L1 Childhood Acute Lymphoblastic LeukemiaNCT00049569
Combination Chemotherapy and Imatinib Mesylate in Treating Children With Relapsed Acute Lymphoblastic Leukemia
A study testing cytarabine, methotrexate and vincristine sulfate in people with L1 Childhood Acute Lymphoblastic Leukemia and L2 Childhood Acute Lymphoblastic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Combining more than one chemotherapy drug with imatinib mesylate may kill more cancer cells. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- L1 Childhood Acute Lymphoblastic Leukemia, L2 Childhood Acute Lymphoblastic Leukemia, Non-T, Non-B Childhood Acute Lymphoblastic Leukemia
- What is being tested?
- cytarabine, methotrexate and vincristine sulfate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2003to Mar 2006
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Patients with acute lymphoblastic leukemia (ALL) in first relapse involving the bone marrow (M3 marrow), with or without associated extramedullary disease; this includes patients who are Philadelphia chromosome-positive
- Shortening fraction of >= 28% by echocardiogram, or ejection fraction of >= 50% by gated radionuclide study
- Cumulative prior anthracycline exposure of =< 350 mg/m^2 (each 10 mg/m^2 dose of idarubicin should be calculated as the isotoxic equivalent of 50 mg/m^2 of daunorubicin or adriamycin)
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Who cannot join
- Patients with B-cell ALL (L3 morphology or evidence of myc translocation by molecular or cytogenetic technique) are not eligible
- Patients with Down syndrome are excluded due to the administration of methotrexate in Block 2
- Patients who have undergone prior stem cell transplantation (SCT) are ineligible if:
- They received SCT less than 12 months prior to study entry
- They are still receiving immunosuppression for the treatment of graft-versus-host disease (GVHD)
- They have active fungal infection at time of study entry
Show all 9Show fewer
- They have had invasive filamentous fungal infection at any time post-SCT
- Pregnant or lactating females are ineligible as the medications used in this protocol could be harmful to unborn children and infants
- Patients with prior isolated extramedullary relapse are ineligible
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Oncology Group
Arcadia, California, 91006-3776
About this study
Official title: Intensive Induction Therapy for Children With Acute Lymphoblastic Leukemia (ALL) Who Experience a Bone Marrow Relapse
Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Combining more than one chemotherapy drug with imatinib mesylate may kill more cancer cells. Randomized phase II trial to study the effectiveness of combination chemotherapy and imatinib mesylate in treating children who have relapsed acute lymphoblastic leukemia.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the feasibility and safety of using an intensified sequential induction regimen to treat children with acute lymphoblastic leukemia (ALL), who experience an isolated, or combined bone marrow relapse.
II. To determine the potential of this regimen to serve, as a backbone, for the future testing of novel therapeutic agents.
SECONDARY OBJECTIVES:
- To estimate the remission re-induction rates and four-month event-free survival (EFS) for children, stratified by the duration of first remission.
II. To determine the feasibility of measuring minimal residual disease (MRD) quantitatively in all patients at time points throughout re-induction, and to correlate post-remission events with disease burden during induction.
III. To use deoxyribonucleic acid (DNA) arrays to characterize patterns of gene expression that predict treatment failure, and to compare gene expression profiles at the time of relapse with those at the time of initial diagnosis to gain an understanding of the pathways that may be involved in disease recurrence.
IV. To determine the feasibility of combining intensive re-induction therapy with imatinib mesylate (STI571) for children with a relapse of Philadelphia chromosome positive (Ph+) ALL.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I:
Treatment Block 1: Patients receive cytarabine intrathecally (IT) on day 1 and methotrexate IT on days 15 and 29. Patients also receive vincristine intravenously (IV) on days 1, 8, 15, and 22; prednisone orally (PO) twice or thrice daily (BID or TID) on days 1-29; pegaspargase intramuscularly (IM) on days 2, 8, 15, and 22; and doxorubicin IV over 15 minutes on day 1. Ph-positive patients also receive imatinib mesylate PO on days 1-14.
Treatment Block 2: Patients receive methotrexate IT on days 1 and 22, cyclophosphamide IV over 30 minutes and etoposide IV over 2 hours on days 1-5, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 6 and continuing until blood counts recover. Patients also receive methotrexate IV over 24 hours on day 22 followed by leucovorin calcium IV every 6 hours on days 24 and 25. Ph-positive patients receive imatinib mesylate PO on days 1-14.
Treatment Block 3a (Ph-negative patients): Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9, asparaginase IM on days 2 and 9, and G-CSF SC beginning on day 10 and continuing until blood counts recover.
Treatment Block 3b (Ph-positive patients): Patients receive cytarabine IV over 3 hours every 12 hours on days 1 and 2, asparaginase IM on day 2, and G-CSF SC beginning on day 3 and continuing until blood counts recover. Patients also receive imatinib mesylate PO on days 1-14.
ARM II:
Treatment Block 1: Patients receive cytarabine IT on day 1 and then methotrexate, cytarabine and hydrocortisone IT (triple intrathecal therapy; TIT) on days 8, 15, 22, and 29. Vincristine, prednisone, pegaspargase, doxorubicin, and imatinib mesylate are administered as in arm I.
Treatment Block 3: Patients receive cytarabine, asparaginase, G-CSF, and imatinib mesylate as in arm I.
Treatment Block 2: Patients receive TIT on days 1 and 22. Patients then receive cyclophosphamide, etoposide, G-CSF, methotrexate IV, leucovorin calcium, and imatinib mesylate as in arm I. After each block is completed, disease is assessed. The next block is started on day 36 if blood counts have recovered and marrow during block 1 is at least M2/M3. Patients are removed from protocol therapy if disease progresses, unacceptable toxicity occurs, marrow is M2/M3 at day 15 of the second administered block of treatment, or cerebrospinal fluid blasts persist after 6 weekly doses of TIT.
After completion of study treatment, patients are followed up for 4 months.
PROJECTED ACCRUAL: A total of 63-126 patients will be accrued for this study within 14 months.
- Conditions
- L1 Childhood Acute Lymphoblastic Leukemia, L2 Childhood Acute Lymphoblastic Leukemia, Non-T, Non-B Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Lymphoblastic Leukemia, T-cell Childhood Acute Lymphoblastic Leukemia
- Being tested
- cytarabine, methotrexate, vincristine sulfate, prednisone, pegaspargase
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cytarabineDrug
Given IT
methotrexateDrug
Given IT
Given IV
prednisoneDrug
Given PO
pegaspargaseDrug
Given IM
Given IV
imatinib mesylateDrug
Given PO
cyclophosphamideDrug
Given IV
etoposideDrug
Given IV
filgrastimBiological
Given SC
Given IV
asparaginaseDrug
Given IM
therapeutic hydrocortisoneDrug
Given IT
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | See detailed description. Receives: Drug: cytarabine; Drug: methotrexate; Drug: vincristine sulfate; Drug: prednisone; Drug: pegaspargase; Drug: doxorubicin hydrochloride; Drug: imatinib mesylate; Drug: cyclophosphamide; Drug: etoposide; Biological: filgrastim; Drug: leucovorin calcium; Drug: asparaginase |
| Arm II | Experimental | See detailed description. Receives: Drug: cytarabine; Drug: methotrexate; Drug: vincristine sulfate; Drug: prednisone; Drug: pegaspargase; Drug: doxorubicin hydrochloride; Drug: imatinib mesylate; Drug: cyclophosphamide; Drug: etoposide; Biological: filgrastim; Drug: leucovorin calcium; Drug: asparaginase; Drug: therapeutic hydrocortisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility assessed by excessive early deaths, induction failures, and early relapses
Measured: Up to 4 months
Toxicity assessed using CTC version 2.0
Will be tabulated in detail.
Measured: Up to 4 months
Secondary outcomes (5)
Overall remission reinduction (CR2) rate
Measured: Up to 4 months
EFS
The Kaplan-Meier method will be used.
Measured: 4 months
MRD
The percentage of MRD positive patients will be estimated at the end of each block. Cox regression will be utilized to correlate MRD values with EFS.
Measured: Up to 4 months
Feasibility of combining intensive re-induction therapy with imatinib mesylate
Will be determined using descriptive statistics due to the small sample size.
Measured: Up to 4 months
Percentage of patients who were able to complete the triple re-induction therapy with imatinib mesylate
Will be estimated.
Measured: Up to 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startJan 2003
- Primary completionMar 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for L1 Childhood Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 126 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Elizabeth Raetz, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00049569
- Sponsor's protocol ID
- NCI-2012-01798
- Other IDs
- NCI-2012-01798, COG-AALL01P2, CDR0000258120, AALL01P2, AALL01P2, U10CA098543
- Status last verified
- Oct 2013
- First submitted
- 12 Nov 2002
- Last updated
- 8 Oct 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intensive Induction Therapy for Children With Acute Lymphoblastic Leukemia (ALL) Who Experience a Bone Marrow Relapse
- ClinicalTrials.gov ID
- NCT00049569
- Acronym / sponsor ID
- NCI-2012-01798
- Conditions
- L1 Childhood Acute Lymphoblastic Leukemia, L2 Childhood Acute Lymphoblastic Leukemia, Non-T, Non-B Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Lymphoblastic Leukemia, T-cell Childhood Acute Lymphoblastic Leukemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 126 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 2003
- Primary completion
- Mar 2006 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Combining more than one chemotherapy drug with imatinib mesylate may kill more cancer cells. Randomized phase II trial to study the effectiveness of combination chemotherapy and imatinib mesylate in treating children who have relapsed acute lymphoblastic leukemia.
Detailed description
PRIMARY OBJECTIVES:
- To assess the feasibility and safety of using an intensified sequential induction regimen to treat children with acute lymphoblastic leukemia (ALL), who experience an isolated, or combined bone marrow relapse.
II. To determine the potential of this regimen to serve, as a backbone, for the future testing of novel therapeutic agents.
SECONDARY OBJECTIVES:
- To estimate the remission re-induction rates and four-month event-free survival (EFS) for children, stratified by the duration of first remission.
II. To determine the feasibility of measuring minimal residual disease (MRD) quantitatively in all patients at time points throughout re-induction, and to correlate post-remission events with disease burden during induction.
III. To use deoxyribonucleic acid (DNA) arrays to characterize patterns of gene expression that predict treatment failure, and to compare gene expression profiles at the time of relapse with those at the time of initial diagnosis to gain an understanding of the pathways that may be involved in disease recurrence.
IV. To determine the feasibility of combining intensive re-induction therapy with imatinib mesylate (STI571) for children with a relapse of Philadelphia chromosome positive (Ph+) ALL.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I:
Treatment Block 1: Patients receive cytarabine intrathecally (IT) on day 1 and methotrexate IT on days 15 and 29. Patients also receive vincristine intravenously (IV) on days 1, 8, 15, and 22; prednisone orally (PO) twice or thrice daily (BID or TID) on days 1-29; pegaspargase intramuscularly (IM) on days 2, 8, 15, and 22; and doxorubicin IV over 15 minutes on day 1. Ph-positive patients also receive imatinib mesylate PO on days 1-14.
Treatment Block 2: Patients receive methotrexate IT on days 1 and 22, cyclophosphamide IV over 30 minutes and etoposide IV over 2 hours on days 1-5, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 6 and continuing until blood counts recover. Patients also receive methotrexate IV over 24 hours on day 22 followed by leucovorin calcium IV every 6 hours on days 24 and 25. Ph-positive patients receive imatinib mesylate PO on days 1-14.
Treatment Block 3a (Ph-negative patients): Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9, asparaginase IM on days 2 and 9, and G-CSF SC beginning on day 10 and continuing until blood counts recover.
Treatment Block 3b (Ph-positive patients): Patients receive cytarabine IV over 3 hours every 12 hours on days 1 and 2, asparaginase IM on day 2, and G-CSF SC beginning on day 3 and continuing until blood counts recover. Patients also receive imatinib mesylate PO on days 1-14.
ARM II:
Treatment Block 1: Patients receive cytarabine IT on day 1 and then methotrexate, cytarabine and hydrocortisone IT (triple intrathecal therapy; TIT) on days 8, 15, 22, and 29. Vincristine, prednisone, pegaspargase, doxorubicin, and imatinib mesylate are administered as in arm I.
Treatment Block 3: Patients receive cytarabine, asparaginase, G-CSF, and imatinib mesylate as in arm I.
Treatment Block 2: Patients receive TIT on days 1 and 22. Patients then receive cyclophosphamide, etoposide, G-CSF, methotrexate IV, leucovorin calcium, and imatinib mesylate as in arm I. After each block is completed, disease is assessed. The next block is started on day 36 if blood counts have recovered and marrow during block 1 is at least M2/M3. Patients are removed from protocol therapy if disease progresses, unacceptable toxicity occurs, marrow is M2/M3 at day 15 of the second administered block of treatment, or cerebrospinal fluid blasts persist after 6 weekly doses of TIT.
After completion of study treatment, patients are followed up for 4 months.
PROJECTED ACCRUAL: A total of 63-126 patients will be accrued for this study within 14 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: cytarabine, Drug: methotrexate, Drug: vincristine sulfate, Drug: prednisone, Drug: pegaspargase, Drug: doxorubicin hydrochloride, Drug: imatinib mesylate, Drug: cyclophosphamide, Drug: etoposide, Biological: filgrastim, Drug: leucovorin calcium, Drug: asparaginaseSee detailed description. |
| Arm II | Experimental | Drug: cytarabine, Drug: methotrexate, Drug: vincristine sulfate, Drug: prednisone, Drug: pegaspargase, Drug: doxorubicin hydrochloride, Drug: imatinib mesylate, Drug: cyclophosphamide, Drug: etoposide, Biological: filgrastim, Drug: leucovorin calcium, Drug: asparaginase, Drug: therapeutic hydrocortisoneSee detailed description. |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Patients with acute lymphoblastic leukemia (ALL) in first relapse involving the bone marrow (M3 marrow), with or without associated extramedullary disease; this includes patients who are Philadelphia chromosome-positive
- Shortening fraction of >= 28% by echocardiogram, or ejection fraction of >= 50% by gated radionuclide study
- Cumulative prior anthracycline exposure of =< 350 mg/m^2 (each 10 mg/m^2 dose of idarubicin should be calculated as the isotoxic equivalent of 50 mg/m^2 of daunorubicin or adriamycin)
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Key exclusion criteria (9 listed)
- Patients with B-cell ALL (L3 morphology or evidence of myc translocation by molecular or cytogenetic technique) are not eligible
- Patients with Down syndrome are excluded due to the administration of methotrexate in Block 2
- Patients who have undergone prior stem cell transplantation (SCT) are ineligible if:
- Pregnant or lactating females are ineligible as the medications used in this protocol could be harmful to unborn children and infants
- Patients with prior isolated extramedullary relapse are ineligible
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 |
|---|---|---|
| cytarabineGiven IT | Drug | Arm I, Arm II |
| methotrexateGiven IT | Drug | Arm I, Arm II |
| vincristine sulfateGiven IV | Drug | Arm I, Arm II |
| prednisoneGiven PO | Drug | Arm I, Arm II |
| pegaspargaseGiven IM | Drug | Arm I, Arm II |
| doxorubicin hydrochlorideGiven IV | Drug | Arm I, Arm II |
| imatinib mesylateGiven PO | Drug | Arm I, Arm II |
| cyclophosphamideGiven IV | Drug | Arm I, Arm II |
| etoposideGiven IV | Drug | Arm I, Arm II |
| filgrastimGiven SC | Biological | Arm I, Arm II |
| leucovorin calciumGiven IV | Drug | Arm I, Arm II |
| asparaginaseGiven IM | Drug | Arm I, Arm II |
| therapeutic hydrocortisoneGiven IT | Drug | Arm II |
Primary outcome
Feasibility assessed by excessive early deaths, induction failures, and early relapses
Time frame: Up to 4 months
Toxicity assessed using CTC version 2.0
Time frame: Up to 4 months
Will be tabulated in detail.
5 secondary outcomes
Overall remission reinduction (CR2) rate
Time frame: Up to 4 months
EFS
Time frame: 4 months
MRD
Time frame: Up to 4 months
Feasibility of combining intensive re-induction therapy with imatinib mesylate
Time frame: Up to 4 months
Percentage of patients who were able to complete the triple re-induction therapy with imatinib mesylate
Time frame: Up to 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2013.
Related trials for L1 Childhood Acute Lymphoblastic Leukemia
Active, not recruitingPhase 2
Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia, Adult B Acute Lymphoblastic Leukemia
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.
Elizabeth Raetz principal investigator
Children's Oncology Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing cytarabine, methotrexate and vincristine sulfate in people with L1 Childhood Acute Lymphoblastic Leukemia and L2 Childhood Acute Lymphoblastic Leukemia, run by National Cancer Institute (NCI) 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 5 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 8 Oct 2013. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Feasibility assessed by excessive early deaths, induction failures, and early relapses (time frame: Up to 4 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?
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 8 Oct 2013.