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LeukemiaPhase 2NCT00558519

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

A Phase 2 study testing cyclophosphamide, cytarabine and daunorubicin hydrochloride in people with Leukemia, run by Alliance for Clinical Trials in Oncology.

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

RATIONALE: 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. Read more about this study

Who is it for?
Ages 16 to 39 years
Conditions the study is for
Leukemia
What is being tested?
cyclophosphamide, cytarabine and daunorubicin hydrochloride
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
318 participants
Where
No sites listed yet
Study dates
12 Mar 2008to 24 Jun 2024
Phase
Phase 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 16 to 39 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Eligibility Criteria:

  1. Diagnosis
  2. Newly diagnosed patients with either B-precursor or T-precursor acute lymphoblastic leukemia (WHO criteria). Burkitt type leukemia as defined per protocol is not eligible. Patients known to have Ph+ ALL at time of diagnosis are not eligible.
  3. CALGB patients entered on CALGB 10403 who are later found to meet the following criteria for Ph+ ALL should have treatment on this trial discontinued and should be encouraged to enroll on CALGB 10001 or its successor trial:
  • BCR-ABL fusion transcript determined by FISH or RT-PCR
  • t(9;22)(q34;q11) or variant determined by cytogenetics Non-CALGB study participants who are later found to be Ph+ should have treatment on this trial discontinued and should be encouraged to enroll on an appropriate clinical trial specifically designed for Ph+ ALL.
  1. Age: 16 - 39 years
  2. ECOG Performance Status 0-2
  3. Patients with Down Syndrome are excluded from this study due to the likelihood of excessive toxicity resulting. These patients should be treated in consultation with a pediatric oncologist.
  4. Prior Therapy - No prior therapy except for limited treatment with corticosteroids or hydroxyurea and a single dose of intrathecal cytarabine.
  5. No prior therapy for acute leukemia except emergency therapy (corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys. When indicated, leukapheresis or exchange transfusion is recommended to reduce the WBC.
  6. Single-dose intrathecal cytarabine is allowed prior to registration or prior to initiation of systemic therapy for patient convenience. This is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture. Systemic chemotherapy must begin within 72 hours of this intrathecal therapy.
  7. Patients receiving prior steroid therapy are eligible for study. The dose and duration of previous steroid therapy should be carefully documented on case report forms.

About this study

Official title: An Intergroup Phase II Clinical Trial for Adolescents and Young Adults With Untreated Acute Lymphoblastic Leukemia (ALL)

RATIONALE: 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 phase II trial is studying how well combination chemotherapy works in treating young patients with newly diagnosed acute lymphoblastic leukemia.

Read the detailed description

OUTLINE: This is a multicenter study. The purpose of this study is to improve the outcome of adolescents and young adults with acute lymphoblastic leukemia (ALL). The objectives of the study are described below.

OBJECTIVES:

  • To describe the outcomes (i.e., complete response rate, event-free survival, disease-free survival [DFS], and overall survival [OS]) of adolescents and young adults with newly diagnosed acute lymphoblastic leukemia (ALL) treated with a pediatric chemotherapy regimen by adult hematologists/oncologists at multiple sites.
  • To explore the feasibility of extending the "pediatric approach" to adult patients up to 40 years of age.
  • To estimate the DFS and OS of these patients.
  • To describe the toxicities observed in these patients.
  • To compare the outcomes of patients treated on this protocol with appropriate similar patients (by age and disease characteristics) treated by pediatric oncologists on protocol COG-AALL0232.
  • To evaluate the adherence of adult hematologists/oncologists and their patients to a "pediatric" ALL treatment regimen and identify reasons for variances.
  • To analyze and describe the outcomes of patients treated on this study according to pretreatment characteristics such as age, gender, white blood cell count, other hematologic parameters, blood chemistry, immunophenotype, cytogenetics and molecular genetic characteristics, and treatment variables such as treatment site (academic center or community), and protocol adherence.
  • To analyze and describe the outcomes of patients treated on this study according to baseline psychosocial characteristics, demographics, and family support.

The courses of treatment for the research study are described below.

  • Remission induction therapy: Patients receive intrathecal (IT) cytarabine on day 1; vincristine IV on days 1, 8, 15, and 22; prednisone IV or orally twice daily on days 1-28; daunorubicin hydrochloride IV on days 1, 8, 15, and 22; pegaspargase IV or intramuscularly (IM) on day 4 or 5 or 6; and IT methotrexate on days 8 and 29*. Patients undergo bone marrow aspirate (BMA) and biopsy on day 29 to assess induction response and minimal residual disease status. Patients with M1 marrow (< 1% lymphoblasts) proceed to remission consolidation therapy. Patients with M2 marrow (> 5% but < 25% lymphoblasts) proceed to extended remission induction therapy. Patients with M3 marrow are removed from protocol therapy.

NOTE: *Patients with CNS3 disease also receive IT methotrexate on days 15 and 22.

  • Extended remission induction therapy: Patients receive prednisone IV or orally twice daily on days 1-14; vincristine IV on days 1 and 8; pegaspargase IM or IV on day 4 or 5 or 6; and daunorubicin hydrochloride IV on day 1. Patients undergo BMA and biopsy on day 15. Patients with M1 marrow proceed to remission consolidation therapy. Patients with M2 or M3 bone marrow are removed from protocol therapy.
  • Remission consolidation therapy: Patients receive cyclophosphamide IV on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; oral mercaptopurine on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; pegaspargase IM or IV on days 15 and 43; and IT methotrexate on days 1, 8, 15*, and 22*. Once blood counts recover, patients proceed to interim maintenance therapy.

NOTE: *Patients with CNS3 disease do not receive IT methotrexate on days 15 and 22.

  • Interim maintenance therapy: Patients receive vincristine IV and methotrexate (Capizzi methotrexate) IV on days 1, 11, 21, 31, and 41; pegaspargase IM or IV on days 2 and 22; and IT methotrexate on days 1 and 31. Once blood counts recover (ANC ≥ 750/mm^3 and platelet count ≥ 75,000/mm^3), patients proceed to delayed intensification therapy.
  • Delayed intensification therapy: Patients receive vincristine IV on days 1, 8, 15, 43, and 50; dexamethasone IV or orally twice daily on days 1-7 and 15-21; doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV on day 4 or 5 or 6 AND day 43; cyclophosphamide IV on day 29; cytarabine IV or SC on days 29-32 and 36-39; oral thioguanine on days 29-42; and IT methotrexate on days 1, 29, and 36. Once blood counts recover, patients proceed to maintenance therapy.
  • Maintenance therapy: Patients receive vincristine IV on days 1, 29, and 57; dexamethasone IV or orally twice daily on days 1-5, 29-33, and 57-61; mercaptopurine orally on days 1-84; IT methotrexate on day 1*; and oral methotrexate on days 8, 15, 22, 29**, 36, 43, 50, 57, 64, 71, and 78.

Treatment repeats every 12 weeks for 2 years from the start of interim maintenance (for female patients) or 3 years from the start of interim maintenance (for male patients).

NOTE: *IT methotrexate is also given on day 29 of the first 4 courses of maintenance therapy.

NOTE: **Oral methotrexate is held on day 29 of the first 4 courses of maintenance therapy (when IT methotrexate is given).

  • Radiotherapy: During the first course of maintenance therapy, patients with testicular disease undergo concurrent radiotherapy to the testes 5 days a week for 2.5 weeks (total dose 2400 cGy given in 12 daily fractions); patients with CNS3 disease undergo concurrent cranial radiotherapy 5 days a week for 2 weeks (total dose of 1800 cGy given in 10 daily fractions); and patients with T-cell ALL undergo concurrent cranial radiotherapy (total dose of 2400 cGy given in 10 daily fractions) 5 days a week for 2 weeks.

Patients may complete surveys at the end of courses 1, 2, and 4, at the end of all protocol treatment, and at 6 and 18 months after the end of all protocol treatment.

After completion of study treatment, patients are followed every 1-3 months for 3 years and then every 6 months for 7 years.

Conditions
Leukemia
Being tested
cyclophosphamide, cytarabine, daunorubicin hydrochloride, dexamethasone, doxorubicin hydrochloride
Keywords
B-cell adult acute lymphoblastic leukemia, T-cell adult acute lymphoblastic leukemia, untreated adult 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.

Study groups in NCT00558519
Study groupRoleWhat they receive
Treatment (chemotherapy, radiotherapy)ExperimentalPatients are given a series of leukemia treatments that are divided into several sequential courses and different chemotherapy combinations of treatment. Please see the "Detailed Description" section for more information.
Receives: Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: dexamethasone; Drug: doxorubicin hydrochloride; Drug: mercaptopurine; Drug: methotrexate; Drug: pegaspargase; Drug: thioguanine; Drug: vincristine sulfate; Radiation: radiation therapy

What is being measured

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

  1. Complete Response Rate

    Complete response rate is defined as the percentage of patients who achieve bone marrow response (defined using the M bone marrow criteria for acute lymphoblastic leukemia (ALL); if M0 to M1 status (blast cells ,5%) was achieved by the end of induction or extended induction, the patient was considered a responder) at the end of induction therapy.

    Measured: Up to 8 years post-registration

  2. Event-free Survival

    EFS was defined as time from registration in this study to the earliest occurrence of any of the following: failure to achieve bone marrow response (defined using the M bone marrow criteria for acute lymphoblastic leukemia (ALL); if M0 to M1 status (blast cells ,5%) was achieved by the end of induction or extended induction, the patient was considered a responder) by day 60, death, relapse at any site, or development of second malignant disease.

    Measured: Up to 8 years post-registration

  3. Disease-free Survival

    DFS was defined as time from bone marrow response in this study to the earliest occurrence of any of the following: failure to achieve bone marrow response (defined using the M bone marrow criteria for acute lymphoblastic leukemia (ALL); if M0 to M1 status (blast cells ,5%) was achieved by the end of induction or extended induction, the patient was considered a responder) by day 60, death, relapse at any site, or development of second malignant disease.

    Measured: Up to 8 years post-registration

  4. Overall Survival

    OS was defined from registration to death resulting from any cause.

    Measured: Up to 8 years post-registration

  5. Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event at Least Possibly Related to Treatment (Toxicity)

    The number of participants who experienced toxicity (defined as at least one grade 3 or higher adverse event at least possibly related to treatment) is reported below.

    Measured: Up to 10 years post-registration

Timeline

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

  1. First posted15 Nov 2007 (estimated)
  2. Study start12 Mar 2008
  3. Primary completionSep 2016
  4. Study completion24 Jun 2024

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
318 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00558519
Sponsor's protocol ID
CALGB-10403
Other IDs
CALGB-10403, ECOG C10403, CDR0000574230
Status last verified
Apr 2026
First submitted
14 Nov 2007
Last updated
29 Apr 2026
Data monitoring committee
No

Publications

  • Bleyer A: Older adolescents and young adults with acute lymphoblastic leukemia (ALL) in the United States: from the lowest to highest death rate and number of deaths--more rationale for the CALBG-SWOG-ECOG C10403 trial based on COG AALL0232. [Abstract] J Clin Oncol 26 (Suppl 15): A-18034, 2008.

  • Advani AS, Larsen E, Laumann K, Luger SM, Liedtke M, Devidas M, Chen Z, Yin J, Foster MC, Claxton D, Coffan K, Tallman MS, Appelbaum FR, Erba H, Stone RM, Hunger SP, McNeer JL, Loh ML, Raetz E, Winick N, Carroll W, Larson RA, Stock W. Comparison of CALGB 10403 (Alliance) and COG AALL0232 toxicity results in young adults with acute lymphoblastic leukemia. Blood Adv. 2021 Jan 26;5(2):504-512. doi: 10.1182/bloodadvances.2020002439.

    PubMed 33496745

  • Stock W, Luger SM, Advani AS, Yin J, Harvey RC, Mullighan CG, Willman CL, Fulton N, Laumann KM, Malnassy G, Paietta E, Parker E, Geyer S, Mrozek K, Bloomfield CD, Sanford B, Marcucci G, Liedtke M, Claxton DF, Foster MC, Bogart JA, Grecula JC, Appelbaum FR, Erba H, Litzow MR, Tallman MS, Stone RM, Larson RA. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403. Blood. 2019 Apr 4;133(14):1548-1559. doi: 10.1182/blood-2018-10-881961. Epub 2019 Jan 18.

    PubMed 30658992

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cyclophosphamide, cytarabine and daunorubicin hydrochloride in people with Leukemia, run by Alliance for Clinical Trials in Oncology.

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 29 Apr 2026. 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.

What does this phase mean?

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 31 Jan 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?

Complete Response Rate (time frame: Up to 8 years post-registration). The study lists 5 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 NCT00558519, which also lists 3 linked publications.

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 29 Apr 2026.

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