Clinical Trials Logo

Clinical Trial Summary

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.


Clinical Trial Description

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 ;


Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms

  • Burkitt Lymphoma
  • Childhood Burkitt Lymphoma
  • Childhood Diffuse Large Cell Lymphoma
  • Childhood Immunoblastic Large Cell Lymphoma
  • Leukemia
  • Leukemia, B-Cell
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, Non-Hodgkin
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Stage I Childhood Large Cell Lymphoma
  • Stage I Childhood Small Noncleaved Cell Lymphoma
  • Stage II Childhood Large Cell Lymphoma
  • Stage II Childhood Small Noncleaved Cell Lymphoma
  • Stage III Childhood Large Cell Lymphoma
  • Stage III Childhood Small Noncleaved Cell Lymphoma
  • Stage IV Childhood Large Cell Lymphoma
  • Stage IV Childhood Small Noncleaved Cell Lymphoma
  • Untreated Childhood Acute Lymphoblastic Leukemia

NCT number NCT00057811
Study type Interventional
Source Children's Oncology Group
Contact
Status Completed
Phase Phase 2
Start date June 2004
Completion date July 2014

See also
  Status Clinical Trial Phase
Completed NCT01427881 - Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies Phase 2
Completed NCT01093586 - Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies Phase 2
Completed NCT00078858 - Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant Phase 1/Phase 2
Completed NCT01748721 - MORAb-004 in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma Phase 1
Terminated NCT00101205 - Oxaliplatin, Ifosfamide and Etoposide in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma Phase 1
Completed NCT00105001 - Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus in Preventing Acute Graft-Versus-Host Disease in Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer Phase 2
Terminated NCT00058461 - Combination Chemotherapy and Rituximab in Treating Young Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Acute Lymphoblastic Leukemia Phase 2
Completed NCT00040846 - Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies Phase 2
Completed NCT00112593 - Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer N/A
Completed NCT00458731 - Bevacizumab and Cediranib Maleate in Treating Patients With Metastatic or Unresectable Solid Tumor, Lymphoma, Intracranial Glioblastoma, Gliosarcoma or Anaplastic Astrocytoma Phase 1
Completed NCT00006251 - Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer Phase 1/Phase 2
Completed NCT01959477 - Dose Monitoring of Busulfan and Combination Chemotherapy in Hodgkin or Non-Hodgkin Lymphoma Undergoing Stem Cell Transplant Phase 0
Active, not recruiting NCT00118352 - Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer Phase 2
Completed NCT00101270 - Oxaliplatin and Irinotecan in Treating Young Patients With Refractory Solid Tumors or Lymphomas Phase 1
Completed NCT00536601 - High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors N/A
Active, not recruiting NCT01595048 - Combination Chemotherapy With or Without Rituximab in Treating Younger Patients With Stage III-IV Non-Hodgkin Lymphoma or B-Cell Acute Leukemia Phase 2/Phase 3
Terminated NCT00933985 - Obatoclax Mesylate, Vincristine Sulfate, Doxorubicin Hydrochloride, and Dexrazoxane Hydrochloride in Treating Young Patients With Relapsed or Refractory Solid Tumors, Lymphoma, or Leukemia Phase 1
Completed NCT01231919 - MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia Phase 1
Completed NCT00856388 - Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders N/A
Completed NCT01529827 - Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies Phase 2