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

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center Genentech
Information provided by:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00712582

Purpose

About 60% of patients with DLBCL can be cured with a chemotherapy program. It is called RCHOP-21. 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 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 patients who have these factors is to change the treatment. You will get different chemotherapy after 4 cycles. This type of treatment is called risk-adapted therapy.

Condition	Intervention	Phase
Non-Hodgkin's Lymphoma	Drug: rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Etoposide, Ifosfamide, Carboplatin	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Vincristine Doxorubicin Doxorubicin hydrochloride Etoposide Carboplatin Myocet Etoposide phosphate Rituximab Vincristine sulfate Ifosfamide

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

To determine the 2-year PFS and 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: conclusion of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Obtain preliminary data on biodistribution, dosimetry and potential clinical usefulness of the proliferation marker [18F] fluorothymidine (FLT) in pts with diffuse large cell lymphoma, using combined (FDG-PET/CT). [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]
To determine the role of CT volumetric analysis compared to standard unidimensional CT in this patient population. [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]

Estimated Enrollment:	90
Study Start Date:	July 2008
Estimated Study Completion Date:	July 2012
Estimated Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental The treatment has three parts. Part 1: Induction Part 2: Repeat Tests Part 3: Consolidation Treatment	Drug: rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Etoposide, Ifosfamide, Carboplatin Induction: RR-CHOP-14 Chemotherapy for Three Cycles All induction treatment visits have a +/- 2 day window (excluding the restaging scans). 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 A: Patients whose disease is FDG-PET negative (any residual lesion seen on companion CT with FDG uptake < blood pool activity in large vessels in the same field of view) 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. Each cycle of ICE lasts 14 days. Consolidation B: 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). Consolidation C: Patients with biopsy proven disease after induction therapy

Arms

Assigned Interventions

1: Experimental

The treatment has three parts. Part 1: Induction Part 2: Repeat Tests Part 3: Consolidation Treatment

Drug: rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Etoposide, Ifosfamide, Carboplatin

Induction: RR-CHOP-14 Chemotherapy for Three Cycles All induction treatment visits have a +/- 2 day window (excluding the restaging scans). 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 A: Patients whose disease is FDG-PET negative (any residual lesion seen on companion CT with FDG uptake < blood pool activity in large vessels in the same field of view) 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. Each cycle of ICE lasts 14 days. Consolidation B: 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). Consolidation C: Patients with biopsy proven disease after induction therapy

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.
- 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) 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.
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 and Hepatitis BE antigen negative and Hepatitis C negative.
All patients of childbearing age must be using an acceptable form of birth control.
Women who are pre-menopausal must have a negative pregnancy test
Age between 18 and 70
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.

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
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.
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00712582

Contacts

Contact: Craig Moskowitz, MD		moskowic@mskcc.org
Contact: Lawrence Schwartz, MD		schwartl@mskcc.org

Locations

United States, New York
Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Craig Moskowitz, MD moskowic@mskcc.org
Contact: Lawrence Schwartz, MD schwartl@mskcc.org
Principal Investigator: Craig Moskowitz, MD

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Genentech

Investigators

Principal Investigator:

Craig Moskowitz, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Craig Moskowitz, MD )
Study ID Numbers:	08-026
Study First Received:	July 8, 2008
Last Updated:	July 20, 2009
ClinicalTrials.gov Identifier:	NCT00712582 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Non-Hodgkin
Lymphoma
Rituximab
Cyclophosphamide
Doxorubicin

Vincristine
ifosfamide
etoposide
carboplatin

Study placed in the following topic categories:

Immunologic Factors
Cyclophosphamide
Etoposide phosphate
Lymphoma, Small Cleaved-cell, Diffuse
Lymphoma, B-Cell
Anti-Bacterial Agents
Lymphoma, Large-cell
Lymphoma
Etoposide
Alkylating Agents
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Vincristine

Antimitotic Agents
Carboplatin
Immunosuppressive Agents
Doxorubicin
Lymphatic Diseases
Ifosfamide
B-cell Lymphomas
Tubulin Modulators
Antineoplastic Agents, Alkylating
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Isophosphamide mustard

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Lymphoma, B-Cell
Therapeutic Uses
Lymphoma
Etoposide
Alkylating Agents
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases

Rituximab
Mitosis Modulators
Vincristine
Antimitotic Agents
Carboplatin
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Lymphatic Diseases
Ifosfamide
Neoplasms
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on September 03, 2009