Non-Hodgkin's Lymphoma
Conditions
Keywords
Non-Hodgkin, Lymphoma, Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, ifosfamide, etoposide, carboplatin, stem cell transplant, 08-026
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.
Interventions
DRUGEtoposide, 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.
DRUGRituximab, Ifosfamide, Etoposide, Carboplatin
It consists of four drugs in a regimen called augmented RICE (augRICE). It is given every 3 weeks for 2 cycles.
DRUGRituximab, 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.
Sponsors
Genentech, Inc.
Columbia University
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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) |
| 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) |
| To Determine the Role of CT Volumetric Analysis Compared to Standard Unidimensional CT in This Patient Population. | conclusion of study | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 60 |
| 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).
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. | 32 |
| 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.
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. | 4 |
| Total | 96 |
Baseline characteristics
| Characteristic | Consolidation A | Total | Consolidation C | Consolidation B |
|---|---|---|---|---|
| Age, Continuous | 52 years | 51.45 years | 59 years | 49.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 60 Participants | 96 Participants | 4 Participants | 32 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 60 Participants | 96 Participants | 4 Participants | 32 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 60 Participants | 96 Participants | 4 Participants | 32 Participants |
| Sex: Female, Male Female | 29 Participants | 49 Participants | 1 Participants | 19 Participants |
| Sex: Female, Male Male | 31 Participants | 47 Participants | 3 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 60 | 1 / 32 | 2 / 4 |
| other Total, other adverse events | 0 / 60 | 0 / 32 | 0 / 4 |
| serious Total, serious adverse events | 15 / 60 | 12 / 32 | 2 / 4 |
Outcome results
Primary
2-year PFS From the Start of Induction Therapy Conditional
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Consolidation A | 2-year PFS From the Start of Induction Therapy Conditional | 86.6 percentage of patients |
| Consolidation B | 2-year PFS From the Start of Induction Therapy Conditional | 90.6 percentage of patients |
| Consolidation C | 2-year PFS From the Start of Induction Therapy Conditional | 0.4 percentage of patients |
Secondary
Overall Survival at 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.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Consolidation A | Overall Survival at 1 Year | 98.3 Percent of patients |
| Consolidation B | Overall Survival at 1 Year | 96.9 Percent of patients |
| Consolidation C | Overall Survival at 1 Year | 50.0 Percent of patients |
Secondary
Proliferation Marker [18F] Fluorothymidine (FLT) is Significantly Predictive of Progression Free Survival/PFS Via a Log Rank Test.
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
Population: N/A - data were not collected
Secondary
Proliferation Marker [18F] Fluorothymidine (FLT) Significantly Predictive of Overall Survival/OS Via a Log Rank Test.
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
Population: N/A - data were not collected
Secondary
To Determine the Role of CT Volumetric Analysis Compared to Standard Unidimensional CT in This Patient Population.
Time frame: conclusion of study
Population: N/A - Data were not collected