Combination Chemotherapy and Rituximab in Treating Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00974792
First received: September 9, 2009
Last updated: August 23, 2013
Last verified: September 2009
  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 antibodies, such as rituximab, can block cancer cell 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 cell-killing substances to them. Giving more than one drug (combination chemotherapy) together with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with diffuse large B-cell non-Hodgkin lymphoma.


Condition Intervention Phase
Lymphoma
Biological: pegfilgrastim
Biological: rituximab
Drug: cyclophosphamide
Drug: cytarabine
Drug: doxorubicin hydrochloride
Drug: etoposide phosphate
Drug: ifosfamide
Drug: leucovorin calcium
Drug: methotrexate
Drug: vincristine sulfate
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Single Arm Study of the Use of CODOX-M/IVAC With Rituximab (R-CODOX-M/IVAC) in the Treatment of Patients With Diffuse Large B-Cell Lymphoma (International Prognostic Index High or High-Intermediate Risk)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Complete response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Designated as safety issue: Yes ]
  • Progression-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: January 2006
Estimated Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the complete response rate in patients with high- or high/intermediate-risk diffuse large B-cell lymphoma treated with CODOX-M/IVAC comprising cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, methotrexate, ifosfamide, etoposide phosphate, and cytarabine with rituximab.

Secondary

  • Determine the toxicity of this regimen in these patients.
  • Determine the progression-free survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV on days 1 and 11 and CODOX-M comprising doxorubicin hydrochloride IV on day 1, cyclophosphamide IV on days 1-5, vincristine sulfate IV on days 1 and 8, methotrexate IV over 12 hours on day 10, and leucovorin calcium IV or orally every 3-6 hours beginning 24-36 hours after methotrexate. Patients also receive CNS prophylaxis comprising cytarabine intrathecally (IT) on days 1 and 3 and methotrexate IT on day 15. Patients with high-risk disease receive an additional dose of cytarabine IT on day 5 and methotrexate IT on day 17. Patients also receive pegfilgrastim subcutaneously (SC) on day 11. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of CODOX-M course 1, patients receive rituximab IV on day 1** and IVAC comprising etoposide phosphate IV over 1 hour and ifosfamide IV over 1 hour on days 1-5, cytarabine IV over 3 hours (every 12 hours) on days 1 and 2, and methotrexate IT on day 5. Patients with high-risk disease receive cytarabine IT on days 7 and 9. Patients also receive pegfilgrastim SC on day 7. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

NOTE: **Patients with high-risk disease also receive rituximab IV on days 21 and 42 after day 1 of course 4 (IVAC).

Treatment with R-CODOX-M and R-IVAC repeats every 28 days alternatively for 2 courses each in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up periodically.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed diffuse large B-cell non-Hodgkin lymphoma

    • International Prognostic Index (IPI) score high-intermediate (score = 3) OR high (score = 4 or 5), defined as:

      • Stage III or IV disease
      • Raised lactic dehydrogenase and poor performance status (WHO performance status 2-4)
    • All morphological variants included
    • B-cell nature of the proliferation must be verified by a positive anti-CD20 antibody (i.e., CD20-positive disease)
  • No T-cell lymphoma
  • No history of treated or non-treated indolent lymphoma

    • Patients newly diagnosed who have large B-cell lymphoma with some small cell infiltration in the bone marrow or lymph node may be allowed

PATIENT CHARACTERISTICS:

  • See Disease Characteristics
  • Life expectancy > 3 months
  • ANC > 1,500/mm^3*
  • Platelet count > 100,000/mm^3*
  • Serum creatinine < 150 μmol/L*
  • Serum bilirubin < 35 μmol/L*
  • AST and/or ALT < 2.5 times upper limit of normal* NOTE: *Unless attributed to bone marrow infiltration by lymphoma.
  • Fertile patients must use effective contraception
  • Normal MUGA or echocardiogram without areas of abnormal contractility
  • LVEF ≥ 50% and only tested if patient meets 1 of the following criteria:

    • History of diabetes
    • Prior cardiac disease, hypertension, or abnormal resting ECG
  • No history of heart failure or uncontrolled angina pectoris
  • No cardiac contraindication to doxorubicin hydrochloride (e.g., abnormal contractility on echocardiography or MUGA)
  • No neurological contraindication to vincristine sulfate (e.g., pre-existing diabetic neuropathy)
  • No concurrent uncontrolled medical condition
  • No other serious active disease
  • No general status that, according to the investigator, does not allow the administration of 2 courses of CODOX-M/IVAC
  • No active malignant disease within the past 10 years except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix
  • No positive serology for HIV or hepatitis B or C
  • No medical or psychiatric conditions that compromise the patient's ability to give informed consent

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior chemotherapy, radiotherapy, or other investigational drug for diffuse large B-cell non-Hodgkin lymphoma
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00974792

Locations
United Kingdom
Nottingham City Hospital Recruiting
Nottingham, England, United Kingdom, NG5 1PB
Contact: A. McMillan    44-115-969-1169      
Sponsors and Collaborators
Cancer Research UK
Investigators
Principal Investigator: A. McMillan Nottingham City Hospital
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00974792     History of Changes
Other Study ID Numbers: CDR0000644893, CRUK-UCL-R-CODOX-M/IVAC, EUDRACT-2005-003479-19, EU-20956
Study First Received: September 9, 2009
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Doxorubicin
Etoposide
Etoposide phosphate
Levoleucovorin
Liposomal doxorubicin
Methotrexate
Rituximab
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Antibiotics, Antineoplastic
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on October 30, 2014