LeukemiaNCT01225874
Biomarkers to Classify Young Patients With Acute Lymphoblastic Leukemia (ALL) and Remission Induction Therapy in Young Patients With B-Precursor ALL
A study testing SC-PEG E. coli L-asparaginase, cytarabine and daunorubicin hydrochloride in people with Leukemia, run by Children's Oncology Group.
Trial summary
RATIONALE: Studying samples of blood or bone marrow from patients with cancer in the laboratory may help doctors predict how well patients will respond to treatment. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Leukemia
- What is being tested?
- SC-PEG E. coli L-asparaginase, cytarabine and daunorubicin hydrochloride
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,762 participants
- Where
- No sites listed yet
- Study dates
- Dec 1999to 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Meets one of the following sets of criteria:
- Classification study:
- Newly diagnosed ALL*
- Must have one of the following:
- ≥ 25% blasts in bone marrow
- ≥ 100,000/μl peripheral blood WBC with ≥ 75% blasts, if bone marrow aspiration is omitted for any reason other than medical contraindication
- ≥ 30,000/μl WBC with ≥ 75% blasts, if bone marrow aspiration is omitted because of medical contraindication
- Immunophenotype and Wright's stain morphology of blast cells consistent with acute lymphocytic leukemia
- ≤ 21 years of age at the time of diagnosis
- No previous registration on 9900
- Samples must be sent for local institution and COG Reference Laboratory studies NOTE: *It is urged that a bone marrow aspiration be performed for every patient with suspected ALL. However, a marrow is not required for patients with ≥ 100,000/μl peripheral blood WBC and ≥ 75% blasts or for those patients whose clinical condition precludes performing the procedure safely. Patients with a medical contraindication to the procedure must be discussed with one of the study coordinators and must have a peripheral blood WBC of ≥ 30,000/μl with ≥ 75% blasts.
- Induction therapy study:
- Patients must have a confirmed diagnosis of B-precursor acute lymphoblastic leukemia
- Patients must be 1.001 to 21.999 years at diagnosis NOTE: Patients meeting all of the above eligibility criteria are eligible for registration on 9900 whether or not they are to be entered on a COG frontline protocol for treatment of newly diagnosed ALL. Registration on 9900 is required for all legacy POG institution patients in order to be eligible for entry on the following COG ALL studies, which are either currently open or only temporarily closed: P9407, 9904, 9905, 9907, AALL0031 and AALL00P2.
PATIENT CHARACTERISTICS:
- See Disease Characteristics
PRIOR CONCURRENT THERAPY:
- Previously untreated, with the following exception:
- Steroid treatment* in the 48-hour period just prior to study entry will be allowed provided that a physical examination and CBC with differential were performed IMMEDIATELY prior to beginning steroids and results of both are known NOTE: *Patients on chronic steroid treatment for another disease are NOT eligible for a COG New ALL protocol.
About this study
Official title: ALinC 17, Classification ©), B-precursor Induction Treatment (I)
RATIONALE: Studying samples of blood or bone marrow from patients with cancer in the laboratory may help doctors predict how well patients will respond to treatment. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This trial is studying biomarkers to classify young patients with acute lymphoblastic leukemia (ALL) and remission induction therapy in young patients with B-precursor ALL.
Read the detailed description
OBJECTIVES:
- To provide the clinical and laboratory data necessary for placing each patient with ALL onto the proper therapeutic trial. (Classification)
- To provide an administrative base to capture classification data for correlative studies in ALL treatment protocols and series of historical protocols. (Classification)
- To provide appropriate induction regimens for patients who may then enter risk specific, post-induction therapeutic trials. (Induction therapy)
- To determine the correlation between event-free survival (EFS) and the following measures of minimal-residual disease (MRD)/early response (ER): 1) the rate of peripheral blast count disappearance and the absolute blast count on day 8 as determined morphologically, by flow cytometry, and using molecular techniques; 2) Marrow morphology on day 8, and; 3) MRD as determined by flow cytometry and molecular techniques on bone marrow and peripheral blood samples on day 29. (Induction therapy)
OUTLINE: This is a multicenter study.
- Classification study: Bone marrow or peripheral blood samples are collected and may be analyzed for B- and T-lineage antigen screening; cytochemical stains; cytogenetics (karyotype); immunophenotype screening for MLL, E2A-PBX1, TEL-AML1; immunophenotype detection of minimal-residual disease (MRD); FCM ploidy (DNA index); trisomies 4 and 10 (FISH); molecular testing for BCR/ABL, MLL rearrangements, E2A-PBX1, and TEL-AML1; molecular detection of MRD - Tγ, Tδ, or IgH; acute lymphoblastic leukemia (ALL) cell bank; special T-ALL reference laboratory studies (role of tumor suppressor genes in T-ALL and drug sensitivity profiles in T-ALL); special study for mature B-ALL [t(18;14)(a24;q32)] by FISH; and hematopathology consultation concerning morphology and cytochemistry. The immunophenotype results are used to assign patients to a treatment protocol, to assign patients to post-induction (day 28) risk group and treatment for patients with B-precursor (non-T, non-B) ALL, and to use as reference laboratory MRD results.
- Induction therapy study: Patients are entered on stratum 3 (three drugs) for NCI consensus standard-risk disease (age < 10 years and WBC < 50,000/mm³) or stratum 4 (four drugs) induction therapy for NCI consensus high-risk disease (age ≥ 10 years and/or WBC ≥ 50,000/mm³ or CNS3 disease or testicular disease).
- Stratum 3: Patients receive oral dexamethasone twice daily on days 1-28; vincristine sulfate IV on days 1, 8, 15, and 22; pegaspargase intramuscularly (IM) on day 4, 5, or 6; cytarabine intrathecally (IT) on day 1; and methotrexate IT on day 8 (some patients also receive methotrexate IT on days 15 and 22).
- Stratum 4: Patients receive oral prednisone twice daily on days 1-28; vincristine sulfate IV on days 1, 8, 15, and 22; IM SC-PEG E. coli asparaginase IM on days 2, 5, 8, 12, 15, and 19; daunorubicin hydrochloride IV over 15-20 minutes on days 8, 15, and 22; and methotrexate IT on days 1 and 8 (some patients also receive methotrexate IT on days 15 and 22).
Based on day 29 bone marrow results, patients may start consolidation therapy, undergo retesting in a week, or receive 2 additional weeks of therapy. Additional therapy comprises oral prednisone thrice daily for 14 days; vincristine sulfate IV and daunorubicin hydrochloride IV over 15-20 minutes on days 29 and 36; and IM pegaspargase on day 29, 30, or 31. After successful remission induction, patients are assigned to COG-P9904, COG-P9905, or COG-P9906 based on the classification study.
Patients undergo bone marrow aspiration on day 8 to determine the prognostic significance of early remission in the context of this therapy.
After completion of study treatment, patients are followed up every 6 months for 4 years and annually thereafter.
- Conditions
- Leukemia
- Being tested
- SC-PEG E. coli L-asparaginase, cytarabine, daunorubicin hydrochloride, dexamethasone, methotrexate
- Keywords
- untreated childhood acute lymphoblastic leukemia, B-cell childhood acute lymphoblastic leukemia, non-T, non-B, cALLa positive, pre-B childhood acute lymphoblastic leukemia
- Medical subject headings
- Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SC-PEG E. coli L-asparaginaseDrug
Given IM
cytarabineDrug
Given IT
daunorubicin hydrochlorideDrug
Given IV
dexamethasoneDrug
Given orally
methotrexateDrug
Given IT
pegaspargaseDrug
Given IM
prednisoneDrug
Given orally
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Stratum 3 | Experimental | Patients receive oral dexamethasone twice daily on days 1-28; vincristine sulfate IV on days 1, 8, 15, and 22; pegaspargase intramuscularly (IM) on day 4, 5, or 6; cytarabine intrathecally (IT) on day 1; and methotrexate IT on day 8 (some patients also receive methotrexate IT on days 15 and 22). Receives: Drug: cytarabine; Drug: dexamethasone; Drug: methotrexate; Drug: pegaspargase; Drug: vincristine sulfate |
| Stratum 4 | Experimental | Patients receive oral prednisone twice daily on days 1-28; vincristine sulfate IV on days 1, 8, 15, and 22; IM SC-PEG E. coli asparaginase on days 2, 5, 8, 12, 15, and 19; daunorubicin hydrochloride IV over 15-20 minutes on days 8, 15, and 22; and methotrexate IT on days 1 and 8 (some patients also receive methotrexate IT on days 15 and 22). Receives: Drug: SC-PEG E. coli L-asparaginase; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: methotrexate; Drug: prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Collection of the clinical and laboratory data necessary for placing patients with acute lymphoblastic leukemia (ALL) onto the proper therapeutic trial (Classification)
Creation of an administrative base to capture classification data for correlative studies in ALL treatment protocols and series of historical protocols (Classification)
Creation of appropriate induction regimens for patients (Induction therapy)
Correlation between event-free survival and measures of minimal-residual disease/early response
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2010 (estimated)
- Study startDec 1999
- Primary completionMar 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3,762 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Dale J. Pullen, MD, Study chair, University of Mississippi Cancer Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01225874
- Sponsor's protocol ID
- 9900
- Other IDs
- U10CA030969, COG-9900, POG-9900, CDR0000078618
- Status last verified
- Feb 2016
- First submitted
- 20 Oct 2010
- Last updated
- 23 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Escherich CS, Chen W, Li Y, Yang W, Nishii R, Li Z, Raetz EA, Devidas M, Wu G, Nichols KE, Inaba H, Pui CH, Jeha S, Camitta BM, Larsen E, Hunger SP, Loh ML, Yang JJ. Germ line genetic NBN variation and predisposition to B-cell acute lymphoblastic leukemia in children. Blood. 2024 May 30;143(22):2270-2283. doi: 10.1182/blood.2023023336.
PubMed 38446568
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ALinC 17, Classification ©), B-precursor Induction Treatment (I)
- ClinicalTrials.gov ID
- NCT01225874
- Acronym / sponsor ID
- 9900
- Conditions
- Leukemia
- Keywords
- untreated childhood acute lymphoblastic leukemia, B-cell childhood acute lymphoblastic leukemia, non-T, non-B, cALLa positive, pre-B childhood acute lymphoblastic leukemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,762 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 1999
- Primary completion
- Mar 2006 (actual)
- First posted
- 21 Oct 2010 (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.
RATIONALE: Studying samples of blood or bone marrow from patients with cancer in the laboratory may help doctors predict how well patients will respond to treatment. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This trial is studying biomarkers to classify young patients with acute lymphoblastic leukemia (ALL) and remission induction therapy in young patients with B-precursor ALL.
Detailed description
OBJECTIVES:
- To provide the clinical and laboratory data necessary for placing each patient with ALL onto the proper therapeutic trial. (Classification)
- To provide an administrative base to capture classification data for correlative studies in ALL treatment protocols and series of historical protocols. (Classification)
- To provide appropriate induction regimens for patients who may then enter risk specific, post-induction therapeutic trials. (Induction therapy)
- To determine the correlation between event-free survival (EFS) and the following measures of minimal-residual disease (MRD)/early response (ER): 1) the rate of peripheral blast count disappearance and the absolute blast count on day 8 as determined morphologically, by flow cytometry, and using molecular techniques; 2) Marrow morphology on day 8, and; 3) MRD as determined by flow cytometry and molecular techniques on bone marrow and peripheral blood samples on day 29. (Induction therapy)
OUTLINE: This is a multicenter study.
- Classification study: Bone marrow or peripheral blood samples are collected and may be analyzed for B- and T-lineage antigen screening; cytochemical stains; cytogenetics (karyotype); immunophenotype screening for MLL, E2A-PBX1, TEL-AML1; immunophenotype detection of minimal-residual disease (MRD); FCM ploidy (DNA index); trisomies 4 and 10 (FISH); molecular testing for BCR/ABL, MLL rearrangements, E2A-PBX1, and TEL-AML1; molecular detection of MRD - Tγ, Tδ, or IgH; acute lymphoblastic leukemia (ALL) cell bank; special T-ALL reference laboratory studies (role of tumor suppressor genes in T-ALL and drug sensitivity profiles in T-ALL); special study for mature B-ALL [t(18;14)(a24;q32)] by FISH; and hematopathology consultation concerning morphology and cytochemistry. The immunophenotype results are used to assign patients to a treatment protocol, to assign patients to post-induction (day 28) risk group and treatment for patients with B-precursor (non-T, non-B) ALL, and to use as reference laboratory MRD results.
- Induction therapy study: Patients are entered on stratum 3 (three drugs) for NCI consensus standard-risk disease (age < 10 years and WBC < 50,000/mm³) or stratum 4 (four drugs) induction therapy for NCI consensus high-risk disease (age ≥ 10 years and/or WBC ≥ 50,000/mm³ or CNS3 disease or testicular disease).
- Stratum 3: Patients receive oral dexamethasone twice daily on days 1-28; vincristine sulfate IV on days 1, 8, 15, and 22; pegaspargase intramuscularly (IM) on day 4, 5, or 6; cytarabine intrathecally (IT) on day 1; and methotrexate IT on day 8 (some patients also receive methotrexate IT on days 15 and 22).
- Stratum 4: Patients receive oral prednisone twice daily on days 1-28; vincristine sulfate IV on days 1, 8, 15, and 22; IM SC-PEG E. coli asparaginase IM on days 2, 5, 8, 12, 15, and 19; daunorubicin hydrochloride IV over 15-20 minutes on days 8, 15, and 22; and methotrexate IT on days 1 and 8 (some patients also receive methotrexate IT on days 15 and 22).
Based on day 29 bone marrow results, patients may start consolidation therapy, undergo retesting in a week, or receive 2 additional weeks of therapy. Additional therapy comprises oral prednisone thrice daily for 14 days; vincristine sulfate IV and daunorubicin hydrochloride IV over 15-20 minutes on days 29 and 36; and IM pegaspargase on day 29, 30, or 31. After successful remission induction, patients are assigned to COG-P9904, COG-P9905, or COG-P9906 based on the classification study.
Patients undergo bone marrow aspiration on day 8 to determine the prognostic significance of early remission in the context of this therapy.
After completion of study treatment, patients are followed up every 6 months for 4 years and annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stratum 3 | Experimental | Drug: cytarabine, Drug: dexamethasone, Drug: methotrexate, Drug: pegaspargase, Drug: vincristine sulfatePatients receive oral dexamethasone twice daily on days 1-28; vincristine sulfate IV on days 1, 8, 15, and 22; pegaspargase intramuscularly (IM) on day 4, 5, or 6; cytarabine intrathecally (IT) on day 1; and methotrexate IT on day 8 (some patients also receive methotrexate IT on days 15 and 22). |
| Stratum 4 | Experimental | Drug: SC-PEG E. coli L-asparaginase, Drug: cytarabine, Drug: daunorubicin hydrochloride, Drug: methotrexate, Drug: prednisonePatients receive oral prednisone twice daily on days 1-28; vincristine sulfate IV on days 1, 8, 15, and 22; IM SC-PEG E. coli asparaginase on days 2, 5, 8, 12, 15, and 19; daunorubicin hydrochloride IV over 15-20 minutes on days 8, 15, and 22; and methotrexate IT on days 1 and 8 (some patients also receive methotrexate IT on days 15 and 22). |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
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 |
|---|---|---|
| SC-PEG E. coli L-asparaginaseGiven IM | Drug | Stratum 4 |
| cytarabineGiven IT | Drug | Stratum 3, Stratum 4 |
| daunorubicin hydrochlorideGiven IV | Drug | Stratum 4 |
| dexamethasoneGiven orally | Drug | Stratum 3 |
| methotrexateGiven IT | Drug | Stratum 3, Stratum 4 |
| pegaspargaseGiven IM | Drug | Stratum 3 |
| prednisoneGiven orally | Drug | Stratum 4 |
| vincristine sulfateGiven IV | Drug | Stratum 3 |
Primary outcome
Collection of the clinical and laboratory data necessary for placing patients with acute lymphoblastic leukemia (ALL) onto the proper therapeutic trial (Classification)
Creation of an administrative base to capture classification data for correlative studies in ALL treatment protocols and series of historical protocols (Classification)
Creation of appropriate induction regimens for patients (Induction therapy)
Correlation between event-free survival and measures of minimal-residual disease/early response
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 23 Feb 2016.
- Derived from this study: PubMed 38446568Escherich CS, Chen W, Li Y, Yang W, Nishii R, Li Z, Raetz EA, Devidas M, Wu G, Nichols KE, Inaba H, Pui CH, Jeha S, Camitta BM, Larsen E, Hunger SP, Loh ML, Yang JJ. Germ line genetic NBN variation and predisposition to B-cell acute lymphoblastic leukemia in children. Blood. 2024 May 30;143(22):2270-2283. doi: 10.1182/blood.2023023336.
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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.
Dale J. Pullen, MD study chair
University of Mississippi Cancer Clinic
Questions about this trial
What is this clinical trial studying?
A study testing SC-PEG E. coli L-asparaginase, cytarabine and daunorubicin hydrochloride in people with Leukemia, run by Children's Oncology Group.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 23 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
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?
Collection of the clinical and laboratory data necessary for placing patients with acute lymphoblastic leukemia (ALL) onto the proper therapeutic trial (Classification). The study lists 4 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 NCT01225874, 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 23 Feb 2016.