Expired Study
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Arcadia, California 91006


Purpose:

Phase II trial to study the effectiveness of combining rituximab and rasburicase with combination chemotherapy in treating young patients who have newly diagnosed advanced B-cell leukemia or lymphoma. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug with rituximab may kill more cancer cells. Chemoprotective drugs such as rasburicase may protect kidney cells from the side effects of chemotherapy.


Study summary:

OBJECTIVES: I. Determine the toxicity of the addition of rituximab to induction chemotherapy comprising vincristine, methylprednisolone, methotrexate, leucovorin calcium, cyclophosphamide, and doxorubicin (COPADM) [COMRAP] and to consolidation chemotherapy in children with newly diagnosed FAB prognostic group B or group C leukemia or lymphoma treated with LMB/FAB therapy. II. Determine the toxicity of the addition of rasburicase to the reduction phase comprising cyclophosphamide, vincristine, prednisone or methylprednisolone, methotrexate, and leucovorin calcium (COP-R) in these patients. III. Determine the incidence of tumor lysis syndrome, renal complications, and the use of assisted renal support (i.e., dialysis or hemofiltration) during the COP-R reduction phase and the first induction phase of COPADM or COMRAP in these patients. IV. Determine the response rate of patients treated with COMRAP incorporated into LMB/FAB therapy. V. Assess minimal residual disease in patients before and during COMRAP therapy incorporated into LMB/FAB therapy. OUTLINE: This is a multicenter study. Patients are stratified according to FAB prognostic group (B vs C) and treated by group classification. FAB GROUP B TREATMENT I (first 6 patients): REDUCTION THERAPY: Patients receive the COP-R regimen comprising cyclophosphamide IV over 15 minutes, vincristine IV, and methotrexate and hydrocortisone intrathecally (IT) on day 0; rasburicase* IV over 30 minutes every 12 hours on days 0 and 1 and then once daily on days 2-4 (patients exhibiting hyperuricemia and clinical suspicion of B-cell non-Hodgkin's lymphoma or B-cell acute lymphocytic leukemia also receive rasburicase on days -3, -2, and -1); leucovorin calcium IV or orally every 12 hours on days 1 and 3; and prednisone (PRED) or methylprednisolone (MePRDL) IV (or orally) on days 0-6. Patients too critical to proceed may receive another course of reduction therapy. NOTE: *Patients with G6PD deficiency do not receive rasburicase during reduction therapy. INDUCTION THERAPY: Patients with less than 20% tumor reduction follow the group C induction phase (described below). Patients with at least 20% tumor reduction receive 1 course of the COPADM regimen: vincristine IV and methotrexate IV over 4 hours on day 0; PRED or MePRDL IV (or orally) on days 0-7; leucovorin calcium IV or orally every 6 hours for 12 doses on days 1-3; doxorubicin IV over 30-60 minutes on day 1; cyclophosphamide IV over 15 minutes every 12 hours on days 1-3; methotrexate IT and hydrocortisone IT on days 1 and 5; and filgrastim (G-CSF) subcutaneously (SC) beginning on day 6 and continuing until blood counts recover. Patients receive the second part of induction therapy when peripheral blood counts have recovered but no fewer than 16 days after the first part of induction therapy. Patients receive 1 course of the COMRAP regimen comprising rituximab IV on days -2 and 0 with COPADM as in the first part of induction therapy. CONSOLIDATION THERAPY: Patients receive the CYM-RM regimen comprising rituximab IV and methotrexate IV over 4 hours on day 0; leucovorin calcium IV or orally every 6 hours for 12 doses on days 1-3; cytarabine IV over 24 hours daily on days 1-5; hydrocortisone IT on days 1 and 6; methotrexate IT on day 1; and cytarabine IT on day 6. After full recovery from consolidation therapy, patients with any residual masses undergo surgical excision or biopsy. Patients with histology positive for tumor (even if completely resected) proceed to Group C consolidation therapy (described below). Patients with histology negative for tumor proceed to Group B maintenance therapy. MAINTENANCE THERAPY: Patients receive the COPADM regimen comprising vincristine IV and methotrexate IV over 4 hours on day 0; PRED or MePRDL IV (or orally) on days 0-7; doxorubicin IV over 30-60 minutes, and cyclophosphamide IV over 30 minutes on days 1 and 2; methotrexate IT and hydrocortisone IT on day 1; and leucovorin calcium IV or orally every 6 hours on days 1-3 (12 doses). TREATMENT II (44 patients): REDUCTION THERAPY: Patients receive the COP-R regimen as in treatment I. INDUCTION THERAPY: Patients receive 2 courses of the COMRAP regimen as in the second induction of treatment I. CONSOLIDATION THERAPY: Patients receive the CYM-RM regimen as in treatment I. MAINTENANCE THERAPY: Patients receive the COPADM regimen as in treatment I. FAB GROUP C: TREATMENT I (first 3 patients): REDUCTION THERAPY: Patients receive the COP-R regimen as in group B treatment I, with the addition of triple intrathecal therapy (TIT) comprising methotrexate, hydrocortisone, and cytarabine on days 0, 2, and 4. INDUCTION THERAPY: Patients receive 2 courses of the COPADM regimen as in group B treatment I, with the addition of TIT on days 1, 3, and 5. Patients in group C who have biopsy-proven disease after induction therapy are off protocol therapy and treated at the discretion of the investigator. CONSOLIDATION THERAPY: CNS-POSITIVE DISEASE: Patients receive 2 courses of the CYVE-RM regimen comprising rituximab IV and methotrexate and hydrocortisone IT on day 0; cytarabine IV over 12 hours on days 0-4; high-dose cytarabine IV over 3 hours and etoposide IV over 2 hours on days 1-4; and G-CSF SC on days 6-20. During the first course, patients also receive HD-MTX IV over 4 hours on day 17; TIT on day 18; and leucovorin calcium IV or orally every 6 hours on days 18-21 (12 doses). CNS-NEGATIVE DISEASE: Patients receive the CYVE-RM regimen without intrathecal therapy, HD-MTX, or leucovorin calcium. After full recovery from consolidation therapy, patients with any residual masses undergo surgical excision or biopsy. Patients who do not achieve complete remission after consolidation therapy are considered treatment failures. MAINTENANCE THERAPY (each course lasts 28 days): COURSE M1: Patients receive vincristine IV and high-dose methotrexate IV over 4 hours on day 0; PRED or MePRDL IV (or orally) on days 0-7; doxorubicin IV over 30-60 minutes and TIT on day 1; cyclophosphamide IV over 30 minutes on days 1 and 2; and leucovorin calcium IV or orally every 6 hours on days 1-4 (12 doses). COURSE M2: Patients receive etoposide IV over 90 minutes on days 0-2 and cytarabine SC every 12 hours on days 0-4. COURSE M3: Patients receive vincristine IV on day 0; cyclophosphamide IV over 30 minutes on days 0 and 1; PRED or MePRDL IV (or orally) twice daily on days 0-7; and doxorubicin IV over 30-60 minutes on day 0 (after first dose of cyclophosphamide). COURSE M4: Patients receive etoposide and cytarabine as in course M2. TREATMENT II (37 patients): REDUCTION THERAPY: Patients receive 2 courses of the COP-R regimen as in group C treatment I. INDUCTION THERAPY: Patients receive the COMRAP regimen comprising rituximab IV, vincristine IV, and HD-MTX IV over 4 hours on day 0; PRED or MePRDL IV (or orally) on days 0-7; leucovorin calcium IV or orally and cyclophosphamide IV over 15 minutes on days 1-3; doxorubicin IV over 30-60 minutes on day 1; TIT on days 1, 3, and 5; and G-CSF SC on days 6-20. CONSOLIDATION THERAPY: CNS-positive disease: Patients receive the CYVE-RM regimen plus HD-MTX as in group C treatment I. Patients then receive CYVE-RM for a second course. CNS-NEGATIVE DISEASE: Patients receive CYVE-RM regimen as in group C treatment I. MAINTENANCE THERAPY: Patients receive maintenance therapy as in group C treatment I. Patients are followed every 3-6 months for 1 year and then every 6 months for up to 5 years


Criteria:

Inclusion Criteria: - Newly diagnosed mature B-lineage (CD20-positive) leukemia or lymphoma by the REAL classification of 1 of the following subtypes: - Diffuse large cell lymphoma - Burkitt's lymphoma - High-grade B-cell lymphoma (Burkitt-like) - No B-cell anaplastic large cell Ki-1 positive lymphomas and B-lymphoblastic lymphomas - One of the following FAB prognostic groups: - Group B (intermediate risk) - Group C (high risk) - Bone marrow involvement with at least 25% blasts and/or CNS involvement meeting 1 or more of the following criteria: - Any L3 blasts in cerebrospinal fluid - Cranial nerve palsy (if not explained by extracranial tumor) - Clinical spinal cord compression - Isolated intracerebral mass - Parameningeal extension (cranial and/or spinal) - Hepatitis B status known - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 6 months after study participation - No known history of congenital immune deficiency and/or laboratory evidence of acquired immune deficiency - No known G6PD deficiency (if receiving rasburicase) - No prior malignancies treated with systemic chemotherapy with alkylator or anthracycline therapy - No prior chemotherapy - At least 1 week since prior steroids except emergency steroids initiated within 72 hours of study entry - No prior radiotherapy except emergency radiotherapy initiated within 72 hours of study entry - No concurrent radiotherapy - No prior solid organ transplantation


Study is Available At:


Original ID:

ANHL01P1


NCT ID:

NCT00057811


Secondary ID:

NCI-2009-00405


Study Acronym:


Brief Title:

Rituximab, Rasburicase, and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Advanced B-Cell Leukemia or Lymphoma


Official Title:

A Pilot Study To Determine The Toxicity Of The Addition Of Rituximab To The Induction And Consolidation Phases And The Addition Of Rasburicase To The Reduction Phase In Children With Newly Diagnosed Advanced B-Cell Leukemia/Lymphoma Treated With LMB/FAB T


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

1 Year


Maximum Age:

29 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Children's Oncology Group


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Non-Randomized, Endpoint Classificati


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

97


Enrollment Type:

Actual


Overall Contact Information

Official Name:Mitchell Cairo
Principal Investigator
Children's Oncology Group

Study Dates

Start Date:June 2004
Primary Completion Date:October 2009
Primary Completion Type:Actual
Verification Date:June 2013
Last Changed Date:June 11, 2013
First Received Date:April 7, 2003

Study Outcomes

Outcome Type:Primary Outcome
Measure:Response rate
Time Frame:Up to 5 years
Safety Issues:False
Description:Confidence intervals will be constructed for the proportion of patients who achieve at least a partial response prior to beginning consolidation. No correction for multiple comparisons will be made in these computations.
Outcome Type:Primary Outcome
Measure:Minimal residual disease
Time Frame:Not Provided
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Toxicity rate of rituximab using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v. 3.0
Time Frame:Up to 1 year
Safety Issues:True
Description:Two events are of particular interest, the incidence of grade ≥ 3 stomatitis and any occurrence of a toxic death. For the implementation of the toxic death rate stopping rule, a death must be possibly, probably or definitely attributable to rituximab and/

Study Interventions

Intervention Type:Drug
Name:doxorubicin hydrochloride
Description:Given IV, IT, or orally
Arm Name:Group B (chemotherapy, protective therapy, monoclo
Other Name:ADM
Intervention Type:Drug
Name:cyclophosphamide
Description:Given IV
Arm Name:Group B (chemotherapy, protective therapy, monoclo
Other Name:CPM
Intervention Type:Drug
Name:methotrexate
Description:Given IV or IT
Arm Name:Group B (chemotherapy, protective therapy, monoclo
Other Name:amethopterin
Intervention Type:Drug
Name:rasburicase
Description:Given IV
Arm Name:Group B (chemotherapy, protective therapy, monoclo
Other Name:Elitek
Intervention Type:Drug
Name:leucovorin calcium
Description:Given IV or orally
Arm Name:Group B (chemotherapy, protective therapy, monoclo
Other Name:CF
Intervention Type:Drug
Name:prednisone
Description:Given IV or orally
Arm Name:Group B (chemotherapy, protective therapy, monoclo
Other Name:DeCortin
Intervention Type:Drug
Name:methylprednisolone
Description:Given IV or orally
Arm Name:Group B (chemotherapy, protective therapy, monoclo
Other Name:Depo-Medrol
Intervention Type:Biological
Name:filgrastim
Description:Given subcutaneously
Arm Name:Group B (chemotherapy, protective therapy, monoclo
Other Name:G-CSF
Intervention Type:Biological
Name:rituximab
Description:Given IV
Arm Name:Group B (chemotherapy, protective therapy, monoclo
Other Name:IDEC-C2B8
Intervention Type:Drug
Name:cytarabine
Description:Given IT
Arm Name:Group B (chemotherapy, protective therapy, monoclo
Other Name:ARA-C
Intervention Type:Drug
Name:etoposide
Description:Given IV
Arm Name:Group C (Chemotherapy, monoclonal antibody therapy
Other Name:EPEG
Intervention Type:Drug
Name:vincristine sulfate
Description:Given IV
Arm Name:Group B (chemotherapy, protective therapy, monoclo
Other Name:leurocristine sulfate
Intervention Type:Drug
Name:hydrocortisone sodium succinate
Description:Given IT
Arm Name:Group B (chemotherapy, protective therapy, monoclo
Other Name:Sodium hydrocortisone succinate
Intervention Type:Other
Name:laboratory biomarker analysis
Description:Correlative studies
Arm Name:Group B (chemotherapy, protective therapy, monoclo

Study Arms

Study Arm Type:Experimental
Arm Name:Group B (chemotherapy, protective therapy, monoclonal antib.)
Description:Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
Study Arm Type:Experimental
Arm Name:Group C (Chemotherapy, monoclonal antibody therapy))
Description:Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Children's Oncology Group
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation:Cairo MS, Lynch J, Harrison L, et al.: Safety, efficacy and rituximab levels following chemoimmunotherapy (rituximab + FAB chemotherapy) in children and adolescents with mature B-cell Non-Hodgkin lymphoma (B-NHL): a Children's Oncology Group report. [Abstract] Blood 112 (11): A-838, 2008.
Reference Type:Results Reference
Citation:Goldman S, Lynch J, Harrison L, et al.: Preliminary results of the addition of rasburicase to the reduction cycle and rituximab to the induction and consolidation cycles of FAB group C chemotherapy in children and adolescents with advanced stage (bone marrow ±CNS) mature B-cell non-Hodgkin lymphoma (B-NHL): A Children's Oncology Group report . [Abstract] Blood 114 (22): A-104, 2009.
Reference Type:Results Reference
Citation:Goldman S, Smith L, Anderson JR, Perkins S, Harrison L, Geyer MB, Gross TG, Weinstein H, Bergeron S, Shiramizu B, Sanger W, Barth M, Zhi J, Cairo MS. Rituximab and FAB/LMB 96 chemotherapy in children with Stage III/IV B-cell non-Hodgkin lymphoma: a Children's Oncology Group report. Leukemia. 2012 Sep 3. doi: 10.1038/leu.2012.255. [Epub ahead of print]
PMID:22940833

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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