Mantle Cell Lymphoma, Untreated
Conditions
Keywords
Lenalidomide, 15-196
Brief summary
The purpose of this study is to find out what effects, good and/or bad, the treatment including 1) Lenalidomide-RCHOP, 2) R-HIDAC, and 3) Lenalidomide-Rituximab maintenance has on the participant and their lymphoma.
Detailed description
Patients will receive lenalidomide 15 mg orally daily on days 1-14 with standard-dose R-CHOP (375 mg/m\^2 intravenous rituximab, 750 mg/m2 intravenous cyclophosphamide, 50 mg/m\^2 intravenous doxorubicin, and 1.4 mg/m2 intravenous vincristine on day 1, and 100 mg prednisone days 1-5 or days 2-6) every 21 days for four cycles. All patients will receive pegfilgrastim on day 2 of each cycle and aspirin 81 mg orally daily for venous thromboembolism prophylaxis throughout the four cycles. After four cycles of Len-RCHOP, the patients will undergo restaging PET/CT scans. Patients with evidence of disease progression will be treated off study. R-HIDAC After lenalidomide-RCHOP phase, patients without evidence of progressive disease will receive rituximab 375 mg/m\^2 day 1 and then patients will be admitted for high-dose cytarabine (HIDAC). Recommended age-adjusted HIDAC doses are as follows: ≤65 years: 3 g/m2 every12 hours X 4 doses; 65-70 years: 2 g/m\^2 every12 hours X 4 doses; \>70 years: 1 g/m\^2 every12 hours X 4 doses. Physician discretion will dictate the choice of HIDAC dose, ranging from 1 g/m\^2 - 3 g/m\^2 every 12 hours X 4 doses. Patients will receive two cycles of rituximab-HIDAC every 3 weeks. After two cycles of R-HIDAC, the patients will undergo restaging PET/CT scans. Patients with evidence of disease progression will be treated off study. Len-Rituximab Maintenance After completion of induction chemotherapy with Len-RCHOP and R-HIDAC, patients will begin maintenance phase with lenalidomide and rituximab for 6 months. Lenalidomide will be administered at 15 mg orally daily on days 1-21 of a 28-day cycle for a total of 6 cycles and rituximab maintenance every 8 weeks for a total of 3 treatments.
Interventions
DRUGLenalidomide
DRUGR-CHOP
* Rituximab 375 mg/m\^2 IVPB with premedications Day 1 * Cyclophosphamide 750 mg/m\^2 IVPB Day 1 * Doxorubicin 50 mg/m\^2 IVP Day 1 * Vincristine 1.4 mg/m\^2 IVP (capped at 2 mg) Day 1 * Prednisone 100 mg PO Daily on Days 1-5 or 2-6
DRUGhigh-dose cytarabine (HIDAC)
Sponsors
Celgene Corporation
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previously untreated mantle cell lymphoma patients (at least clinical stage 2) * Histologic diagnosis confirmed by MSKCC pathologist as mantle cell lymphoma * Presence of evaluable disease * Age ≥18 years KPS ≥ 70% * Adequate organ function: ANC ≥1500 and platelet count ≥100,000, unless felt to be secondary to underlying mantle cell lymphoma * Renal function assessed by calculated creatinine clearance as follows: * Cockcroft-Gault estimation of CrCl): * Calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula. See section below, Dosing Regimen, regarding lenalidomide dose adjustment for calculated creatinine clearance ≥30ml/min and \< 60ml/min. * Adequate hepatic function as determined by * Total bilirubin \<1.5X upper limit of normal (ULN) (unless known Gilbert syndrome) * AST (SGOT) and ALT (SGPT) 3 x ULN * All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program. * Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. * Each subject must sign an informed consent form indicating that he or she understand the purpose of and procedures required for the study and are willing to participate. * Short course systemic corticosteroids is permissible for disease control, improvement of performance status or non-cancer indication if ≤ 10 days and must be discontinued prior to study treatment.
Exclusion criteria
* Known central nervous system (CNS) lymphoma * Uncontrolled or severe cardiovascular disease or left ventricular ejection fraction \<50% as determined by echocardiogram or MUGA. * Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk. * Pregnant or breast-feeding. Pre-menopausal patients must have a negative serum HCG within 14 days of enrollment. * Patients using ≥20 mg/day of prednisone (or steroid equivalent dose) for any chronic medical condition * Known seropositive, requiring anti-viral therapy, and with detectable viral load by PCR for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). * Known hypersensitivity to thalidomide or lenalidomide * The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. * Patients planned for upfront consolidation with high-dose therapy and autologous stem cell transplant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3-year Progression-free Survival (PFS) | 3 years | acceptable 3-yr PFS as 75% or higher, and unacceptable rate as 60% or lower. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy Lenalidomide + R-CHOP x 4 cycles R-HiDAC x 2 cycles R-Len maintenance x 6 months. | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Chemotherapy |
|---|---|
| Age, Continuous | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 46 Participants |
| Region of Enrollment United States | 49 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 18 / 49 |
| other Total, other adverse events | 44 / 49 |
| serious Total, serious adverse events | 27 / 49 |
Outcome results
Primary
3-year Progression-free Survival (PFS)
acceptable 3-yr PFS as 75% or higher, and unacceptable rate as 60% or lower.
Time frame: 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy | 3-year Progression-free Survival (PFS) | 63 % of pts progression-free survival |