AzTrials
AzTrials

LeukemiaPhase 3NCT00005603

Combination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia

A Phase 3 study testing asparaginase, cyclophosphamide and cytarabine in people with Leukemia, run by Children's Oncology Group at 20 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

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective for acute lymphoblastic leukemia. Read more about this study

Who is it for?
Ages 1 year to 21 years
Conditions the study is for
Leukemia
What is being tested?
asparaginase, cyclophosphamide and cytarabine
How many people
276 participants
Where
20 sitesUnited States
Study dates
Mar 2000to Sep 2005
Phase
Phase 3
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

DISEASE CHARACTERISTICS:

  • Diagnosis of B-cell precursor acute lymphoblastic leukemia
  • Registered on POG-9900 Classification Study
  • Registered within 7 days of documenting complete response after induction on day 29 or, if 2 more weeks of induction are required, no later than day 49
  • Classified as high risk:
  • No simultaneous trisomy 4 and 10
  • No TEL-AML1 gene
  • Meets criteria for 1 of the following:
  • Any age with WBC > 100,000/mm^3
  • CNS and bone marrow evaluations required for those patients with WBC > 100,000/mm^3 who are within 24 months of initial diagnosis
  • Age over 12 (boys) or 16 (girls)
  • If younger, WBC must be 1 of the following:
  • Greater than 80,000/mm^3 (for boys age 8 or girls age 12)
  • Greater than 60,000/mm^3 (for boys age 9 or girls age 13)
  • Greater than 40,000/mm^3 (for boys age 10 or girls age 14)
  • Greater than 20,000/mm^3 (for boys age 11 or girls age 15)
  • At least one of the following:
  • CNS 3 disease (CSF WBC at least 5/microliter with blasts present)
  • Testicular leukemia
  • MLL gene rearrangements

PATIENT CHARACTERISTICS:

Age:

  • 1 to 21

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Not specified

Renal:

  • Not specified

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • See Disease Characteristics

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

Other:

  • See Disease Characteristics

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

United States20 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Children's Hospital Medical Center - Cincinnati

    Cincinnati, Ohio, 45229-3039

  • University of Texas Medical Branch

    Galveston, Texas, 77555-0361

  • University of Texas - MD Anderson Cancer Center

    Houston, Texas, 77030-4009

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Indiana University Cancer Center

    Indianapolis, Indiana, 46202-5289

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216-4505

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027-0700

  • Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Lucile Packard Children's Hospital at Stanford

    Palo Alto, California, 94304

  • Saint Jude Midwest Affiliate

    Peoria, Illinois, 61637

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Doernbecher Children's Hospital

    Portland, Oregon, 97201-3098

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • UCSF Comprehensive Cancer Center

    San Francisco, California, 94143-0128

  • Children's Hospital and Regional Medical Center - Seattle

    Seattle, Washington, 98105

  • State University of New York - Upstate Medical University

    Syracuse, New York, 13210

  • Albert Einstein Clinical Cancer Center

    The Bronx, New York, 10461

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010-2970

Other trials in United States

About this study

Official title: ALinC 17: Protocol for Patients With Newly Diagnosed High Risk Acute Lymphoblastic Leukemia (ALL) - Evaluation of the Augmented BFM Regimen: A Phase III Study

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective for acute lymphoblastic leukemia.

PURPOSE: Phase III trial to determine the effectiveness of combination chemotherapy in treating children who have newly diagnosed acute lymphoblastic leukemia.

Read the detailed description

OBJECTIVES:

  • Determine whether augmented BFM therapy is superior to ALinc 14/15 therapy in patients with newly diagnosed high-risk acute lymphoblastic leukemia.
  • Determine whether minimal residual disease after induction therapy is predictive of an inferior prognosis in this patient population.
  • Determine the correlation between event-free survival, minimal residual disease, and early response in this patient population treated with this multiple drug regimen.

OUTLINE: Patients are stratified by CNS or testicular disease (yes vs no).

  • Induction therapy (weeks 1-5): Patients receive oral prednisone 3 times daily on days 1-29; vincristine IV on days 1, 8, 15, and 22; daunorubicin IV on days 8, 15, 22; and asparaginase intramuscularly (IM) on days 2, 5, 8, 12, 15, and 19. Patients also receive methotrexate intrathecally (IT) on days 1 and 8. Patients with CNS 2 or 3 disease also receive methotrexate IT on days 15 and 22.

Patients with M1 bone marrow proceed to consolidation therapy. Patients achieving M2 bone marrow on day 29 receive oral prednisone 3 times daily on days 29-42; vincristine IV and daunorubicin IV over 15 minutes on days 29 and 36; and asparaginase IM on days 29, 32, 36, and 39. If bone marrow is M3 on day 29 or M2 on day 43, then patient is off study.

  • Consolidation therapy (weeks 6-14): Patients receive cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine subcutaneously (SC) or IV on days 2-5, 9-12, 30-33, and 37-40; oral mercaptopurine daily on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; asparaginase IM on days 15, 17, 19, 22, 24, 26, 43, 45, 47, 50, 52, and 54; and methotrexate IT on days 1, 15, 29, and 43.

Patients then proceed to interim maintenance and delayed intensification on weeks 15-46. Courses repeat every 16 weeks.

  • Maintenance I and II (weeks 15-22 and 31-38): Patients receive vincristine IV and methotrexate IV on days 1, 11, 21, 31, and 41; asparaginase IM on days 2, 12, 22, 32, and 42; and methotrexate IT on days 1 and 31.
  • Delayed Intensification (weeks 23-36 and 39-42): Patients receive vincristine IV on days 57, 64, and 71; methotrexate IT on day 57; oral dexamethasone 2-3 times daily on days 57-63 and 71-77; doxorubicin IV over 15 minutes 3 times weekly on days 57, 64, and 71; and asparaginase IM on days 60, 62, 64, 67, 69, and 71.
  • Delayed Intensification-Reconsolidation (weeks 27-30 and 43-46): Patients receive oral thioguanine on days 85-98; methotrexate IT on day 85; cyclophosphamide IV over 30 minutes on day 85; cytarabine IV or SC on days 86-89 and 93-96; asparaginase IM on days 99, 101, 103, 106, 108, and 110; and vincristine IV on days 99 and 106.
  • Continuation therapy (weeks 47-130): Patients receive vincristine IV on days 1, 29, and 57; oral dexamethasone twice daily for 5 consecutive days on days 1-5, 29-33, and 57-61; oral mercaptopurine on days 1-84; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1.

Patients with CNS 3 disease or who are within 24 months of diagnosis with an initial WBC ≥ 100,000/mm^3 undergo whole brain radiotherapy (omit or discontinue mercaptopurine and IT methotrexate) on day 1. Testicular radiotherapy also begins on day 1.

Patients may receive oral methotrexate on day 1 of each course (if IT methotrexate is not administered).

Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 260 patients will be accrued for this study within 3.1 years.

Conditions
Leukemia
Being tested
asparaginase, cyclophosphamide, cytarabine, daunorubicin hydrochloride, dexamethasone
Keywords
childhood acute lymphoblastic leukemia in remission, B-cell 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.

What is being measured

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

  1. Augmented Berlin Frankfurt Muenster (BFM) therapy is superior to ALinC 14/15 therapy

    To determine for patients at high risk for treatment failure if the augmented Berlin Frankfurt Muenster (BFM) therapy is superior to ALinC 14/15 therapy, on the basis of historical controls.

Timeline

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

  1. First posted27 Jan 2003 (estimated)
  2. Study startMar 2000
  3. Primary completionSep 2005

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 3
Primary purpose
Treatment
Masking
None (open label)
Enrolment
276 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00005603
Sponsor's protocol ID
9906
Other IDs
COG-P9906, POG-9906, CDR0000067722
Status last verified
Feb 2014
First submitted
2 May 2000
Last updated
20 Feb 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Chen IM, Harvey RC, Mullighan CG, Gastier-Foster J, Wharton W, Kang H, Borowitz MJ, Camitta BM, Carroll AJ, Devidas M, Pullen DJ, Payne-Turner D, Tasian SK, Reshmi S, Cottrell CE, Reaman GH, Bowman WP, Carroll WL, Loh ML, Winick NJ, Hunger SP, Willman CL. Outcome modeling with CRLF2, IKZF1, JAK, and minimal residual disease in pediatric acute lymphoblastic leukemia: a Children's Oncology Group study. Blood. 2012 Apr 12;119(15):3512-22. doi: 10.1182/blood-2011-11-394221. Epub 2012 Feb 24.

    PubMed 22368272

  • Rabin KR, Gramatges MM, Borowitz MJ, Palla SL, Shi X, Margolin JF, Zweidler-McKay PA. Absolute lymphocyte counts refine minimal residual disease-based risk stratification in childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2012 Sep;59(3):468-74. doi: 10.1002/pbc.23395. Epub 2011 Nov 18.

    PubMed 22102553

  • Yang JJ, Cheng C, Yang W, Pei D, Cao X, Fan Y, Pounds SB, Neale G, Trevino LR, French D, Campana D, Downing JR, Evans WE, Pui CH, Devidas M, Bowman WP, Camitta BM, Willman CL, Davies SM, Borowitz MJ, Carroll WL, Hunger SP, Relling MV. Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia. JAMA. 2009 Jan 28;301(4):393-403. doi: 10.1001/jama.2009.7.

    PubMed 19176441

  • Borowitz MJ, Devidas M, Hunger SP, et al.: Prognostic signficance of end consolidation minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group (COG). [Abstract] J Clin Oncol 26 (Suppl 15): A-10000, 2008.

  • Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL, Linda S, Martin PL, Pullen DJ, Viswanatha D, Willman CL, Winick N, Camitta BM; Children's Oncology Group. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study. Blood. 2008 Jun 15;111(12):5477-85. doi: 10.1182/blood-2008-01-132837. Epub 2008 Apr 3.

    PubMed 18388178

  • Davies SM, Borowitz MJ, Rosner GL, Ritz K, Devidas M, Winick N, Martin PL, Bowman P, Elliott J, Willman C, Das S, Cook EH, Relling MV. Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2008 Mar 15;111(6):2984-90. doi: 10.1182/blood-2007-09-114082. Epub 2008 Jan 8.

    PubMed 18182569

  • Harvey RC, Mullighan CG, Wang X, Dobbin KK, Davidson GS, Bedrick EJ, Chen IM, Atlas SR, Kang H, Ar K, Wilson CS, Wharton W, Murphy M, Devidas M, Carroll AJ, Borowitz MJ, Bowman WP, Downing JR, Relling M, Yang J, Bhojwani D, Carroll WL, Camitta B, Reaman GH, Smith M, Hunger SP, Willman CL. Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome. Blood. 2010 Dec 2;116(23):4874-84. doi: 10.1182/blood-2009-08-239681. Epub 2010 Aug 10.

    PubMed 20699438

  • Yang JJ, Yang W, Cheng C, et al.: Genetically defined racial differences underlie risk of relapse in childhood acute lymphoblastic leukemia. [Abstract] Blood 112 (11): A-14, 2008.

  • Bowman WP, Larsen EL, Devidas M, Linda SB, Blach L, Carroll AJ, Carroll WL, Pullen DJ, Shuster J, Willman CL, Winick N, Camitta BM, Hunger SP, Borowitz MJ. Augmented therapy improves outcome for pediatric high risk acute lymphocytic leukemia: results of Children's Oncology Group trial P9906. Pediatr Blood Cancer. 2011 Oct;57(4):569-77. doi: 10.1002/pbc.22944. Epub 2011 Feb 25.

    PubMed 21360654

  • Zhang J, Mullighan CG, Harvey RC, Wu G, Chen X, Edmonson M, Buetow KH, Carroll WL, Chen IM, Devidas M, Gerhard DS, Loh ML, Reaman GH, Relling MV, Camitta BM, Bowman WP, Smith MA, Willman CL, Downing JR, Hunger SP. Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Sep 15;118(11):3080-7. doi: 10.1182/blood-2011-03-341412. Epub 2011 Jun 16.

    PubMed 21680795

  • Harvey RC, Mullighan CG, Chen IM, Wharton W, Mikhail FM, Carroll AJ, Kang H, Liu W, Dobbin KK, Smith MA, Carroll WL, Devidas M, Bowman WP, Camitta BM, Reaman GH, Hunger SP, Downing JR, Willman CL. Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia. Blood. 2010 Jul 1;115(26):5312-21. doi: 10.1182/blood-2009-09-245944. Epub 2010 Feb 4.

    PubMed 20139093

  • Kang H, Chen IM, Wilson CS, Bedrick EJ, Harvey RC, Atlas SR, Devidas M, Mullighan CG, Wang X, Murphy M, Ar K, Wharton W, Borowitz MJ, Bowman WP, Bhojwani D, Carroll WL, Camitta BM, Reaman GH, Smith MA, Downing JR, Hunger SP, Willman CL. Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia. Blood. 2010 Feb 18;115(7):1394-405. doi: 10.1182/blood-2009-05-218560. Epub 2009 Oct 30.

    PubMed 19880498

  • Mullighan CG, Morin R, Zhang J, et al.: Next generation transcriptomic resequencing identifies novel genetic alterations in high-risk (HR) childhood acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group (COG) HR ALL TARGET Project. [Abstract] Blood 114 (22): A-704, 2009.

  • Zhang J, Mullighan CG, Harvey RC, et al.: Mutations in the RAS signaling, B-cell development, TP53/RB1, and JAK signaling pathways are common in high risk B-precursor childhood acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group (COG) High-Risk (HR) ALL TARGET Project. [Abstract] Blood 114 (22): A-85, 2009.

  • Harvey RC, Davidson GS, Wang X, et al.: Expression profiling identifies novel genetic subgroups with distinct clinical features and outcome in high-risk pediatric precursor B acute lymphoblastic leukemia (B-ALL). A Children's Oncology Group study. [Abstract] Blood 110 (11): A-1430, 2007.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing asparaginase, cyclophosphamide and cytarabine in people with Leukemia, run by Children's Oncology Group at 20 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?

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 20 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 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 phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Augmented Berlin Frankfurt Muenster (BFM) therapy is superior to ALinC 14/15 therapy. 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 NCT00005603, which also lists 19 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 20 Feb 2014.

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