Overview
Rituximab, Lenalidomide, and Bortezomib in Mantle Cell Lymphoma
Status:
Completed
Completed
Trial end date:
2016-11-01
2016-11-01
Target enrollment:
0
0
Participant gender:
All
All
Summary
This is a Phase I/II multicenter, open-label, dose-escalation study of rituximab, bortezomib, and lenalidomide in the first-line or second-line treatment of patients with Mantle Cell Lymphoma (MCL).Phase:
Phase 1/Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
SCRI Development Innovations, LLCCollaborators:
Celgene
Celgene Corporation
Millennium Pharmaceuticals, Inc.Treatments:
Bortezomib
Lenalidomide
Rituximab
Thalidomide
Criteria
Inclusion Criteria:1. All study participants must be registered into the Mandatory Revlimid Risk Evaluation
and Mitigation Strategies (REMS) Program, and be willing and able to comply with the
requirements of the REMS program.
2. Histology: biopsy-proven mantle cell lymphoma (MCL).
3. Prior therapy: both newly diagnosed patients and relapsed or refractory patients who
have received one prior therapy are eligible. Patients who have previously received
high-dose chemotherapy with peripheral stem cell support are eligible.
4. Presence of at least one lymph node evaluable or mass measurable for response.
5. Platelets ≥ 75,000/µL and absolute neutrophil count (ANC) ≥ 1,000/µL within 14 days of
study registration (unless the treating physician deems the neutropenia is related to
bone marrow involvement, then an ANC of > 750/mm3 is allowed).
6. Renal function assessed by calculated creatinine clearance between ≥ 30 ml/min and
˂60ml/min by the Cockcroft-Gault method within 14 days of study registration
7. Total bilirubin ≤ 1.5x upper limit of normal (ULN), aspartate transaminase (AST)
(SGOT) and alanine transaminase (ALT) (SGOT) ≤ 3 x ULN
8. Eastern Cooperative Oncology Group (ECOG) performance of 0, 1, or 2.
9. Recovery from any previous treatment therapy.
10. Females of childbearing potential (FCBP) must adhere to the scheduled pregnancy
testing required in the Revlimid REMS® program, must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior and
again within 24 hours of starting lenalidomide for Cycle 1 (prescriptions must be
filled within 7 days as required by Revlimid REMS Program) and must either commit to
continued abstinence from heterosexual intercourse or begin two acceptable methods of
birth control, one highly effective method and one additional effective method at the
same time, at least 28 days before she starts taking lenalidomide. FCBP must also
agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual
contact with a FCBP even if they have had a successful vasectomy.
11. All study participants must be registered into the mandatory Revlimid REMS® program,
and be willing and able to comply with the requirements of Revlimid REMS® program.
12. Ability to understand and willingness to voluntarily sign a written informed consent
document before performance of any study-related procedure not part of normal medical
care, with the understanding that consent may be withdrawn by the subject at any time
without prejudice to future medical care.
Exclusion Criteria:
1. Patient has >1.5 x ULN total bilirubin.
2. Peripheral neuropathy ≥ CTCAE grade 2.
3. Relapsed or refractory patients who have received more than one prior therapy.
4. Pregnant or breastfeeding females. (Lactating females must agree not to breastfeed
while taking lenalidomide.)
5. Female patients who have a positive serum pregnancy test during the screening period,
or a positive urine pregnancy test on Day 1 before first dose of study drug, if
applicable.
6. Thrombolic or embolic events (such as a cerebrovascular accident, including transient
ischemic attacks) within the past 6 months.
7. Pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 within 28 days of the first dose
of study drug.
8. Any other hemorrhage/bleeding event ≥ CTCAE grade 3 ≤ 28 days of the first dose of
study drug
9. Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI
of the brain to exclude brain metastasis.
10. Central nervous system (CNS) involvement by lymphoma at time of enrollment.
11. Other medical conditions or psychiatric illness that would potentially interfere with
patient participation in this trial.
12. A second malignancy, other than basal cell carcinoma of the skin or in situ carcinoma
of the cervix, unless the tumor was treated with curative intent at least 2 years
previously.
13. Previous evidence of hypersensitivity to bortezomib, boron, mannitol, thalidomide,
(and development of erythema nodosum if characterized by a desquamating rash), or
rituximab (true anaphylaxis, not a rituximab-infusion reaction).
14. Known human immunodeficiency virus (HIV) infection or chronic hepatitis A, B, or C.
Patients who are HIV positive or who are positive for chronic hepatitis A, B, or C
will be excluded due to increased risk for bone marrow suppression and other
toxicities.
15. Active, clinically serious infection > CTCAE grade 2. Patients may be eligible upon
resolution of the infection.
16. Evidence or history of bleeding diathesis or coagulopathy.
17. Major surgery, open biopsy, or significant traumatic injury within 28 days of the
first dose of study drug.
18. Use of any other standard chemotherapy, radiation therapy, or experimental drug for
the treatment of MCL within 28 days of starting treatment.
19. Any condition that impairs a patient's ability to swallow whole pills. Impairment of
gastrointestinal function (GI) or GI disease that may significantly alter the
absorption of lenalidomide (e.g., ulcerative disease, uncontrolled nausea, vomiting,
diarrhea, malabsorption syndrome, or small bowel resection).
20. Patients with grade 3/4 cardiac problems, as defined by the New York Heart Association
(NYHA) criteria or any of the following:
- History of uncontrolled or symptomatic angina
- History of arrhythmias requiring medications, or clinically significant, with the
exception of asymptomatic atrial fibrillation requiring anticoagulation
- Myocardial infarction < 6 months from study entry
- Uncontrolled or symptomatic congestive heart failure
- Ejection fraction below the institutional normal limit
- Electrocardiographic evidence of acute ischemia or active conduction system
- Any other cardiac condition that, in the opinion of the treatment physician,
would make this protocol unreasonably hazardous for the patient
- Prior to study entry, any ECG abnormality at screening has to be documented by
the investigator as not medically relevant.
21. Uncontrolled hypertension (systolic blood pressure [BP] > 180 or diastolic BP > 100mm
Hg) or uncontrolled cardiac arrhythmias.
22. Any prior use of lenalidomide.