Therapy for Patients With Untreated Age-Adjusted International Prognostic Index Low-Intermediate Risk, High-Intermediate Risk, or High Risk Diffuse Large B Cell Lymphoma

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00712582
• Collaborator: Genentech, Inc. (Industry), Columbia University (Other)
• Enrollment: 96
• Location: 1
• Arms: 3
• Actual Duration (Months): 152.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

About 60% of patients with DLBCL can be cured with a chemotherapy program. It is called RCHOP-21 (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone). It is given once every 3 weeks, for 18 weeks. Each three weeks is a cycle. Some factors predict that you may not be cured with R-CHOP-21. The most common ones are:

• Stage - how much DLBCL, PMBL, or FL3B you have

• LDH - a blood chemistry marker; and

• Whether you can do your normal daily activities. (performance status) We think that the best way to cure more patients with poor risk factors is to add new treatment to R-CHOP. You will get different chemotherapy after 4 cycles. This type of treatment is called risk-adapted therapy.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma	Drug: Etoposide, carboplatin, ifosfamide; Drug: Rituximab, Ifosfamide, Etoposide, Carboplatin; Drug: Rituximab, Ifosfamide, Etoposide, Carboplatin, Stem Cell Collection, Mitoxantrone, Cyclophosphamide and etoposide, Carmustine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 96 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Risk-Adapted Therapy for Patients With Untreated Age-Adjusted International Prognostic Index Low-Intermediate Risk, High-Intermediate Risk, or High Risk Diffuse Large B Cell Lymphoma
• Actual Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: Mar 12, 2021
• Actual Study Completion Date: Mar 12, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Consolidation A Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is < 80% will receive 3 cycles of standard dose ICE Chemotherapy.	Drug: Etoposide, carboplatin, ifosfamide; Patients in consolidation A will receive three drugs in a regimen called ICE. You will have 3 cycles. Each new cycle begins 2 to 3 weeks after the last one.
Experimental: Consolidation B Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is ≥80% will receive 2 cycles of augmented RICE Chemotherapy (as per MSKCC protocol 03-075).	Drug: Rituximab, Ifosfamide, Etoposide, Carboplatin; It consists of four drugs in a regimen called augmented RICE (augRICE). It is given every 3 weeks for 2 cycles.
Experimental: Consolidation C Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Consolidation C: Patients with biopsy proven disease after induction therapy. Patients whose bone marrow remain positive at interim restaging will have the option of getting an allogeneic[m3] stem cell transplant, in lieu of an ASCT, if they have an acceptable HLA match donor. The allogeneic[m4] stem cell transplant regimen will be decided by the MSK Bone Marrow Transplant Service.	Drug: Rituximab, Ifosfamide, Etoposide, Carboplatin, Stem Cell Collection, Mitoxantrone, Cyclophosphamide and etoposide, Carmustine; It consists of four drugs in a regimen called augRICE. It is given every 3 weeks for 2 cycles. After the rituximab on day 3, you will then be admitted to the hospital for 2 to 3 nights. Part 2: Stem Cell Collection, Part 3: High dose chemoradiotherapy and stem cell transplant. Your doctor may want you to get radiation therapy. If so, it will start 2 weeks before the highdose chemotherapy. This regimen is called CBV-N chemotherapy. It is given by vein in the hospital.

Outcome Measures

Primary Outcome Measures

1. 2-year PFS From the Start of Induction Therapy Conditional [2 years]

   2-year PFS from the start of induction therapy conditional on attaining either a negative FDG-PET or a negative biopsy at the interim evaluation.

Secondary Outcome Measures

1. Overall Survival at 1 Year [1 year]

   Overall survival from the start of induction therapy conditional on attaining either a negative FDG-PET or a negative biopsy at the interim evaluation.

2. Proliferation Marker [18F] Fluorothymidine (FLT) is Significantly Predictive of Progression Free Survival/PFS Via a Log Rank Test. [Through study completion, up to 10 years]

   Obtain preliminary data on potential clinical usefulness of the proliferation marker [18F] fluorothymidine (FLT) in pts with diffuse large cell lymphoma, using combined (FDG-PET/CT). 18F-FLT uptake by visual analysis (stratified as grades 1-3 vs grades 4-5)

3. Proliferation Marker [18F] Fluorothymidine (FLT) Significantly Predictive of Overall Survival/OS Via a Log Rank Test. [Through the completion of study, up to 10 years]

   Obtain preliminary data on potential clinical usefulness of the proliferation marker [18F] fluorothymidine (FLT) in pts with diffuse large cell lymphoma, using combined (FDG-PET/CT). 18F-FLT uptake by visual analysis (stratified as grades 1-3 vs grades 4-5)

4. To Determine the Role of CT Volumetric Analysis Compared to Standard Unidimensional CT in This Patient Population. [conclusion of study]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologic diagnosis of diffuse large B cell lymphoma, PMLBL, or follicular lymphoma grade 3B confirmed by the department of hematopathology at MSKCC: Patients with discordant bone marrow involvement (i.e. involvement by small cleaved cells or small lymphocytic lymphoma) are eligible.

• Tumors express CD20 as determined by immunohistochemistry.

o Ki-67 evaluation of tumor tissue

• Patients must have stage III, or IV disease. Patients with IIX, disease must have at least one other age-adjusted IPI risk factor.

• KPS ≤ 70

• LDH > upper limit of normal

• All patients must have FDG-PET avid (minimum SUV 2.5) measurable disease

• Patients must have normal baseline cardiac function based upon echocardiogram or gated blood pool scan (MUGA) with an ejection fraction ≥ 50%

• Patients must have a serum creatinine of ≤ 1.5 mg/dl; if creatinine >1.5 mg/dl creatinine clearance must be >60 ml/minute.

• Patients must have ANC>1000/mcl and Platelets>50,000/mcl. If patient has cytopenias due to bone marrow involvement, these requirements are not applicable.

• Patients must have a bilirubin level of < 2.0 mg/dl in the absence of a history of Gilbert's disease (or pattern consistent with Gilbert's)

• Patients must be Hepatitis B surface antigen negative, Hepatitis B core antibody negative, and Hepatitis C negative.

• All patients of childbearing and child creating age must be using an acceptable form of birth control from the initiation of treatment on study until 1 year after completion of chemotherapy and/or transplant.

• Women who are pre-menopausal must have a negative pregnancy test

• Age between 18 and 65

• Patients must be HIV negative. This test may be pending in a patient without risk factors, as determined by the patient's physician.

• If patients have a history of malignancy other than cutaneous basal cell or squamous cell carcinoma, they must be disease-free for ≥ 5 years at the time of enrollment.

• Patients or their guardians must be capable of providing informed consent.

• Patients must be suitable to undergo stem cell transplant.

Exclusion Criteria:

• Any lymphoma subtype other than DLBCL, PMLBL, follicular lymphoma grade 3B

• Patients with either parenchymal brain or lepto-meningeal involvement.

• No more than 14 days of prednisone therapy between the diagnostic biopsy of either DLBCL, PMLBL, or follicular lymphoma grade 3B and the initiation of treatment on study.

• Known pregnancy or breast-feeding

• Medical illness unrelated to NHL which in the opinion of the attending physician and principal investigator will preclude administration of chemotherapy safely. This includes patients with uncontrolled infection, chronic renal insufficiency, myocardial infarction within the past 6 months, unstable angina, cardiac arrhythmias other than chronic atrial fibrillation and chronic active or persistent hepatitis, or New York Heart Association Classification III or IV heart disease.

• History of any malignancy for which the disease-free interval is <5 years, excluding curatively treated cutaneous basal cell or squamous cell carcinoma and carcinoma in-situ of the cervix.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• Genentech, Inc.
• Columbia University

Investigators

• Principal Investigator: Andrew Zelenetz, MD, PhD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 6, 2019

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00712582
• Other Study ID Numbers: 08-026
• First Posted: Jul 10, 2008
• Last Update Posted: Jun 21, 2022
• Last Verified: Mar 1, 2021

• Keywords provided by Memorial Sloan Kettering Cancer Center: Non-Hodgkin; Lymphoma; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; ifosfamide; etoposide; carboplatin; stem cell transplant; 08-026
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse; Cyclophosphamide; Ifosfamide; Isophosphamide mustard; Carmustine; Rituximab; Carboplatin; Etoposide; Etoposide phosphate; Mitoxantrone

Study Results

Participant Flow

Arm/Group Title	Consolidation A	Consolidation B	Consolidation C
Arm/Group Description	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is < 80% will receive 3 cycles of standard dose ICE Chemotherapy. Etoposide, carboplatin, ifosfamide: Patients in consolidation A will receive three drugs in a regimen called ICE. You will have 3 cycles. Each new cycle begins 2 to 3 weeks after the last one.	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is ≥80% will receive 2 cycles of augmented RICE Chemotherapy (as per MSKCC protocol 03-075). Rituximab, Ifosfamide, Etoposide, Carboplatin: It consists of four drugs in a regimen called augmented RICE (augRICE). It is given every 3 weeks for 2 cycles.	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Consolidation C: Patients with biopsy proven disease after induction therapy. Patients whose bone marrow remain positive at interim restaging will have the option of getting an allogeneic[m3] stem cell transplant, in lieu of an ASCT, if they have an acceptable HLA match donor. The allogeneic[m4] stem cell transplant regimen will be decided by the MSK Bone Marrow Transplant Service. Rituximab, Ifosfamide, Etoposide, Carboplatin, Stem Cell Collection, Mitoxantrone, Cyclophosphamide and etoposide, Carmustine: It consists of four drugs in a regimen called augRICE. It is given every 3 weeks for 2 cycles. After the rituximab on day 3, you will then be admitted to the hospital for 2 to 3 nights. Part 2: Stem Cell Collection, Part 3: High dose chemoradiotherapy and stem cell transplant. Your doctor may want you to get radiation therapy. If so, it will start 2 weeks before the highdose chemotherapy. This regimen is called CBV-N chemotherapy. It is given by vein in the hospital.
Period Title: Overall Study
STARTED	60	32	4
COMPLETED	60	32	4
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Consolidation A	Consolidation B	Consolidation C	Total
Arm/Group Description	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is < 80% will receive 3 cycles of standard dose ICE Chemotherapy. Etoposide, carboplatin, ifosfamide: Patients in consolidation A will receive three drugs in a regimen called ICE. You will have 3 cycles. Each new cycle begins 2 to 3 weeks after the last one.	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is ≥80% will receive 2 cycles of augmented RICE Chemotherapy (as per MSKCC protocol 03-075). Rituximab, Ifosfamide, Etoposide, Carboplatin: It consists of four drugs in a regimen called augmented RICE (augRICE). It is given every 3 weeks for 2 cycles.	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Consolidation C: Patients with biopsy proven disease after induction therapy. Patients whose bone marrow remain positive at interim restaging will have the option of getting an allogeneic[m3] stem cell transplant, in lieu of an ASCT, if they have an acceptable HLA match donor. The allogeneic[m4] stem cell transplant regimen will be decided by the MSK Bone Marrow Transplant Service. Rituximab, Ifosfamide, Etoposide, Carboplatin, Stem Cell Collection, Mitoxantrone, Cyclophosphamide and etoposide, Carmustine: It consists of four drugs in a regimen called augRICE. It is given every 3 weeks for 2 cycles. After the rituximab on day 3, you will then be admitted to the hospital for 2 to 3 nights. Part 2: Stem Cell Collection, Part 3: High dose chemoradiotherapy and stem cell transplant. Your doctor may want you to get radiation therapy. If so, it will start 2 weeks before the highdose chemotherapy. This regimen is called CBV-N chemotherapy. It is given by vein in the hospital.	Total of all reporting groups
Overall Participants	60	32	4	96
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52	49.5	59	51.45
Sex: Female, Male (Count of Participants)
Female	29 48.3%	19 59.4%	1 25%	49 51%
Male	31 51.7%	13 40.6%	3 75%	47 49%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	60 100%	32 100%	4 100%	96 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	60 100%	32 100%	4 100%	96 100%
Region of Enrollment (Count of Participants)
United States	60 100%	32 100%	4 100%	96 100%

Outcome Measures

1. Primary Outcome

Title	2-year PFS From the Start of Induction Therapy Conditional
Description	2-year PFS from the start of induction therapy conditional on attaining either a negative FDG-PET or a negative biopsy at the interim evaluation.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Consolidation A	Consolidation B	Consolidation C
Arm/Group Description	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is < 80% will receive 3 cycles of standard dose ICE Chemotherapy. Etoposide, carboplatin, ifosfamide: Patients in consolidation A will receive three drugs in a regimen called ICE. You will have 3 cycles. Each new cycle begins 2 to 3 weeks after the last one.	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is ≥80% will receive 2 cycles of augmented RICE Chemotherapy (as per MSKCC protocol 03-075). Rituximab, Ifosfamide, Etoposide, Carboplatin: It consists of four drugs in a regimen called augmented RICE (augRICE). It is given every 3 weeks for 2 cycles.	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Consolidation C: Patients with biopsy proven disease after induction therapy. Patients whose bone marrow remain positive at interim restaging will have the option of getting an allogeneic[m3] stem cell transplant, in lieu of an ASCT, if they have an acceptable HLA match donor. The allogeneic[m4] stem cell transplant regimen will be decided by the MSK Bone Marrow Transplant Service. Rituximab, Ifosfamide, Etoposide, Carboplatin, Stem Cell Collection, Mitoxantrone, Cyclophosphamide and etoposide, Carmustine: It consists of four drugs in a regimen called augRICE. It is given every 3 weeks for 2 cycles. After the rituximab on day 3, you will then be admitted to the hospital for 2 to 3 nights. Part 2: Stem Cell Collection, Part 3: High dose chemoradiotherapy and stem cell transplant. Your doctor may want you to get radiation therapy. If so, it will start 2 weeks before the highdose chemotherapy. This regimen is called CBV-N chemotherapy. It is given by vein in the hospital.
Measure Participants	60	32	4
Number (95% Confidence Interval) [percentage of patients]	86.6	90.6	0.4

2. Secondary Outcome

Title	Overall Survival at 1 Year
Description	Overall survival from the start of induction therapy conditional on attaining either a negative FDG-PET or a negative biopsy at the interim evaluation.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Consolidation A	Consolidation B	Consolidation C
Arm/Group Description	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is < 80% will receive 3 cycles of standard dose ICE Chemotherapy. Etoposide, carboplatin, ifosfamide: Patients in consolidation A will receive three drugs in a regimen called ICE. You will have 3 cycles. Each new cycle begins 2 to 3 weeks after the last one.	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is ≥80% will receive 2 cycles of augmented RICE Chemotherapy (as per MSKCC protocol 03-075). Rituximab, Ifosfamide, Etoposide, Carboplatin: It consists of four drugs in a regimen called augmented RICE (augRICE). It is given every 3 weeks for 2 cycles.	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Consolidation C: Patients with biopsy proven disease after induction therapy. Patients whose bone marrow remain positive at interim restaging will have the option of getting an allogeneic[m3] stem cell transplant, in lieu of an ASCT, if they have an acceptable HLA match donor. The allogeneic[m4] stem cell transplant regimen will be decided by the MSK Bone Marrow Transplant Service. Rituximab, Ifosfamide, Etoposide, Carboplatin, Stem Cell Collection, Mitoxantrone, Cyclophosphamide and etoposide, Carmustine: It consists of four drugs in a regimen called augRICE. It is given every 3 weeks for 2 cycles. After the rituximab on day 3, you will then be admitted to the hospital for 2 to 3 nights. Part 2: Stem Cell Collection, Part 3: High dose chemoradiotherapy and stem cell transplant. Your doctor may want you to get radiation therapy. If so, it will start 2 weeks before the highdose chemotherapy. This regimen is called CBV-N chemotherapy. It is given by vein in the hospital.
Measure Participants	60	32	4
Number (95% Confidence Interval) [Percent of patients]	98.3	96.9	50.0

3. Secondary Outcome

Title	Proliferation Marker [18F] Fluorothymidine (FLT) is Significantly Predictive of Progression Free Survival/PFS Via a Log Rank Test.
Description	Obtain preliminary data on potential clinical usefulness of the proliferation marker [18F] fluorothymidine (FLT) in pts with diffuse large cell lymphoma, using combined (FDG-PET/CT). 18F-FLT uptake by visual analysis (stratified as grades 1-3 vs grades 4-5)
Time Frame	Through study completion, up to 10 years

Outcome Measure Data

Analysis Population Description

N/A - data were not collected

Arm/Group Title	Consolidation A
Arm/Group Description	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is < 80% will receive 3 cycles of standard dose ICE Chemotherapy. Etoposide, carboplatin, ifosfamide: Patients in consolidation A will receive three drugs in a regimen called ICE. You will have 3 cycles. Each new cycle begins 2 to 3 weeks after the last one.
Measure Participants	0

4. Secondary Outcome

Title	Proliferation Marker [18F] Fluorothymidine (FLT) Significantly Predictive of Overall Survival/OS Via a Log Rank Test.
Description	Obtain preliminary data on potential clinical usefulness of the proliferation marker [18F] fluorothymidine (FLT) in pts with diffuse large cell lymphoma, using combined (FDG-PET/CT). 18F-FLT uptake by visual analysis (stratified as grades 1-3 vs grades 4-5)
Time Frame	Through the completion of study, up to 10 years

Outcome Measure Data

Analysis Population Description

N/A - data were not collected

Arm/Group Title	Consolidation A
Arm/Group Description	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is < 80% will receive 3 cycles of standard dose ICE Chemotherapy. Etoposide, carboplatin, ifosfamide: Patients in consolidation A will receive three drugs in a regimen called ICE. You will have 3 cycles. Each new cycle begins 2 to 3 weeks after the last one.
Measure Participants	0

5. Secondary Outcome

Title	To Determine the Role of CT Volumetric Analysis Compared to Standard Unidimensional CT in This Patient Population.
Time Frame	conclusion of study

Outcome Measure Data

Analysis Population Description

N/A - Data were not collected

Arm/Group Title	Consolidation A	Consolidation B	Consolidation C
Arm/Group Description	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is < 80% will receive 3 cycles of standard dose ICE Chemotherapy. Etoposide, carboplatin, ifosfamide: Patients in consolidation A will receive three drugs in a regimen called ICE. You will have 3 cycles. Each new cycle begins 2 to 3 weeks after the last one.	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is ≥80% will receive 2 cycles of augmented RICE Chemotherapy (as per MSKCC protocol 03-075). Rituximab, Ifosfamide, Etoposide, Carboplatin: It consists of four drugs in a regimen called augmented RICE (augRICE). It is given every 3 weeks for 2 cycles.	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Consolidation C: Patients with biopsy proven disease after induction therapy. Patients whose bone marrow remain positive at interim restaging will have the option of getting an allogeneic[m3] stem cell transplant, in lieu of an ASCT, if they have an acceptable HLA match donor. The allogeneic[m4] stem cell transplant regimen will be decided by the MSK Bone Marrow Transplant Service. Rituximab, Ifosfamide, Etoposide, Carboplatin, Stem Cell Collection, Mitoxantrone, Cyclophosphamide and etoposide, Carmustine: It consists of four drugs in a regimen called augRICE. It is given every 3 weeks for 2 cycles. After the rituximab on day 3, you will then be admitted to the hospital for 2 to 3 nights. Part 2: Stem Cell Collection, Part 3: High dose chemoradiotherapy and stem cell transplant. Your doctor may want you to get radiation therapy. If so, it will start 2 weeks before the highdose chemotherapy. This regimen is called CBV-N chemotherapy. It is given by vein in the hospital.
Measure Participants	0	0	0

Adverse Events

Time Frame	Up to 2 years
Arm/Group Title	Consolidation A		Consolidation B		Consolidation C
Arm/Group Description	Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is < 80% will receive 3 cycles of standard dose ICE Chemotherapy. Etoposide, carboplatin, ifosfamide: Patients in consolidation A will receive three drugs in a regimen called ICE. You will have 3 cycles. Each new cycle begins 2 to 3 weeks after the last one.		Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is ≥80% will receive 2 cycles of augmented RICE Chemotherapy (as per MSKCC protocol 03-075). Rituximab, Ifosfamide, Etoposide, Carboplatin: It consists of four drugs in a regimen called augmented RICE (augRICE). It is given every 3 weeks for 2 cycles.		Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow. Consolidation C: Patients with biopsy proven disease after induction therapy. Patients whose bone marrow remain positive at interim restaging will have the option of getting an allogeneic[m3] stem cell transplant, in lieu of an ASCT, if they have an acceptable HLA match donor. The allogeneic[m4] stem cell transplant regimen will be decided by the MSK Bone Marrow Transplant Service. Rituximab, Ifosfamide, Etoposide, Carboplatin, Stem Cell Collection, Mitoxantrone, Cyclophosphamide and etoposide, Carmustine: It consists of four drugs in a regimen called augRICE. It is given every 3 weeks for 2 cycles. After the rituximab on day 3, you will then be admitted to the hospital for 2 to 3 nights. Part 2: Stem Cell Collection, Part 3: High dose chemoradiotherapy and stem cell transplant. Your doctor may want you to get radiation therapy. If so, it will start 2 weeks before the highdose chemotherapy. This regimen is called CBV-N chemotherapy. It is given by vein in the hospital.
All Cause Mortality
	Consolidation A		Consolidation B		Consolidation C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/60 (8.3%)		1/32 (3.1%)		2/4 (50%)
Serious Adverse Events
	Consolidation A		Consolidation B		Consolidation C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/60 (25%)		12/32 (37.5%)		2/4 (50%)
Blood and lymphatic system disorders
Blood/Bone Marrow, other	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
Febrile neutropenia	6/60 (10%)		8/32 (25%)		0/4 (0%)
Hemoglobin	3/60 (5%)		1/32 (3.1%)		1/4 (25%)
Cardiac disorders
Atrial fibrillation	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
Gastrointestinal disorders
Colitis	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
Constipation	2/60 (3.3%)		3/32 (9.4%)		1/4 (25%)
Diarrhea	2/60 (3.3%)		1/32 (3.1%)		0/4 (0%)
Enteritis	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
Nausea	0/60 (0%)		2/32 (6.3%)		1/4 (25%)
Pain - Anus	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
Pain - Rectum	1/60 (1.7%)		0/32 (0%)		0/4 (0%)
Vomiting	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
General disorders
Fatigue	1/60 (1.7%)		1/32 (3.1%)		0/4 (0%)
Fever (in the absence of neutropenia)	2/60 (3.3%)		1/32 (3.1%)		0/4 (0%)
Pain - Chest/thorax NOS	0/60 (0%)		0/32 (0%)		2/4 (50%)
Immune system disorders
Allerg react/hypersens (incl drug fever)	1/60 (1.7%)		0/32 (0%)		0/4 (0%)
Infections and infestations
Pneumonia (lung)	1/60 (1.7%)		0/32 (0%)		0/4 (0%)
Investigations
Creatinine	1/60 (1.7%)		0/32 (0%)		0/4 (0%)
Leukocytes	3/60 (5%)		0/32 (0%)		0/4 (0%)
Neutrophils/granulocytes	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
Platelets	3/60 (5%)		1/32 (3.1%)		0/4 (0%)
Metabolism and nutrition disorders
Hyperglycemia	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
Potassium, low (hypokalemia)	1/60 (1.7%)		0/32 (0%)		0/4 (0%)
Sodium, low (hyponatremia)	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Pain - Back	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
Pain - Neck	1/60 (1.7%)		0/32 (0%)		0/4 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary malig-poss related to ca txt	1/60 (1.7%)		0/32 (0%)		0/4 (0%)
Nervous system disorders
Encephalopathy	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
Syncope (fainting)	1/60 (1.7%)		0/32 (0%)		0/4 (0%)
Psychiatric disorders
Confusion	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
Renal and urinary disorders
Renal/Genitourinary-Other Specify	1/60 (1.7%)		0/32 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
Dyspnea	0/60 (0%)		0/32 (0%)		1/4 (25%)
Hypoxia	0/60 (0%)		1/32 (3.1%)		0/4 (0%)
Vascular disorders
Phlebitis (incl superficial thrombosis)	1/60 (1.7%)		1/32 (3.1%)		0/4 (0%)
Thrombosis/thrombus/embolism	1/60 (1.7%)		1/32 (3.1%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Consolidation A		Consolidation B		Consolidation C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/32 (0%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.