine
Given IV
Also known as: CAFdA, Clofarex, Clolar
Drugcytarabine
Given IV
Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Biologicalfilgrastim
Given subcutaneously
Also known as: G-CSF, Neupogen

What researchers measure

Primary outcomes

Maximum Tolerated Dose of Clofarabine
Time frame: 45 days after the last dose of clofarabine
Dose-limiting Toxicity as Assessed by NCI CTCAE v3.0
Time frame: 45 days after the last dose of clofarabine
Response Rates by Cytogenetic Risk Category
Number of participants who achieved Complete Remission (less than 5% blasts in the marrow and count recovery of Absolute Neutrophil Count to 1,000/microL and Platelet Count to 100,000/microL) under each cytogenetic risk category.
Time frame: 45 days after the last dose of clofarabine
Response Rates by Cytogenetic Risk Category and Clofarabine Dose
Number of participants under each Cytogenetic Risk Category and Clofarabine dose who achieve CR (Complete Remission = less than 5% blasts in the marrow and count recovery of Absolute Neutrophil Count to 1,000/microL and Platelet Count to 100,000/microL) or CRp (Complete Remission, but with a platelet count of less than 100,000/microL).
Time frame: 45 days after the last dose of clofarabine
Response Rates by Duration First Complete Remission (CR1)
Number of participants whose first Complete Remission lasted 0, 1-6, 6-12, or greater than 12 months. Only those participant who had a first CR are included in this data.
Time frame: 45 days after the last dose of clofarabine
Response Rates by Salvage Number
Number of participants in each Salvage number category who achieved a Complete Remission. Salvage number refers to whether treatment with GCLAC on this study was the pariticipant's first salvage regimen (1), second salvage regimen (2), or third or greater salvage regimen (3 or greater).
Time frame: 45 days after the last dose of clofarabine

Secondary outcomes

Hematologic and Non-hematologic Side Effect Profile
Time frame: 45 days after the last dose of clofarabine
Efficacy
Number of Patients Surviving at Five Years
Time frame: At five years after the last dose of clofarabine
Disease-free Survival
Number of participants who survived and were disease-free at 5 years
Time frame: At five years after the last dose of clofarabine
Overall Survival
Time frame: At five years after the last dose of clofarabine

Results

Posted Sep 8, 2017

Participant flow

Participant flow — Overall Study
Milestone	Arm I: Filgrastim + Clofarabine + Cytarabine (GCLAC)
Started	50
Completed	50
Not completed	0

Outcome measures

PrimaryMaximum Tolerated Dose of Clofarabine

Time frame:: 45 days after the last dose of clofarabine
Reported as:: Number · mg/m^2 of clofarabine

Maximum Tolerated Dose of Clofarabine
mg/m^2 of clofarabine	Arm I: Filgrastim + Clofarabine + Cytarabine (GCLAC)
Maximum Tolerated Dose of Clofarabine	25

PrimaryDose-limiting Toxicity as Assessed by NCI CTCAE v3.0

Time frame:: 45 days after the last dose of clofarabine
Reported as:: Count of participants · Participants

Dose-limiting Toxicity as Assessed by NCI CTCAE v3.0
Participants	Arm I: Filgrastim + Clofarabine + Cytarabine (GCLAC)
Dose-limiting Toxicity as Assessed by NCI CTCAE v3.0	2

PrimaryResponse Rates by Cytogenetic Risk Category

Number of participants who achieved Complete Remission (less than 5% blasts in the marrow and count recovery of Absolute Neutrophil Count to 1,000/microL and Platelet Count to 100,000/microL) under each cytogenetic risk category.

Time frame:: 45 days after the last dose of clofarabine
Reported as:: Count of participants · Participants

Response Rates by Cytogenetic Risk Category
Participants	Arm I
Favorable risk Complete Remission	3
Intermediate risk Complete remission	10
Unfavorable risk Complete remission	9

PrimaryResponse Rates by Cytogenetic Risk Category and Clofarabine Dose

Number of participants under each Cytogenetic Risk Category and Clofarabine dose who achieve CR (Complete Remission = less than 5% blasts in the marrow and count recovery of Absolute Neutrophil Count to 1,000/microL and Platelet Count to 100,000/microL) or CRp (Complete Remission, but with a platelet count of less than 100,000/microL).

Time frame:: 45 days after the last dose of clofarabine
Reported as:: Count of participants · Participants

Response Rates by Cytogenetic Risk Category and Clofarabine Dose
Participants	Arm I
Favorable Risk + 25 mg/m^2 achieve CR	2
Intermediate Risk + 15 mg/m^2 achieve CR	2
Intermediate Risk + 20 mg/m^2 achieve CR	3
Intermediate Risk + 25 mg/m^2 achieve CR	5
Intermediate Risk + 25 mg/m^2 achieve CRp	4
Unfavorable Risk + 15 mg/m^2 achieve CR	2
Unfavorable Risk + 20 mg/m^2 achieve CR	1
Unfavorable Risk + 25 mg/m^2 achieve CR	6
Unfavorable Risk + 25 mg/mg^2 achieve CRp	3

PrimaryResponse Rates by Duration First Complete Remission (CR1)

Number of participants whose first Complete Remission lasted 0, 1-6, 6-12, or greater than 12 months. Only those participant who had a first CR are included in this data.

Time frame:: 45 days after the last dose of clofarabine
Reported as:: Count of participants · Participants

Response Rates by Duration First Complete Remission (CR1)
Participants	Arm I
Duration CR1 (months): 0	12
Duration CR1 (months): 1-6	4
Duration CR1 (months): 6-12	2
Duration CR1 (months): greater than 12	3

PrimaryResponse Rates by Salvage Number

Number of participants in each Salvage number category who achieved a Complete Remission. Salvage number refers to whether treatment with GCLAC on this study was the pariticipant's first salvage regimen (1), second salvage regimen (2), or third or greater salvage regimen (3 or greater).

Time frame:: 45 days after the last dose of clofarabine
Reported as:: Count of participants · Participants

Response Rates by Salvage Number
Participants	Arm I
Salvage number 1	16
Salvage number 2	5
Salvage number 3 or greater	0

SecondaryHematologic and Non-hematologic Side Effect Profile

Time frame:: 45 days after the last dose of clofarabine

No measurements were reported for this outcome.

SecondaryEfficacy

Number of Patients Surviving at Five Years

Time frame:: At five years after the last dose of clofarabine
Reported as:: Count of participants · Participants

Efficacy
Participants	Arm I: Filgrastim + Clofarabine + Cytarabine (GCLAC)
Efficacy	12

SecondaryDisease-free Survival

Number of participants who survived and were disease-free at 5 years

Time frame:: At five years after the last dose of clofarabine
Reported as:: Count of participants · Participants

Disease-free Survival
Participants	Arm I: Filgrastim + Clofarabine + Cytarabine (GCLAC)
Disease-free Survival	11

SecondaryOverall Survival

Time frame:: At five years after the last dose of clofarabine
Reported as:: Median · months

Overall Survival
months	Arm I
Overall Survival	9 (5.2 to 13)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Arm I	—	23/50 (46%)	—

Most frequent serious events

Most frequent serious events
Event	Arm I
PulmonaryRespiratory, thoracic and mediastinal disorders	23/50
infectionInfections and infestations	20/50
Hepatic transaminasesHepatobiliary disorders	8/50
GastrointestinalGastrointestinal disorders	6/50
SkinSkin and subcutaneous tissue disorders	5/50
HyperbilirubinaemiaInvestigations	4/50
RenalRenal and urinary disorders	2/50
PainGeneral disorders	1/50
NeuropathyNervous system disorders	1/50
Tumor LysisInvestigations	1/50

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Arm I
Median	53 (19 to 69)

Sex: Female, Male
Sex: Female, Male(Participants)	Arm I
Female	14
Male	36

AML Onset: de novo
AML Onset: de novo(Participants)	Arm I
Count of participants	32

AML Onset: secondary
AML Onset: secondary(Participants)	Arm I
Count of participants	18

Relapsed
Relapsed(Participants)	Arm I
Count of participants	32

First salvage
First salvage(Participants)	Arm I
Count of participants	32

Second or greater salvage
Second or greater salvage(Participants)	Arm I
Count of participants	18

Refractory
Refractory(Participants)	Arm I
Count of participants	18

4 further baseline measures are reported on the registry.

Study locations

1 site

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington 98109, United States

References and documents

Publications

Becker PS, Kantarjian HM, Appelbaum FR, Storer B, Pierce S, Shan J, Faderl S, Estey EH. Retrospective comparison of clofarabine versus fludarabine in combination with high-dose cytarabine with or without granulocyte colony-stimulating factor as salvage therapies for acute myeloid leukemia. Haematologica. 2013 Jan;98(1):114-8. doi: 10.3324/haematol.2012.063438. Epub 2012 Jul 16. PubMed 22801963 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 9, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00602225
Lead sponsor: University of Washington
Collaborators: National Cancer Institute (NCI)
Responsible party: Pamela S Becker (Principal Investigator, University of Washington) — Principal investigator
First posted: Jan 28, 2008
Start date: Dec 2007
Primary completion: Mar 2010
Completion: Apr 2015
Results posted: Sep 8, 2017
Last update: Mar 9, 2018

Study contacts

Pamela Becker

principal investigator · Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2018. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Leukemia→

Other studies from this sponsor

University of Washington

Start the discussion