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

Back to results

Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Filgrastim

Pegfilgrastim

Rituximab

Cyclophosphamide

Pegylated liposomal doxorubicin hydrochloride

Prednisone

Vincristine Sulfate

About this trial

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

Eligibility Criteria

61 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed diffuse large B-cell lymphoma Stage II, III, or IV disease Previously untreated disease Measurable or evaluable disease No primary central nervous system (CNS) lymphoma or follicular B-cell lymphoma PATIENT CHARACTERISTICS: Age 61 and over Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count > 1,000/mm^3* Platelet count > 100,000/mm^3* NOTE: * Unless due to lymphoma-related hypersplenism or bone marrow infiltration Hepatic Bilirubin < 2 mg/dL Hepatitis B surface antigen negative Hepatitis B core antibody negative Hepatitis C Virus antibody negative Renal Creatinine < 2 mg/dL Cardiovascular left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or ple gated acquisition (MUGA) scan No uncontrolled hypertension or cardiac symptoms Cardiologist consultation required for patients with stage A cardiac failure or any of the following known heart diseases: Diastolic dysfunction Prior coronary artery bypass graft Prior percutaneous transluminal coronary angioplasty Prior stent insertion Prior radiotherapy to the chest No myocardial infarction within the past 6 months No New York Heart Association class II-IV heart failure No uncontrolled angina No severe uncontrolled ventricular arrhythmias No clinically significant pericardial disease No acute ischemic or active conduction system abnormality by electrocardiogram (EKG) Other Not pregnant or nursing Fertile patients must use effective contraception No psychiatric illness that would preclude study compliance or giving informed consent No other major life-threatening illness that would preclude study treatment PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy See Cardiovascular Surgery See Cardiovascular

Sites / Locations

Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
CCOP - Grand Rapids
CCOP - Kalamazoo
Cancer Research for the Ozarks
Hematology Oncology Associates of Central New York, PC - Northeast Center
CCOP - Upstate Carolina
University of Texas M.D. Anderson CCOP Research Base

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rituximab - Combination Chemotherapy

Arm Description

Rituximab 375 mg/m^2 intravenous (IV), Cyclophosphamide IV over 1-1½ hours, Pegylated doxorubicin HCl liposome 40 mg/m^2 IV over 1 hour, Vincristine 2 mg IV, day 1, & oral Prednisone 40 mg/m^2 days 1 - 5; Filgrastim (G-CSF) 5 mcg/kg subcutaneously (SC) once daily beginning day 6 continuing until blood counts recover OR Pegfilgrastim 6 mg SC once on day 6 (24 hours after chemotherapy). Treatment repeats every 21 days for up to 8 courses.

Outcomes

Primary Outcome Measures

Disease Response (Complete, Complete Unconfirmed, and Partial Responses) After 4 Courses

Response was defined as participants with a complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on International Workshop Criteria (IWG) for Tumor Response Criteria assessed with CT & FDG-PET scans at 4 cycles (12 weeks). CR defined as disappearance of all target and non-target lesions in liver & spleen, & all lymph node masses regressed to normal size. PR defined as ≥50% reduction in sum of product of diameters (SPD) for measured lymph nodes, splenic & liver lesions separately compared to baseline SPD. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate bone marrow.

Number of Participants Experienced Grade 3 or Higher Cardiac Toxicity After Treatment: Cardiac Toxicity as Measured by Left Ventricular Ejection Fraction (LVEF) on Echocardiogram (ECHO) After 8 Courses

Ejection fraction ( EF) refers to the amount, or percentage, of blood that is pumped (or ejected) out of the ventricles with each contraction. Cardiology evaluation performed before second dose of pegylated liposomal doxorubicin or before entry onto trial, re-evaluation by cardiologist obtained in asymptomatic patients after chemotherapy cycle 4 and again after completion of therapy, and more often if symptomatic. Severe cardiac toxicity considered to be both Grade 3 and 4, and are graded according to NCI common toxicity criteria, CTCAE version 3.0.

Secondary Outcome Measures

Survival Rate

The percentage of participants still alive after treatment. Survival information obtained 1 month after completion of treatment, then every 3 months for 1 year, every 4 months for one year and every 6 months thereafter.

Disease-free Survival

The percentage of participants with no disease progression for period of time after treatment. Survival assessed every 3 months for 1 year, every 4 months for 2 years, every 6 months for 3 years, and then yearly thereafter up to 5 years.

Full Information

NCT ID

NCT00101010

First Posted

January 7, 2005

Last Updated

September 22, 2020

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI), Ortho Biotech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00101010

Brief Title

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

Official Title

A Phase II Study Of Rituximab-CHOP With Pegylated Liposomal Doxorubicin In Patients Older Than 60 Years Of Age With Untreated Aggressive B-Cell Non-Hodgkin's Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Completed

Study Start Date

September 2005 (undefined)

Primary Completion Date

September 2014 (Actual)

Study Completion Date

September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI), Ortho Biotech, Inc.

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer 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. 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. Giving rituximab together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating older patients with diffuse large B-cell lymphoma.

Detailed Description

OBJECTIVES: Primary Determine the clinical response rate in older patients with previously untreated aggressive diffuse large B-cell stage II-IV lymphoma treated with rituximab, cyclophosphamide, pegylated doxorubicin hydrochloride liposome (HCl), vincristine, and prednisone. Determine the cardiotoxicity and myelosuppression of this regimen in these patients. Secondary Determine disease-free survival and overall survival of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive rituximab intravenous (IV), cyclophosphamide IV over 1-1½ hours, pegylated doxorubicin HCl liposome IV over 1 hour, and vincristine IV on day 1, and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 6 and continuing until blood counts recover OR pegfilgrastim SC once on day 6 (24 hours after the completion of chemotherapy). Treatment repeats every 21 days for up to 8 courses in the absence of unacceptable toxicity, disease progression, active hepatitis B virus infection, or hepatitis. Patients with no response OR who achieve less than a partial response after 4 courses are removed from the study. Patients are followed at 1 month, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter. PROJECTED ACCRUAL: A maximum of 80 patients will be accrued for this study within 27 months.

6. Conditions and Keywords

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

Lymphoma

Keywords

contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

80 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Rituximab - Combination Chemotherapy

Arm Type

Experimental

Arm Description

Rituximab 375 mg/m^2 intravenous (IV), Cyclophosphamide IV over 1-1½ hours, Pegylated doxorubicin HCl liposome 40 mg/m^2 IV over 1 hour, Vincristine 2 mg IV, day 1, & oral Prednisone 40 mg/m^2 days 1 - 5; Filgrastim (G-CSF) 5 mcg/kg subcutaneously (SC) once daily beginning day 6 continuing until blood counts recover OR Pegfilgrastim 6 mg SC once on day 6 (24 hours after chemotherapy). Treatment repeats every 21 days for up to 8 courses.

Intervention Type

Biological

Intervention Name(s)

Filgrastim

Other Intervention Name(s)

G-CSF, Neupogen

Intervention Description

5 mcg/kg, SC daily, start 24 hours after chemotherapy

Intervention Type

Biological

Intervention Name(s)

Pegfilgrastim

Other Intervention Name(s)

Neulasta, PEG-G-CSF

Intervention Description

6 mg SC one time (24 hours after chemotherapy)

Intervention Type

Biological

Intervention Name(s)

Rituximab

Other Intervention Name(s)

Rituxan

Intervention Description

375 mg/m^2 intravenous piggy back (IVPB) on day 1, administered 1st

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan, Neosar

Intervention Description

750 mg/m^2 IVPB on day 1

Intervention Type

Drug

Intervention Name(s)

Pegylated liposomal doxorubicin hydrochloride

Other Intervention Name(s)

Caelyx, Doxil, liposomal doxorubicin, doxorubicin hydrochloride, liposomal doxorubicin hydrochloride

Intervention Description

40 mg/m^2 IV (maximum dose 90 mg) infusion over 1 hour on day 1

Intervention Type

Drug

Intervention Name(s)

Prednisone

Intervention Description

40 mg/m^2 oral days 1 - 5.

Intervention Type

Drug

Intervention Name(s)

Vincristine Sulfate

Intervention Description

2 mg IV, day 1

Primary Outcome Measure Information:

Title

Disease Response (Complete, Complete Unconfirmed, and Partial Responses) After 4 Courses

Description

Response was defined as participants with a complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on International Workshop Criteria (IWG) for Tumor Response Criteria assessed with CT & FDG-PET scans at 4 cycles (12 weeks). CR defined as disappearance of all target and non-target lesions in liver & spleen, & all lymph node masses regressed to normal size. PR defined as ≥50% reduction in sum of product of diameters (SPD) for measured lymph nodes, splenic & liver lesions separately compared to baseline SPD. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate bone marrow.

Time Frame

Evaluation after 12 weeks (4 cycles of 21 days)

Title

Number of Participants Experienced Grade 3 or Higher Cardiac Toxicity After Treatment: Cardiac Toxicity as Measured by Left Ventricular Ejection Fraction (LVEF) on Echocardiogram (ECHO) After 8 Courses

Description

Ejection fraction ( EF) refers to the amount, or percentage, of blood that is pumped (or ejected) out of the ventricles with each contraction. Cardiology evaluation performed before second dose of pegylated liposomal doxorubicin or before entry onto trial, re-evaluation by cardiologist obtained in asymptomatic patients after chemotherapy cycle 4 and again after completion of therapy, and more often if symptomatic. Severe cardiac toxicity considered to be both Grade 3 and 4, and are graded according to NCI common toxicity criteria, CTCAE version 3.0.

Time Frame

Up to 24 weeks (8 cycles of 21 days)

Secondary Outcome Measure Information:

Title

Survival Rate

Description

The percentage of participants still alive after treatment. Survival information obtained 1 month after completion of treatment, then every 3 months for 1 year, every 4 months for one year and every 6 months thereafter.

Time Frame

Up to 5 years

Title

Disease-free Survival

Description

The percentage of participants with no disease progression for period of time after treatment. Survival assessed every 3 months for 1 year, every 4 months for 2 years, every 6 months for 3 years, and then yearly thereafter up to 5 years.

Time Frame

Up to 5 years or until disease progression

10. Eligibility

Sex

All

Minimum Age & Unit of Time

61 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

DISEASE CHARACTERISTICS: Histologically confirmed diffuse large B-cell lymphoma Stage II, III, or IV disease Previously untreated disease Measurable or evaluable disease No primary central nervous system (CNS) lymphoma or follicular B-cell lymphoma PATIENT CHARACTERISTICS: Age 61 and over Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count > 1,000/mm^3* Platelet count > 100,000/mm^3* NOTE: * Unless due to lymphoma-related hypersplenism or bone marrow infiltration Hepatic Bilirubin < 2 mg/dL Hepatitis B surface antigen negative Hepatitis B core antibody negative Hepatitis C Virus antibody negative Renal Creatinine < 2 mg/dL Cardiovascular left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or ple gated acquisition (MUGA) scan No uncontrolled hypertension or cardiac symptoms Cardiologist consultation required for patients with stage A cardiac failure or any of the following known heart diseases: Diastolic dysfunction Prior coronary artery bypass graft Prior percutaneous transluminal coronary angioplasty Prior stent insertion Prior radiotherapy to the chest No myocardial infarction within the past 6 months No New York Heart Association class II-IV heart failure No uncontrolled angina No severe uncontrolled ventricular arrhythmias No clinically significant pericardial disease No acute ischemic or active conduction system abnormality by electrocardiogram (EKG) Other Not pregnant or nursing Fertile patients must use effective contraception No psychiatric illness that would preclude study compliance or giving informed consent No other major life-threatening illness that would preclude study treatment PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy See Cardiovascular Surgery See Cardiovascular

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Maria A. Rodriguez, MD

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Study Chair

Facility Information:

Facility Name

Hembree Mercy Cancer Center at St. Edward Mercy Medical Center

City

Fort Smith

State/Province

Arkansas

ZIP/Postal Code

72913

Country

United States

Facility Name

CCOP - Grand Rapids

City

Grand Rapids

State/Province

Michigan

ZIP/Postal Code

49503

Country

United States

Facility Name

CCOP - Kalamazoo

City

Kalamazoo

State/Province

Michigan

ZIP/Postal Code

49007-3731

Country

United States

Facility Name

Cancer Research for the Ozarks

City

Springfield

State/Province

Missouri

ZIP/Postal Code

65804

Country

United States

Facility Name

Hematology Oncology Associates of Central New York, PC - Northeast Center

City

East Syracuse

State/Province

New York

ZIP/Postal Code

13057-4510

Country

United States

Facility Name

CCOP - Upstate Carolina

City

Spartanburg

State/Province

South Carolina

ZIP/Postal Code

29303

Country

United States

Facility Name

University of Texas M.D. Anderson CCOP Research Base

City

Houston

State/Province

Texas

ZIP/Postal Code

77030-4009

Country

United States

Lymphoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial