AzTrials
AzTrials

Acute Lymphoblastic LeukemiaPhase 1/2NCT00315705

A Study of Clofarabine in Combination With Etoposide and Cyclophosphamide in Children With Acute Leukemias.

A Phase 1/2 study testing clofarabine, Etoposide and Cyclophosphamide in people with Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia, run by Genzyme, a Sanofi Company at 13 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens. This use is based on the induction of complete responses. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
clofarabine, Etoposide and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
13 sitesUnited States
Study dates
Mar 2006to May 2010
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 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • NOTE: the following eligibility criteria were applicable to acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) patients for the Phase 1 portion of this study, and to ALL patients for the Phase 2 portion of the study (only ALL patients were allowed in the Phase 2 portion of the study).
  • ALL with > 25% blasts in bone marrow; AML with ≥ 5% blasts in bone marrow; ALL and AML patients may have extramedullary disease
  • Karnofsky Performance Status ≥ 50 for patients > 10 years old; Lansky Performance Status ≥ 50 for patients ≤ 10 years old
  • Prior therapy: AML: 1-2 prior induction regimens and ≤ 1 hematopoietic stem cell transplant (HSCT); ALL: 1-3 prior induction regimens
  • Adequate liver, renal, pancreatic, and cardiac function
  • Have received no prior HSCT (study amended in Phase 2 to exclude patients with prior HSCT)

Who cannot join

  • NOTE: the following eligibility criteria were applicable to ALL and AML patients for the Phase 1 portion of this study, and to ALL patients for the Phase 2 portion of the study (only ALL patients were allowed in the Phase 2 portion of the study).
  • Burkitt's leukemia
  • Previous treatment with clofarabine
  • Uncontrolled systemic fungal, bacterial or other infection and 48 hrs negative blood cultures required for patients with a history of fever within 3 days of enrollment
  • Active CNS involvement (i.e., should be CNS1 or CNS2)
  • Inadequate time since last therapy: ≤ 14 days since last cytotoxic chemotherapy; ≤ 7 days since last biologic therapy; ≤ 14 days since last monoclonal antibody therapy
Show all 9Show fewer
  • Have received prior HSCT (study amended in Phase 2 to exclude patients with prior HSCT)
  • Pregnant or lactating
  • Have tested positive for hepatitis B or hepatitis C infection or history of cirrhosis

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites
  • Children's Hospital of Alabama

    Birmingham, Alabama

  • Dana Farber Cancer Institute

    Boston, Massachusetts

  • Children's Memorial Hospital

    Chicago, Illinois

  • Children's Hospital of Michigan

    Detroit, Michigan

  • Connecticut Children's Medical Center

    Hartford, Connecticut

  • University of Texas MD Anderson Cancer Center

    Houston, Texas

  • St. Vincent Children's Hospital

    Indianapolis, Indiana

  • Children's Hospital of Los Angeles

    Los Angeles, California

  • St. Jude Children's Research Hospital

    Memphis, Tennessee

  • Memorial Sloan-Kettering Cancer Center

    New York, New York

  • New York School of Medicine

    New York, New York

  • Rady Children's Hospital

    San Diego, California

  • Seattle Children's Hospital

    Seattle, Washington

Other trials in United States

About this study

Official title: A Phase 1/2 Dose-Escalation Study of Clofarabine in Combination With Etoposide and Cyclophosphamide in Pediatric Patients With Refractory or Relapsed Acute Leukemias.

Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens. This use is based on the induction of complete responses. Randomized trials demonstrating increased survival or other clinical benefit have not been conducted.

The purpose of the phase 1 portion of this study was to determine if clofarabine added to a combination of etoposide and cyclophosphamide is safe in children with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). The purpose of the phase 2 portion of the study was to measure the effectiveness of the combination therapy in children with ALL.

Being tested
clofarabine, Etoposide, Cyclophosphamide
Keywords
clofarabine, acute leukemia, ALL, AML, clolar, CLO218
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia

What participants receive

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

  • clofarabineDrug

    Also called Clolar, Evoltra

    Clofarabine 20-40 mg/m²/day 2 hour intravenous (IV) infusion daily for 5 days of a 28 day cycle as the first of the three IV interventions administered. Maximum of 8 cycles given in both the phase 1 and phase 2 study periods.

  • EtoposideDrug

    Also called Eposin

    Etoposide 75-100 mg/m²/day 2 hour intravenous (IV) infusion daily for 5 days of a 28 day cycle following clofarabine therapy. Maximum of 8 cycles given in both the phase 1 and phase 2 study periods.

  • CyclophosphamideDrug

    Also called Endoxan, Revimmune, Cytoxan

    Cyclophosphamide 340-440 mg/m²/day as 30-60 minute intravenous (IV) infusion daily for 5 days of a 28 day cycle following the other two interventions. Maximum of 8 cycles given in both the phase 1 and phase 2 study periods.

Study groups in NCT00315705
Study groupRoleWhat they receive
clofarabine, etoposide, cyclophosphamideExperimentalPhase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m^2, etoposide dosage from 75-100 mg/m^2, cyclophosphamide dosage from 340-440 mg/m^2. Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 delivered intravenously
Receives: Drug: clofarabine; Drug: Etoposide; Drug: Cyclophosphamide

What is being measured

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

  1. Maximum Tolerated Dose (MTD) in Phase 1

    The MTD was to be the highest dose level of clofarabine in combination with etoposide and cyclophosphamide that caused <= 1 of 6 participants to experience a dose limiting toxicity (DLT) with the next higher dose level having at least 2 of 3 or 2 of 6 participants experiencing a DLT. The MTD would be used as the recommended phase 2 dose (RP2D). If the MTD could not be determined, then the target dose of clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 as taken by Cohort 5 was to become the RP2D.

    The rating scale used is 0 = not the MTD, 1 = the MTD.

    Measured: Up to Day 42 (Phase 1 portion of study)

  2. Participants With Dose Limiting Toxicity in Phase 1

    The number of participants in each cohort that had dose limiting toxicity is summarized. Toxicities were reviewed by an independent Data Safety Monitoring Board (DSMB) who determined if additional participants should be added to the cohort and the criteria for escalating to the next cohort.

    Measured: Up to Day 42 (Phase 1 portion of study)

  3. Percentage of Participants Achieving A Response Over the First Two Treatment Cycles in Phase 2

    Response categories 1) complete remission (CR): without circulating blasts or extramedullary disease, bone marrow (BM) with <5% blasts, and platelet (plt)/ANC recovery: ≥75/ ≥0.75 [x 10^9/L] 2) CR in absence of plt recovery (CRp): plt ≥20 to <75 x 10^9/L 3) partial remission (PR): no circulating blasts, appearance of normal hematopoietic progenitors, and either a BM with ≥5% and ≤25% blasts with recovery of plts/ANC or a BM with <5% blasts not meeting CR/CRp definition 4) Overall remission (OR): CR+CRp 5) Any response: CR+CRp+PR.

    Measured: Approximately 28-56 days (Phase 2 portion of study)

Secondary outcomes (13)
  1. Summary of Participants With Adverse Events (AEs) in Phase 1

    Number of participants with AEs that occurred during treatment and follow-up period (45 days after last cycle). Drug-related AEs and SAEs were followed until resolved or mutually agreed by the investigator and Genzyme to discontinue reporting. AEs were classified by the investigator according to severity (graded using National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 3.0) and relationship to study drug. The severity scale is:> Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death related to AE

    Measured: Up to 9.5 months (Phase 1 portion of study)

  2. Percentage of Participants Achieving A Response Over the First Two Treatment Cycles in Phase 1

    Response categories 1) complete remission (CR): without circulating blasts or extramedullary disease, bone marrow (BM) with <5% blasts, and platelet (plt)/ANC recovery: ALL ≥75/ ≥0.75 [x 10^9/L]; AML ≥100/ ≥1.0 [x 10^9/L] 2) CR in absence of plt recovery (CRp): ALL plt ≥20 to <75 x 10^9/L; AML plt ≥20 to <100 x 10^9/L 3) partial remission (PR): no circulating blasts, appearance of normal hematopoietic progenitors, and either a BM with ≥5% and ≤25% blasts with recovery of plts/ANC or a BM with <5% blasts not meeting CR/CRp definition 4) Overall remission (OR): CR+CRp 5) Any response: CR+CRp+PR.

    Measured: Approximately 2 months (Phase 1 portion of study)

  3. Time to Remission for Participants Who Had a Response in Phase 1

    The weeks between start of intervention and remission as assessed by the investigator in Phase 1. Participants who had a complete remission (CR) or complete remission with the absence of total platelet recovery (CRp) are included.

    Measured: up to 8 weeks (Phase 1 portion of study)

  4. Kaplan Meier Estimate of Duration of Remission (DOR) for Participants Who Achieved Overall Remission (OR) in Phase 1

    Duration of response is the time from the first objective measurement of complete response (CR) or complete response with the absence of total platelet recovery (CRp) to the date of first objective documentation of disease relapse or death due to any cause, plus one day. For summary purposes, results are presented as weeks.

    Measured: Up to 2 years (Phase 1 portion of study)

  5. Kaplan Meier Estimates of Event-free Survival (EFS) for Participants in Phase 1

    Event-free survival (EFS) is defined as the time from date of first administration of study interventions until the earliest of the following: date of death or date of first response assessment confirming relapse or date of final response assessment which fails to confirm response, plus one day. For summary purposes, results are presented as weeks.

    Measured: Up to 2 years (Phase 1 portion of study)

  6. Number of Participants With 4-month Event Free Survival in Phase 1

    Number of participants with event-free survival at four months post first dose of therapy. A participant is considered event-free if at month 4 they have not died or had a response assessment confirming a relapse.

    Measured: 4 months (Phase I portion of study)

  7. Kaplan Meier Estimates of Overall Survival (OS) for Participants in Phase 1

    Overall survival is defined as the time from date of first administration of study interventions until date of death, plus one day. For summary purposes, results are presented as weeks.

    Measured: Up to 2 years (Phase 1 portion of study)

  8. Summary of Participants With Adverse Events (AEs) in Phase 2

    Number of participants with AEs that occurred during treatment and follow-up period (45 days after last cycle). Drug-related AEs and SAEs were followed until resolved or mutually agreed by the investigator and Genzyme to discontinue reporting. AEs were classified by the investigator according to severity (graded using National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 3.0) and relationship to study drug. The severity scale is:> Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death related to AE

    Measured: Up to 9.5 months (Phase 2 portion of study)

  9. Time to Remission for Participants Who Had a Response in Phase 2

    The weeks between start of intervention and remission as assessed by the investigator in Phase 2. Participants who had a complete remission (CR) or complete remission with the absence of total platelet recovery (CRp) are included.

    Measured: up to 8 weeks (Phase 2 portion of study)

  10. Kaplan Meier Estimate of Duration of Remission (DOR) for Participants Who Achieved Overall Remission (OR) in Phase 2

    Duration of response is the time from the first objective measurement of complete response (CR) or complete response with the absence of total platelet recovery (CRp) to the date of first objective documentation of disease relapse or death due to any cause, plus one day. For summary purposes, results are presented as weeks.

    Measured: Up to 2 years (Phase 2 portion of study)

  11. Kaplan Meier Estimates of Event-free Survival (EFS) for Participants in Phase 2

    Event-free survival (EFS) is defined as the time from date of first administration of study interventions until the earliest of the following: date of death or date of first response assessment confirming relapse or date of final response assessment which fails to confirm response, plus one day. For summary purposes, results are presented as weeks.

    Measured: Up to 2 years (Phase 2 portion of study)

  12. Number of Participants With 4-month Event Free Survival in Phase 2

    Number of participants with event-free survival at four months post first dose of therapy. A participant is considered event-free if at month 4 they have not died or had a response assessment confirming a relapse.

    Measured: 4 months (Phase 2 portion of study)

  13. Kaplan Meier Estimates of Overall Survival (OS) for Participants in Phase 2

    Overall survival is defined as the time from date of first administration of study interventions until date of death, plus one day. For summary purposes, results are presented as weeks.

    Measured: Up to 2 years (Phase 2 portion of study)

Timeline

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

  1. First posted19 Apr 2006 (estimated)
  2. Study startMar 2006
  3. Primary completionMay 2010
  4. Study completionMay 2010

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00315705
Sponsor's protocol ID
CLO21800205
Status last verified
Mar 2014
First submitted
18 Apr 2006
Last updated
14 Apr 2014
Data monitoring committee
No

Publications

  • Hijiya N, Thomson B, Isakoff MS, Silverman LB, Steinherz PG, Borowitz MJ, Kadota R, Cooper T, Shen V, Dahl G, Thottassery JV, Jeha S, Maloney K, Paul JA, Barry E, Carroll WL, Gaynon PS. Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. Blood. 2011 Dec 1;118(23):6043-9. doi: 10.1182/blood-2011-08-374710. Epub 2011 Oct 3.

    PubMed 21967976

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing clofarabine, Etoposide and Cyclophosphamide in people with Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia, run by Genzyme, a Sanofi Company at 13 sites 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 6 inclusion and 9 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 14 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites 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 30 Jun 2011). 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) in Phase 1 (time frame: Up to Day 42 (Phase 1 portion of study)). The study lists 3 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 NCT00315705, 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 14 Apr 2014.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in