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LeukemiaPhase 1/2NCT01289457

Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI) in Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome

A Phase 1/2 study testing Clofarabine, Idarubicin and Cytarabine in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The goal of this clinical research study is to learn if the combination of clofarabine, idarubicin, and cytarabine, or the combination of fludarabine, idarubicin, and cytarabine can help control Acute myeloid leukemia (AML) and Myelodysplastic syndromes (MDS). Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Leukemia
What is being tested?
Clofarabine, Idarubicin and Cytarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
282 participants
Where
1 siteUnited States
Study dates
2 Feb 2011to 28 Jun 2017
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 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Sign an Institutional Review Board (IRB)-approved informed consent document.
  • Age 18 to 60. Patients above the age of 60 only with principal investigator (PI) approval
  • Diagnosis of newly diagnosed AML [other than acute promyelocytic leukemia (APL)] or high-risk (intermediate-2 or high by International Prostate Symptom Score (IPSS) or > 10% blasts, including CMML) MDS. Prior therapy with hydrea and the use of a single or a two day dose of cytarabine (up to 3 g/m2) for emergency use up to 24 hours prior to start of study therapy is allowed. Prior therapy for MDS or other AHD is not allowed.
  • Eastern Cooperative Oncology Group (ECOG) performance status of </= 3 at study entry.
  • Organ function as defined below (unless due to leukemia): Serum creatinine </= 3 mg/dL Total bilirubin </= 2.5 mg/dL , Alanine aminotransferase (ALT) (SGPT) </= 3 * upper limit of normal (ULN) or </= 5 * ULN if related to disease.
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days and must agree to practice acceptable contraceptive methods. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.
  • Cardiac ejection fraction >/= 40% (by either cardiac echo or multiple gated acquisition scan (MUGA) scan). Documentation of recent (</= 6 months from screening) outside reports is acceptable.

Who cannot join

  • Breast feeding females
  • Patients with uncontrolled active infections (viral, bacterial, and fungal are not eligible).
  • Patients with active secondary malignancy will not be eligible.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I/II Randomized Study of Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI) in Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome

The goal of this clinical research study is to learn if the combination of clofarabine, idarubicin, and cytarabine, or the combination of fludarabine, idarubicin, and cytarabine can help control Acute myeloid leukemia (AML) and Myelodysplastic syndromes (MDS). The safety of these study drug combinations will also be studied.

Read the detailed description

The Study Drugs:

Clofarabine is designed to interfere with the growth and development of cancer cells.

Idarubicin is designed to cause breaks in both strands of DNA (the genetic material of cells). This may cause the cancer cells to die.

Cytarabine and Fludarabine are designed to insert themselves into the DNA of cancer cells and stop the DNA from repairing itself.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 4 groups of 6 participants will be enrolled in the Phase I portion of the study. Up to 280 participants will be enrolled in Phase II.

Phase I:

If you are enrolled in the Phase I portion, the dose of clofarabine you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of clofarabine. Each new group will receive a higher dose of clofarabine than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of clofarabine is found.

All participants will receive the same dose level of idarubicin and cytarabine.

Phase II:

If you are enrolled in the Phase II portion, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups:

  • If you are in Group 1, you will receive clofarabine, idarubicin, and cytarabine. You will receive clofarabine at the highest dose that was tolerated in the Phase I portion.
  • If you are in Group 2, you will receive fludarabine, idarubicin, and cytarabine.

Study Drug Administration:

Study drug(s) will be given in what are called "cycles." Each cycle is 28 days.

Phase I:

On Days 1-5:

  • You will receive clofarabine by vein over about 1 hour.
  • You will receive cytarabine by vein over about 2 hours.
  • On Days 1-3 only, you will receive idarubicin by vein over about 30 minutes.

Phase II (Induction):

The first cycle of study drugs is called Induction. If the doctor thinks it is needed, you will have up to 2 Induction cycles.

If you are in Group 1:

On Days 1-5 of each cycle:

  • You will receive clofarabine by vein over about 1 hour.
  • You will receive cytarabine by vein over about 2 hours.
  • On Days 1-3 only, you will receive idarubicin by vein over about 30 minutes.

If you are in Group 2:

On Days 1-5 of each cycle:

  • You will receive fludarabine by vein over about 30 minutes.
  • You will receive cytarabine by vein over about 2 hours.
  • On Days 1-3 only, you will receive idarubicin by vein over about 30 minutes.

If the doctor thinks it is needed, you may receive less than 5 days of treatment in the induction cycle.

If the doctor thinks it is needed, your dose level will be reduced after Induction.

Phase II (Consolidation):

If the disease responds to the study drugs, you may receive up to 6 more cycles of study drugs. This is called Consolidation.

If you are in Group 1:

On Days 1-3 of each cycle :

  • You will receive clofarabine by vein over about 1 hour.
  • You will receive cytarabine by vein over about 2 hours.
  • After 1 to 2 hours of receiving cytarabine on Days 1-2 only, you will receive idarubicin by vein over about 30 minutes.

If you are in Group 2:

On Days 1-3 of each cycle:

  • You will receive fludarabine by vein over about 30 minutes
  • You will receive cytarabine by vein over about 2 hours.
  • After 1 to 2 hours of receiving cytarabine on Days 1-2 only, you will receive idarubicin by vein over about 30 minutes

If the cancer does not completely respond after Cycle 1, you may repeat induction (Cycle 1). If the cancer completely responds, you will begin the consolidation cycles.

If the doctor thinks it is needed, you may receive less than 3 days of treatment in the consolidation cycles.

Study Visits:

You will have a physical exam, including measurement of your vital signs before the start of each cycle. Blood (about 2 teaspoons) will be drawn for routine tests every 3-7 days.

On Day 28 of every 2-3 cycles (+/- 7 days), if the doctor thinks it is needed, you will have a bone marrow aspirate to check the status of the disease. To collect a bone marrow aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest or up to 8 total cycles. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.

Your participation on the study will be over once you have completed the long-term follow-up.

Long-Term Follow-up:

Every 3 months for 1 year after you are off study, you will be called and asked how you are feeling, about any side effects you may be having, and about any other drugs you may be taking. These calls should last about 5 minutes each.

This is an investigational study. Cytarabine and Idarubicin are FDA approved and commercially available for the treatment of AML. Fludarabine is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL). Clofarabine is FDA approved and commercially available for the treatment of acute lymphoblastic leukemia (ALL). The combination of these study drugs is investigational.

Up to 292 patients will take part in Phase I and Phase II of this study. All will be enrolled at MD Anderson.

Conditions
Leukemia
Being tested
Clofarabine, Idarubicin, Cytarabine, Fludarabine
Keywords
Acute Myelogenous Leukemia, AML, High-Risk Myelodysplastic Syndrome, MDS, Relapsed, Refractory, Clofarabine, Clofarex, Clolar, Idarubicin, Idamycin, Cytarabine, Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride
Medical subject headings
Leukemia, Leukemia, Myeloid, Acute, Recurrence

What participants receive

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

  • ClofarabineDrug

    Also called Clofarex, Clolar

    Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle.

    Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle.

  • IdarubicinDrug

    Also called Idamycin

    10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle.

  • CytarabineDrug

    Also called Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride

    1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.

  • FludarabineDrug

    Also called Fludara

    30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).

Study groups in NCT01289457
Study groupRoleWhat they receive
Clofarabine + Idarubicin + CytarabineExperimentalPhase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5.
Receives: Drug: Clofarabine; Drug: Idarubicin; Drug: Cytarabine; Drug: Fludarabine
Group 1 CIAExperimentalPhase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine Maximum Tolerated Dose (MTD) based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.
Receives: Drug: Clofarabine; Drug: Idarubicin; Drug: Cytarabine
Group 2 FLAIExperimentalPhase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.
Receives: Drug: Idarubicin; Drug: Cytarabine; Drug: Fludarabine

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of Clofarabine, Idarubicin, and Cytarabine

    MTD is highest dose level in which <2 patients of 6 develop first cycle dose limiting toxicities (DLT). Toxicity defined as any treatment-related grade 3 or greater non-hematological toxicities.

    Measured: 28 days

Secondary outcomes (3)
  1. Response Rates of Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI)

    NCI \& Myelodysplastic syndromes (MDS) International Working Group (IWG) Definitions: Complete Response (CR): Neutrophil count ≥1.0 ×10^9/L, Platelet count ≥100 ×10^9/L, Bone marrow aspirate </=5% blasts, No extramedullary leukemia; CRi: Response as in CR but platelets <100 ×10^9/L; Partial response (PR): Neutrophil count ≥ 1.0 ×10^9/L, Platelet count ≥100 ×10^9/L, ≥ 50% reduction in bone marrow blasts over baseline; Clinical benefit: In addition to IWG criteria, in AML, a decrease in bone marrow blasts to <5% is also considered clinical benefit; Stable Disease: In addition to IWG criteria and in absence any of above response criteria, stable disease considered if the bone marrow blast percent does not increase compared to pretreatment level; Relapse: Increase of bone marrow blasts to >10% after initial response. Response assessed Day 28 of every 2-3 cycles during treatment.

    Measured: 12 months

  2. Event-Free Survival (EFS) at 2 Years

    Comparison of the event-free survival (EFS) between treatment CIA and FLAI, where an event is defined to be resistance to treatment, relapse (after response) or death, whichever occurred first.

    Measured: Up to 2 years or until relapse/death

  3. Overall Survival

    Time from date of treatment start until date of death due to any cause or last Follow-up.

    Measured: up to 2 years

Timeline

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

  1. First posted3 Feb 2011 (estimated)
  2. Study start2 Feb 2011
  3. Primary completion28 Jun 2017
  4. Study completion28 Jun 2017

Resources

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
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
282 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01289457
Sponsor's protocol ID
2010-0788
Other IDs
NCI-2011-00251
Status last verified
Feb 2020
First submitted
2 Feb 2011
Last updated
24 Feb 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Morita K, Kantarjian HM, Wang F, Yan Y, Bueso-Ramos C, Sasaki K, Issa GC, Wang S, Jorgensen J, Song X, Zhang J, Tippen S, Thornton R, Coyle M, Little L, Gumbs C, Pemmaraju N, Daver N, DiNardo CD, Konopleva M, Andreeff M, Ravandi F, Cortes JE, Kadia T, Jabbour E, Garcia-Manero G, Patel KP, Futreal PA, Takahashi K. Clearance of Somatic Mutations at Remission and the Risk of Relapse in Acute Myeloid Leukemia. J Clin Oncol. 2018 Jun 20;36(18):1788-1797. doi: 10.1200/JCO.2017.77.6757. Epub 2018 Apr 27.

    PubMed 29702001

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Clofarabine, Idarubicin and Cytarabine in people with Leukemia, run by M.D. Anderson Cancer Center 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 7 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: finished, as of the sponsor's last update on 24 Feb 2020. 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 24 Feb 2020). 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 (MTD) of Clofarabine, Idarubicin, and Cytarabine (time frame: 28 days). 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 NCT01289457, which also lists 1 linked publication.

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 24 Feb 2020.

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