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

Primary Purpose

Lymphoma

Status

Unknown status

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

pegfilgrastim

rituximab

cyclophosphamide

cytarabine

doxorubicin hydrochloride

etoposide phosphate

ifosfamide

leucovorin calcium

methotrexate

vincristine sulfate

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Nottingham City HospitalRecruiting

Outcomes

Primary Outcome Measures

Complete response rate

Secondary Outcome Measures

Toxicity

Progression-free survival

Full Information

NCT ID

NCT00974792

First Posted

September 9, 2009

Last Updated

August 23, 2013

Sponsor

Cancer Research UK

1. Study Identification

Unique Protocol Identification Number

NCT00974792

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2009

Overall Recruitment Status

Unknown status

Study Start Date

January 2006 (undefined)

Primary Completion Date

May 2011 (Anticipated)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

Cancer Research UK

4. Oversight

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma

Keywords

stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Masking

None (Open Label)

Enrollment

150 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

pegfilgrastim

Intervention Type

Biological

Intervention Name(s)

rituximab

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide

Intervention Type

Drug

Intervention Name(s)

cytarabine

Intervention Type

Drug

Intervention Name(s)

doxorubicin hydrochloride

Intervention Type

Drug

Intervention Name(s)

etoposide phosphate

Intervention Type

Drug

Intervention Name(s)

ifosfamide

Intervention Type

Drug

Intervention Name(s)

leucovorin calcium

Intervention Type

Drug

Intervention Name(s)

methotrexate

Intervention Type

Drug

Intervention Name(s)

vincristine sulfate

Primary Outcome Measure Information:

Title

Complete response rate

Secondary Outcome Measure Information:

Title

Toxicity

Title

Progression-free survival

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

A. McMillan

Organizational Affiliation

Nottingham City Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Nottingham City Hospital

City

Nottingham

State/Province

England

ZIP/Postal Code

NG5 1PB

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

A. McMillan

Phone

44-115-969-1169

12. IPD Sharing Statement

Citations:

PubMed Identifier

32464282

Citation

McMillan AK, Phillips EH, Kirkwood AA, Barrans S, Burton C, Rule S, Patmore R, Pettengell R, Ardeshna KM, Lawrie A, Montoto S, Paneesha S, Clifton-Hadley L, Linch DC. Favourable outcomes for high-risk diffuse large B-cell lymphoma (IPI 3-5) treated with front-line R-CODOX-M/R-IVAC chemotherapy: results of a phase 2 UK NCRI trial. Ann Oncol. 2020 Sep;31(9):1251-1259. doi: 10.1016/j.annonc.2020.05.016. Epub 2020 May 26.

Results Reference

derived

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

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