Combination Chemotherapy With or Without Rituximab in Treating Younger Patients With Stage III-IV Non-Hodgkin Lymphoma or B-Cell Acute Leukemia - Full Text View

Purpose

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. Monoclonal antibody, such as rituximab, can block cancer cells growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether giving combination chemotherapy together with rituximab is more effective in treating patients with non-Hodgkin lymphoma or B-cell acute leukemia.

PURPOSE: This randomized phase II/III trial studies how well giving combination chemotherapy with or without rituximab works in treating younger patients with stage III or stage IV non-Hodgkin lymphoma or B-cell acute leukemia.

Condition	Intervention	Phase
Leukemia Lymphoma	Biological: rituximab Drug: cyclophosphamide Drug: cytarabine Drug: doxorubicin hydrochloride Drug: etoposide Drug: hydrocortisone sodium succinate Drug: leucovorin calcium Drug: methotrexate Drug: methylprednisolone Drug: prednisone Drug: vincristine sulfate	Phase 2 Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Open Label Primary Purpose: Treatment
Official Title:	Intergroup Trial for Children or Adolescents With B-Cell NHL or B-AL: Evaluation of Rituximab Efficacy and Safety in High Risk Patients

Resource links provided by NLM:

MedlinePlus related topics: Calcium Cancer Chronic Lymphocytic Leukemia Leukemia Lymphoma Steroids

Drug Information available for: Hydrocortisone acetate Cyclophosphamide Hydrocortisone Prednisolone Prednisolone acetate Prednisone Methylprednisolone acetate Methotrexate Methylprednisolone Succinic acid Prednisolone sodium phosphate Hydrocortisone sodium succinate Cytarabine Calcium Gluconate Prednisolone phosphate Hydrocortisone cypionate Leucovorin calcium Prednisolone sodium succinate Vincristine sulfate Methylprednisolone sodium succinate Hydrocortisone butyrate Sodium succinate Sulfate ion Methotrexate sodium Doxorubicin Doxorubicin hydrochloride Etoposide Hydrocortisone valerate Levoleucovorin Hydrocortisone probutate Etoposide phosphate Rituximab

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

EFS at 3 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Survival estimated by the Kaplan-Meier method and the 95% confidence intervals (95% CI) of the actuarial rates calculated by the Rothman method [ Designated as safety issue: No ]
Complete remission rate compared between arms by logistic regression [ Designated as safety issue: No ]
Acute and long-term toxicity as assessed by the National Cancer Institute Common Terminology Criteria version 4.0 [ Designated as safety issue: Yes ]
Immune reconstitution as assessed by Ig (G, A, and M) levels and lymphocyte counts [ Designated as safety issue: No ]

Estimated Enrollment:	640
Study Start Date:	June 2012
Estimated Primary Completion Date:	December 2020 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Group 1 Patients receive vincristine sulfate IV on day 1; cyclophosphamide IV over 15 minutes on day 1; prednisone PO BID or methylprednisolone IV on days 1-7; methotrexate intrathecally (IT) and hydrocortisone IT on day 1. Patients are randomized to 1 of 2 treatment arms.	Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: hydrocortisone sodium succinate Given IT Drug: methotrexate Given IV Drug: methylprednisolone Given IV Drug: prednisone Given PO Drug: vincristine sulfate Given IV
Experimental: Arm I Beginning 8 days later, patients receive rituximab IV on day 1; vincristine sulfate IV on day 1; prednisone PO BID or methylprednisolone IV on days 1-5; methotrexate IV over 3 hours on day 1; leucovorin calcium PO every 6 hours on days 2-4; cyclophosphamide IV over 15 minutes on days 2-4; doxorubicin hydrochloride over 1 hour on day 2; and methotrexate IT and hydrocortisone IT on days 2 and 6. Treatment repeats every 18-21 days for 2 courses.	Biological: rituximab Given IV Drug: cyclophosphamide Given IV Drug: cytarabine Given IV Drug: doxorubicin hydrochloride Given IV Drug: hydrocortisone sodium succinate Given IT Drug: leucovorin calcium Given PO Drug: methotrexate Given IV Drug: methylprednisolone Given IV Drug: prednisone Given PO Drug: vincristine sulfate Given IV
Active Comparator: Arm II Beginning 8 days later, patients receive vincristine sulfate, prednisone or methylprednisolone, methotrexate, leucovorin calcium, cyclophosphamide, doxorubicin, methotrexate IT, and hydrocortisone IT as in arm I. Treatment repeats every 18-21 days for 2 courses.	Drug: cyclophosphamide Given IV Drug: cytarabine Given IV Drug: doxorubicin hydrochloride Given IV Drug: hydrocortisone sodium succinate Given IT Drug: leucovorin calcium Given PO Drug: methotrexate Given IV Drug: methylprednisolone Given IV Drug: prednisone Given PO Drug: vincristine sulfate Given IV
Active Comparator: Group 2 Patients receive vincristine sulfate IV on day 1; cyclophosphamide IV over 15 minutes on day 1; prednisone PO BID or methylprednisolone IV on days 1-7; methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1, 3, and 5; and leucovorin calcium PO BID on days 2 and 4. Patients are randomized to 1 of 2 treatment arms.	Drug: cyclophosphamide Given IV Drug: cytarabine Given IV Drug: doxorubicin hydrochloride Given IV Drug: hydrocortisone sodium succinate Given IT Drug: leucovorin calcium Given PO Drug: methotrexate Given IV Drug: methylprednisolone Given IV Drug: prednisone Given PO Drug: vincristine sulfate Given IV
Experimental: Arm III Patients receive rituximab IV on days -2 (course 1) and 1; vincristine sulfate IV on day 1; prednisone PO or methylprednisolone IV on days 1-5; high-dose methotrexate IV over 4 hours on day 1; leucovorin calcium PO every 6 hours on days 2-4; cyclophosphamide IV over 15 minutes on days 2-4; doxorubicin hydrochloride IV on day 2; and methotrexate IT, hydrocortisone IT, and cytarabine IT on days 2, 4, and 6. Treatment repeats every 21 days for 2 courses.	Biological: rituximab Given IV Drug: cyclophosphamide Given IV Drug: cytarabine Given IV Drug: doxorubicin hydrochloride Given IV Drug: etoposide Given IV Drug: hydrocortisone sodium succinate Given IT Drug: leucovorin calcium Given PO Drug: methotrexate Given IV Drug: methylprednisolone Given IV Drug: prednisone Given PO Drug: vincristine sulfate Given IV
Active Comparator: Arm IV Patients receive vincristine sulfate, prednisone or methylprednisolone, high-dose methotrexate, leucovorin calcium, cyclophosphamide, doxorubicin hydrochloride, and methotrexate, hydrocortisone, and cytarabine IT as in arm III.	Drug: cyclophosphamide Given IV Drug: cytarabine Given IV Drug: doxorubicin hydrochloride Given IV Drug: etoposide Given IV Drug: hydrocortisone sodium succinate Given IT Drug: leucovorin calcium Given PO Drug: methotrexate Given IV Drug: methylprednisolone Given IV Drug: prednisone Given PO Drug: vincristine sulfate Given IV

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Eligibility

Ages Eligible for Study:	up to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically proven B-cell malignancies; Burkitt leukemia or B-cell acute leukemia (B-AL) (Burkitt leukemia = L3-AL), or diffuse large B-cell non-Hodgkin lymphoma (NHL), or aggressive mature B-cell NHL not otherwise specified or specifiable (phase III)
- Stage III with elevated LDH level (B-high) [LDH > twice the institutional upper limit of the adult normal values (> Nx2)], any stage IV, or B-AL (phase III)
Histologically or cytologically proven primary mediastinal large B-cell lymphoma (PMLBL) (phase II)
- No central nervous system (CNS) involvement
No follicular lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, or nodular marginal zone lymphoma
Tumor cell negative for CD20 (absence of result due to technical problems in the presence of other characteristics suggestive of BL/DLBCL, including genetic and phenotypic features, is not an exclusion criteria)

PATIENT CHARACTERISTICS:

Males and females of reproductive potential must agree to use an effective contraceptive method during the treatment, and after the end of treatment: 12 months for women and 5 months for men
Able to comply with scheduled follow-up and with management of toxicity
Signed informed consent from patients and/or their parents or legal guardians
No patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ transplantation, previous malignancy of any type, or known positive human immunodeficiency virus (HIV) serology
Not pregnant or nursing
No severe active viral infection, especially hepatitis B virus (HBV)
- Severe infection (such as sepsis, pneumonia, etc.) should be clinically controlled at the time of randomization
No HBV carrier status or positive serology; a patient is considered as HBV carrier or to have (had) HBV infection by any of the following criteria:
- Unimmunized and hepatitis B surface antigen (HBsAg) and/or anti-HBs antibody and/or anti-hepatitis B core (HBc)-antibody positive
- Immunized and HBsAg and/or anti-HBc antibody positive
- For the Phase III trial, a patient without a known history of HBV could be randomized in the study if the serology results are not available at the time of the randomization; however, if the serology results are positive or not available at day 6 (the first day to receive rituximab, if so randomized), the patient must be withdrawn from the study whatever the allocated treatment arm; for the phase II trial, the hepatitis B serology results must be available before registration
No patients who, for any reason, are not able to comply with the national legislation

PRIOR CONCURRENT THERAPY:

No past or current anti-cancer treatment except corticosteroids for less than one week
No participation in another investigational drug clinical trial
No prior exposure to rituximab

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01595048

Show 58 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Thomas G. Gross, MD, PhD

Nationwide Children's Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Peter C. Adamson, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier:	NCT01595048 History of Changes
Other Study ID Numbers:	CDR0000732604, COG-ANHL1131
Study First Received:	May 8, 2012
Last Updated:	November 20, 2012
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

childhood diffuse large cell lymphoma
stage III childhood large cell lymphoma
stage IV childhood large cell lymphoma

B-cell childhood acute lymphoblastic leukemia
L3 childhood acute lymphoblastic leukemia
untreated childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:

Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Cytarabine
Methotrexate
Rituximab
Doxorubicin
Etoposide

Methylprednisolone Hemisuccinate
Prednisolone
Prednisone
Vincristine
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Methylprednisolone acetate
Prednisolone acetate
Hydrocortisone
Methylprednisolone
Hydrocortisone-17-butyrate
Leucovorin
Levoleucovorin
Prednisolone hemisuccinate

ClinicalTrials.gov processed this record on May 19, 2013