Myelodysplastic SyndromesPhase 1/2NCT00503880

Clofarabine, Cytarabine, and G-CSF in Treating Patients With Myelodysplastic Syndromes

A Phase 1/2 study testing filgrastim, clofarabine and cytarabine in people with Myelodysplastic Syndromes, run by University of Nebraska at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 19 to 120 years
Conditions the study is for: Myelodysplastic Syndromes
What is being tested?: filgrastim, clofarabine and cytarabine
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2 participants
Where: 1 siteUnited States
Study dates: 7 May 2007to 13 Oct 2009
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 19 to 120 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Confirmed pathologic diagnosis of myelodysplastic syndromes
International Prognostic Scoring System score of intermediate-2 or high-riskFailed or progressed after 1 prior FDA-approved treatment for MDS OR refused the FDA-approved treatment
Not a candidate for intensive or standard chemotherapy or stem cell transplantation, as determined by the treating physician
ECOG performance status 0-2
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST or ALT ≤ 3 times ULN
Creatinine < 2.0 mg/dL
Fertile patients must use effective contraception

Who cannot join

Not pregnant or nursing
No comorbidity or condition that, in the opinion of the investigator, may interfere with the assessments and procedures of this protocol or that would decrease life expectancy to < 3 months
No active, serious infection not controlled by oral or IV antibiotics

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Nebraska Medical Center
Omaha, Nebraska, 68198

Other trials in United States

About this study

Official title: A Dose Escalation Phase I/II Study of Clofarabine Plus Cytarabine With Growth Factor Priming in Patients Who Are Not Felt to be Candidates for More Aggressive Treatment, With Int-2 and High-Risk MDS

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 by stopping them from dividing. Colony-stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or in peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving clofarabine and cytarabine together with G-CSF may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine and to see how well it works when given together with cytarabine and G-CSF in treating patients with myelodysplastic syndromes.

Read the detailed description

OBJECTIVES:

Primary

To determine the maximum tolerated dose (MTD) of clofarabine when administered with low-dose cytarabine and filgrastim (G-CSF) in patients with intermediate-2 or high-risk myelodysplastic syndromes (MDS).
To evaluate efficacy as measured by hematologic response rates in patients who are treated with this novel combination of drugs and who are not candidates for more intensive treatment for intermediate-2 and high-risk MDS.

Secondary

To assess effects on quality of life of this patient population.
To assess the time to acute myeloid leukemia transformation or death.
To assess cytogenetic response rates.
To assess changes in flow cytometric patterns.

OUTLINE: This is a phase I, nonrandomized, dose-escalation study of clofarabine followed by a phase II study.

Phase I: Patients receive clofarabine IV over 1 hour and low-dose cytarabine subcutaneously (SC) on days 1-5. Patients also receive filgrastim (G-CSF) SC beginning 1 day prior to the start of chemotherapy and continuing through completion of chemotherapy until blood counts recover. Treatment repeats every 6 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of clofarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive clofarabine at the MTD, cytarabine, and G-CSF as in phase I.

Quality of life is assessed at baseline, prior to course 4, and after completion of study therapy.

Patients undergo bone marrow biopsy at baseline and prior to courses 3, 6, and 8 for evaluation of treatment response. Bone marrow samples are analyzed for myeloblast phenotypic expression profiles, which include the following parameters: percentage of CD34-positive myeloblasts; antigen expression density of CD13, CD34, CD45, and CD117; and aberrant myeloblast expression of CD4, CD11c, CD15, and CD56.

Conditions: Myelodysplastic Syndromes
Being tested: filgrastim, clofarabine, cytarabine, microarray analysis, biopsy
Keywords: de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes
Medical subject headings: Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

filgrastimBiological
Also called Neupogen
subcutaneously one day prior to treatment
clofarabineDrug
Also called Clolar
single IV dose over 1 hour daily for 5 days
cytarabineDrug
Also called cytosine arabinoside
subcutaneously daily for 5 days 2-4 hours following the end of the Clofarabine infusion
microarray analysisGenetic
Both standard cytogenetic testing and FISH (fluorescent in situ hybridization) are adequate to assess responses.
biopsyProcedure or surgery
bone marrow biopsy

Study groups in NCT00503880
Study group	Role	What they receive
Treatment	Experimental	G-CSF 300 μg subcutaneously to begin one day prior to treatment and continued until ANC greater than 1.0 or recovers back to the patients baseline ANC for 3 days in a row subsequent to completion of chemotherapy (SOC) Low-dose Cytarabine 10 mg/m2 subcutaneously daily starting on day 1 for the first 5 consecutive days of the treatment course 2-4 hours following the end of the clofarabine infusion. (SOC) Clofarabine starting at dose level 0. Dose-10 mg/m2 IV over 1 hour daily starting on day 1 for the first 5 consecutive days of the treatment course The G-CSF and cytarabine doses are fixed. The dose of clofarabine is initially fixed. For the subsequent cohort, the dose of clofarabine will be advanced to the next dose level. Receives: Biological: filgrastim; Drug: clofarabine; Drug: cytarabine; Genetic: microarray analysis; Procedure: biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Tolerated Dose of Clofarabine (Phase I)
Maximum Tolerated Dose (MTD) is defined to be the dose cohort below which 2 out of 6 patients experience dose limiting toxicities or the highest dose cohort, if 2 limiting toxicities are not observed at any dose cohort. These will be presented as actual rates. Dose limiting toxicity (DLT) will be defined according to oncology standards based on NCI CTC version 2 grading criteria (DLT = > grade 3 non-hematological toxicity or any > 4 hematological toxicity that persists for more than 4 weeks and in the opinion of the investigator is felt not to be due to disease).
Measured: 7 months
Presence of Hematologic Response (Phase II)
These are measured in patients with pretreatment abnormalities defined as:
Hemoglobin < 11 g/dL or transfusion dependence [erythroid- E] Platelets less than 100 x 109/L or platelet-transfusion dependence [platelet- P] Absolute neutrophil count (ANC) less than 1.0 x 109/L [neutrophil- N] Pretreatment baseline measures of cytopenias are averages of at least 2 measurements (not influenced by transfusions)- at least 1 week apart.
Measured: Following phase I, responses must last at least 8 weeks.

Secondary outcomes (4)

Assess Quality of Life
To assess effects on quality of life of this patient population (questionnaire).
Measured: 7 months
Time to Acute Myelooid Leukemia Transformation or Death.
To assess the time to acute myeloid leukemia transformation or death.
Measured: 7months
Cytogenetic Response Rates
To assess cytogenetic response rates.
Measured: 7 months
Changes in Flow of Cytometric Patterns.
To assess changes in flow cytometric patterns.
Measured: 7 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 May 200713 Oct 2009

First posted19 Jul 2007 (estimated)
Study start7 May 2007
Primary completion13 Oct 2009
Study completion13 Oct 2009

Why it stopped: Genzyme discontinued Funding

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
More trials run by University of NebraskaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 2 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00503880
Sponsor's protocol ID: 0032-07-FB
Other IDs: P30CA036727
Status last verified: Aug 2023
First submitted: 17 Jul 2007
Last updated: 18 Sep 2023
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
High Grade Myelodysplastic Syndromes
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

All Myelodysplastic Syndromes trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Dose Escalation Phase I/II Study of Clofarabine Plus Cytarabine With Growth Factor Priming in Patients Who Are Not Felt to be Candidates for More Aggressive Treatment, With Int-2 and High-Risk MDS
ClinicalTrials.gov ID: NCT00503880
Acronym / sponsor ID: 0032-07-FB
Conditions: Myelodysplastic Syndromes
Keywords: de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Genzyme discontinued Funding
Enrolment: 2 participants (actual)
Lead sponsor: University of NebraskaUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 7 May 2007 (actual)
Primary completion: 13 Oct 2009 (actual)
Study completion: 13 Oct 2009 (actual)
First posted: 19 Jul 2007 (estimated)
Results: Posted 13 Apr 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

OBJECTIVES:

Primary

To determine the maximum tolerated dose (MTD) of clofarabine when administered with low-dose cytarabine and filgrastim (G-CSF) in patients with intermediate-2 or high-risk myelodysplastic syndromes (MDS).
To evaluate efficacy as measured by hematologic response rates in patients who are treated with this novel combination of drugs and who are not candidates for more intensive treatment for intermediate-2 and high-risk MDS.

Secondary

To assess effects on quality of life of this patient population.
To assess the time to acute myeloid leukemia transformation or death.
To assess cytogenetic response rates.
To assess changes in flow cytometric patterns.

OUTLINE: This is a phase I, nonrandomized, dose-escalation study of clofarabine followed by a phase II study.

Phase I: Patients receive clofarabine IV over 1 hour and low-dose cytarabine subcutaneously (SC) on days 1-5. Patients also receive filgrastim (G-CSF) SC beginning 1 day prior to the start of chemotherapy and continuing through completion of chemotherapy until blood counts recover. Treatment repeats every 6 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.

Phase II: Patients receive clofarabine at the MTD, cytarabine, and G-CSF as in phase I.

Quality of life is assessed at baseline, prior to course 4, and after completion of study therapy.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment	Experimental	Biological: filgrastim, Drug: clofarabine, Drug: cytarabine, Genetic: microarray analysis, Procedure: biopsyG-CSF 300 μg subcutaneously to begin one day prior to treatment and continued until ANC greater than 1.0 or recovers back to the patients baseline ANC for 3 days in a row subsequent to completion of chemotherapy (SOC) Low-dose Cytarabine 10 mg/m2 subcutaneously daily starting on day 1 for the first 5 consecutive days of the treatment course 2-4 hours following the end of the clofarabine infusion. (SOC) Clofarabine starting at dose level 0. Dose-10 mg/m2 IV over 1 hour daily starting on day 1 for the first 5 consecutive days of the treatment course The G-CSF and cytarabine doses are fixed. The dose of clofarabine is initially fixed. For the subsequent cohort, the dose of clofarabine will be advanced to the next dose level.

Who may qualify

Ages: 19 to 120 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Confirmed pathologic diagnosis of myelodysplastic syndromes
International Prognostic Scoring System score of intermediate-2 or high-riskFailed or progressed after 1 prior FDA-approved treatment for MDS OR refused the FDA-approved treatment
Not a candidate for intensive or standard chemotherapy or stem cell transplantation, as determined by the treating physician
ECOG performance status 0-2
Bilirubin ≤ 1.5 times upper limit of normal (ULN)

Key exclusion criteria (3 listed)

Not pregnant or nursing
No comorbidity or condition that, in the opinion of the investigator, may interfere with the assessments and procedures of this protocol or that would decrease life expectancy to < 3 months
No active, serious infection not controlled by oral or IV antibiotics

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
filgrastimAlso: Neupogensubcutaneously one day prior to treatment	Biological	Treatment
clofarabineAlso: Clolarsingle IV dose over 1 hour daily for 5 days	Drug	Treatment
cytarabineAlso: cytosine arabinosidesubcutaneously daily for 5 days 2-4 hours following the end of the Clofarabine infusion	Drug	Treatment
microarray analysisBoth standard cytogenetic testing and FISH (fluorescent in situ hybridization) are adequate to assess responses.	Genetic	Treatment
biopsybone marrow biopsy	Procedure or surgery	Treatment

Primary outcome

Maximum Tolerated Dose of Clofarabine (Phase I)
Time frame: 7 months
Maximum Tolerated Dose (MTD) is defined to be the dose cohort below which 2 out of 6 patients experience dose limiting toxicities or the highest dose cohort, if 2 limiting toxicities are not observed at any dose cohort. These will be presented as actual rates. Dose limiting toxicity (DLT) will be defined according to oncology standards based on NCI CTC version 2 grading criteria (DLT = > grade 3 non-hematological toxicity or any > 4 hematological toxicity that persists for more than 4 weeks and in the opinion of the investigator is felt not to be due to disease).
Presence of Hematologic Response (Phase II)
Time frame: Following phase I, responses must last at least 8 weeks.
These are measured in patients with pretreatment abnormalities defined as: Hemoglobin < 11 g/dL or transfusion dependence [erythroid- E] Platelets less than 100 x 109/L or platelet-transfusion dependence [platelet- P] Absolute neutrophil count (ANC) less than 1.0 x 109/L [neutrophil- N] Pretreatment baseline measures of cytopenias are averages of at least 2 measurements (not influenced by transfusions)- at least 1 week apart.

4 secondary outcomes

Assess Quality of Life
Time frame: 7 months
Time to Acute Myelooid Leukemia Transformation or Death.
Time frame: 7months
Cytogenetic Response Rates
Time frame: 7 months
Changes in Flow of Cytometric Patterns.
Time frame: 7 months

Results and safety

Results posted to the registry on 13 Apr 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase I: Cohort #1	2	0
Phase I: Cohort #2	0	0
Phase 1: Dose Cohort #3	0	0
Phase I: Cohort #4	0	0
Phase II: Clinical Response	0	0

Primary outcome: Maximum Tolerated Dose of Clofarabine (Phase I)

Time frame: 7 months

Population analysed: Not done - Genzyme discontinued Funding

Primary outcome: Presence of Hematologic Response (Phase II)

Time frame: Following phase I, responses must last at least 8 weeks.

Population analysed: The study only enrolled 2 patients of the planned 30. The two patients enrolled did not complete the research as planned and were not evaluable. The study was closed due to lack of funding support. Data were not collected.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 6 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment	1 of 2 (50%)	2 of 2 (100%)	1 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Myelodysplastic Syndromes

RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
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RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
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Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Lori J Maness, MD principal investigator

University of Nebraska

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing filgrastim, clofarabine and cytarabine in people with Myelodysplastic Syndromes, run by University of Nebraska at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose of Clofarabine (Phase I) (time frame: 7 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00503880.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2023.