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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00005945




Registration number
NCT00005945
Ethics application status
Date submitted
5/07/2000
Date registered
27/01/2003
Date last updated
23/02/2016

Titles & IDs
Public title
Comparison of Different Combination Chemotherapy Regimens in Treating Children With Acute Lymphoblastic Leukemia
Scientific title
Escalating Dose Intravenous Methotrexate Without Leucovorin Rescue Versus Oral Methotrexate and Single Versus Double Delayed Intensification for Children With Standard Risk Acute Lymphoblastic Leukemia
Secondary ID [1] 0 0
CCG-1991
Secondary ID [2] 0 0
1991
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - cytarabine
Treatment: Drugs - daunorubicin hydrochloride
Treatment: Drugs - dexamethasone
Treatment: Drugs - doxorubicin hydrochloride
Treatment: Drugs - mercaptopurine
Treatment: Drugs - methotrexate
Treatment: Drugs - pegaspargase
Treatment: Drugs - thioguanine
Treatment: Drugs - vincristine sulfate
Treatment: Other - radiation therapy

Experimental: Induction Not Randomized - Standard Induction (28 Days). M3 Marrow at Day 28 and Off Protocol Therapy.

Experimental: Induction and Oral MTX, Double Delayed Intensification CNS - Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial radiation therapy during the Consolidation phase.

Experimental: Induction and Augmented regimen (IV MTX, Double DI) - Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses).

Experimental: Induction and Oral MTX, Single Delayed Intensification - Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.

Experimental: Induction and Oral MTX, Double Delayed Intensification - Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.

Experimental: Induction and IV MTX, Single Delayed Intensification - Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.

Experimental: Induction and IV MTX, Double Delayed Intensification - Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.


Treatment: Drugs: cyclophosphamide
Given IV

Treatment: Drugs: cytarabine
Given IT

Treatment: Drugs: daunorubicin hydrochloride
Given IV

Treatment: Drugs: dexamethasone
Given PO

Treatment: Drugs: doxorubicin hydrochloride
Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours

Treatment: Drugs: mercaptopurine
Given PO

Treatment: Drugs: methotrexate
Given PO and IT

Treatment: Drugs: pegaspargase
Given IM

Treatment: Drugs: thioguanine
Given PO

Treatment: Drugs: vincristine sulfate
Given IV

Treatment: Other: radiation therapy
Undergo radiation therapy
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event Free Survival
Timepoint [1] 0 0
Time of randomization

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

* Diagnosis of previously untreated B-cell precursor acute lymphoblastic leukemia

* More than 25% L1 or L2 lymphoblasts
* No more than 25% L3 lymphoblasts
* WBC < 50,000/mm^3
* No T-cell precursor acute lymphoblastic leukemia by immunophenotyping
* Massive lymphadenopathy, massive splenomegaly, or large mediastinal mass allowed
* CNS or testicular leukemia allowed
* No patients found to have t(8;14)(q24;q32), t(8;22)(q24;q11), and t(2;8)(p11-p12;q24) (characteristic of Burkitt's lymphoma)

PATIENT CHARACTERISTICS:

Age:

* 1 to 9

Performance status:

* Not specified

Life expectancy:

* Not specified

Hematopoietic:

* See Disease Characteristics

Hepatic:

* Not specified

Renal:

* Not specified

Other:

* Not pregnant
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No more than 72 hours since prior intrathecal cytarabine

Endocrine therapy:

* At least 30 days since prior systemic corticosteroids given for more than 48 hours
* Prior corticosteroids for mediastinal mass causing superior mediastinal syndrome allowed
* Prior or concurrent inhaled corticosteroids allowed

Radiotherapy:

* Prior radiotherapy for mediastinal mass causing superior mediastinal syndrome allowed
* No concurrent spinal radiotherapy

Surgery:

* Not specified
Minimum age
1 Year
Maximum age
9 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2000
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2008
Sample size
Target
Accrual to date
Final
3054
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
Royal Children's Hospital - Brisbane
Recruitment hospital [3] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4029 - Brisbane
Recruitment postcode(s) [3] 0 0
6001 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Delaware
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Idaho
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Indiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Iowa
Country [12] 0 0
United States of America
State/province [12] 0 0
Kentucky
Country [13] 0 0
United States of America
State/province [13] 0 0
Louisiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Maryland
Country [15] 0 0
United States of America
State/province [15] 0 0
Massachusetts
Country [16] 0 0
United States of America
State/province [16] 0 0
Michigan
Country [17] 0 0
United States of America
State/province [17] 0 0
Minnesota
Country [18] 0 0
United States of America
State/province [18] 0 0
Missouri
Country [19] 0 0
United States of America
State/province [19] 0 0
Nebraska
Country [20] 0 0
United States of America
State/province [20] 0 0
Nevada
Country [21] 0 0
United States of America
State/province [21] 0 0
New Jersey
Country [22] 0 0
United States of America
State/province [22] 0 0
New York
Country [23] 0 0
United States of America
State/province [23] 0 0
North Carolina
Country [24] 0 0
United States of America
State/province [24] 0 0
North Dakota
Country [25] 0 0
United States of America
State/province [25] 0 0
Ohio
Country [26] 0 0
United States of America
State/province [26] 0 0
Oregon
Country [27] 0 0
United States of America
State/province [27] 0 0
Pennsylvania
Country [28] 0 0
United States of America
State/province [28] 0 0
Rhode Island
Country [29] 0 0
United States of America
State/province [29] 0 0
South Dakota
Country [30] 0 0
United States of America
State/province [30] 0 0
Tennessee
Country [31] 0 0
United States of America
State/province [31] 0 0
Texas
Country [32] 0 0
United States of America
State/province [32] 0 0
Virginia
Country [33] 0 0
United States of America
State/province [33] 0 0
Washington
Country [34] 0 0
United States of America
State/province [34] 0 0
West Virginia
Country [35] 0 0
United States of America
State/province [35] 0 0
Wisconsin
Country [36] 0 0
Canada
State/province [36] 0 0
British Columbia
Country [37] 0 0
Canada
State/province [37] 0 0
Manitoba
Country [38] 0 0
Canada
State/province [38] 0 0
Newfoundland and Labrador
Country [39] 0 0
Canada
State/province [39] 0 0
Nova Scotia
Country [40] 0 0
Canada
State/province [40] 0 0
Ontario
Country [41] 0 0
Canada
State/province [41] 0 0
Saskatchewan
Country [42] 0 0
New Zealand
State/province [42] 0 0
Auckland
Country [43] 0 0
Switzerland
State/province [43] 0 0
Bern
Country [44] 0 0
Switzerland
State/province [44] 0 0
Geneva
Country [45] 0 0
Switzerland
State/province [45] 0 0
Lausanne

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating childhood acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is comparing different combination chemotherapy regimens to see how well they work in treating children with acute lymphoblastic leukemia.
Trial website
https://clinicaltrials.gov/study/NCT00005945
Trial related presentations / publications
Bruggers CS, Moyer-Mileur LJ, Ransdall L: Body composition, bone mineral acquisition, and cardiovascular fitness in children with standard risk acute lymphoblastic leukemia: response to a home-based exercise and nutrition education program. [Abstract] 2006 Pediatric Academic Societies' Annual Meeting, April 29 - May 2, San Francisco, CA. A-3505.46, 2006.
Matloub Y, Asselin BL, Stork LC, et al.: Outcome of children with T-Cell acute lymphoblastic leukemia (T-ALL) and standard risk (SR) features: results of CCG-1952, CCG-1991 and POG 9404. [Abstract] Blood 104 (11): A-680, 195a, 2004.
Fernandez CV, Kodish E, Taweel S, Shurin S, Weijer C; Children's Oncology Group. Disclosure of the right of research participants to receive research results: an analysis of consent forms in the Children's Oncology Group. Cancer. 2003 Jun 1;97(11):2904-9. doi: 10.1002/cncr.11391.
Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. doi: 10.1182/blood-2010-12-322909. Epub 2011 May 11.
Matloub Y, Bostrom BC, Angiolillo AL, et al.: Children with NCI standard risk acute lymphoblastic leukemia (ALL) and TEL-AML1 or favorable chromosome trisomies are almost certain to be cured with graduated intensity therapy: results of the CCG - 1991 study. [Abstract] Blood 114 (22): A-320, 2009.
Matloub Y, Bostrom BC, Hunger SP, et al.: Escalating dose intravenous methotrexate without leucovorin rescue during interim maintenance is superior to oral methotrexate for children with standard risk acute lymphoblastic leukemia (SR-ALL): Children's Oncology Group study 1991. [Abstract] Blood 112 (11): A-9, 2008.
Matloub Y, Angiolillo A, Bostrom B, et al.: Double delayed intensification (DDI) is equivalent to single DI (SDI) in children with National Cancer Institute (NCI) standard-risk acute lymphoblastic leukemia (SR-ALL) treated on Children's Cancer Group (CCG) clinical trial 1991 (CCG-1991). [Abstract] Blood 108 (11): A-146, 2006.
Matloub Y, Rabin KR, Ji L, Devidas M, Hitzler J, Xu X, Bostrom BC, Stork LC, Winick N, Gastier-Foster JM, Heerema NA, Stonerock E, Carroll WL, Hunger SP, Gaynon PS. Excellent long-term survival of children with Down syndrome and standard-risk ALL: a report from the Children's Oncology Group. Blood Adv. 2019 Jun 11;3(11):1647-1656. doi: 10.1182/bloodadvances.2019032094.
Public notes

Contacts
Principal investigator
Name 0 0
Yousif H. Matloub, MD
Address 0 0
University of Wisconsin, Madison
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00005945