ClinicalTrials.gov processed this data on March 28, 2024Link to the current ClinicalTrials.gov record.https://clinicaltrials.gov/ct2/show/NCT01049945MMRC-020-021NCI-2009-01535MMRC-020-02109-004211C18083/6125NCT01049945NCT04567862Bendamustine Hydrochloride, Lenalidomide, and Dexamethasone in Treating Patients With Relapsed Multiple MyelomaA Phase I/II, Multicenter, Open-label, Dose-escalation Study of Bendamustine in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed Multiple MyelomaMayo ClinicOtherYes
RATIONALE: Drugs used in chemotherapy, such as bendamustine hydrochloride and dexamethasone,
work in different ways to stop the growth of cancer cells, either by killing the cells or by
stopping them from dividing. Lenalidomide may stimulate the immune system in different ways
and stop cancer cells from growing. Giving bendamustine hydrochloride together with
lenalidomide and dexamethasone may kill more cancer cells. PURPOSE: This phase I/II trial is
studying the side effects and best dose of bendamustine hydrochloride and lenalidomide when
given together with dexamethasone and to see how well they work in treating patients with
relapsed multiple myeloma.
PRIMARY OBJECTIVES: I. To determine the Maximum Tolerated Dose (MTD) of bendamustine and
lenalidomide in combination with dexamethasone in subjects with Multiple Myeloma (MM) in
first or second relapse. (Phase I) II. To evaluate the confirmed response rate of
bendamustine in combination with lenalidomide and dexamethasone in subjects with MM in first
or second relapse. (Phase II) SECONDARY OBJECTIVES: I. To evaluate the safety of bendamustine
in combination with lenalidomide and dexamethasone. (Phase I and II) II. To evaluate
time-to-tumor-progression, progression-free survival, duration of response, and overall
survival. (Phase II) OUTLINE: This is a phase I dose escalation study of bendamustine
hydrochloride and lenalidomide followed by a phase II study. Patients receive dexamethasone
orally or IV on days 1, 8, 15, and 22; bendamustine hydrochloride IV over 30 minutes on days
1 and 2; and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6
courses in the absence of disease progression or unacceptable toxicity. Patients achieving at
least stable disease after 6 courses may continue to receive lenalidomide and dexamethasone
as above in the absence of disease progression or unacceptable toxicity. Dexamethasone may be
discontinued after 12 courses of therapy at the treating investigator's discretion. After
completion of study treatment, patients are followed at 4 weeks and then periodically for up
to 2 years.
CompletedFebruary 2010September 16, 2015November 2012Phase 1/Phase 2InterventionalNoN/ASingle Group AssignmentTreatmentNone (Open Label)Dose Limiting Toxicity of Bendamustine Hydrochloride and Lenalidomide in Combination With Dexamethasone (Phase I)One cycle of treatmentThe Maximum Tolerated Dose (MTD) is the dose level below that at which a dose limiting toxicity (DLT) is observed in ≥ 33% (i.e., ≥ 2 of 6) subjects in a cohort. A dose limiting toxicity is defined as one of the following adverse events in the Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 deemed at least possibly related to treatment:
Grade 2 neuropathy with pain
Any grade 3 Non-Hematologic toxicity
Any grade Non-Hematologic event requiring a dose reduction in cycle 1 or delaying the next cycle by >14 days.
Grade 4 neutropenia
Febrile neutropenia
Grade 4 thrombocytopenia
Grade 3 thrombocytopenia associated with bleeding
Any Hematologic event requiring a dose reduction in cycle 1 or a delay in the next cycle of treatment by >14 days.
We are reporting the results of this endpoint as the number of DLTs per dose level.Confirmed Response Rate (Dose Level 4) Reported as the Percentage of Patients Achieving a Confirmed Response (sCR, CR, VGPR, or PR).Up to 6 cycles of treatmentComplete response (CR)
- Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow.
Stringent complete response (sCR) - A CR plus normal FLC ratio and no clonal cells in bone marrow
Near complete response (nCR) A CR, with the persistence of original monoclonal protein
Very good partial response (VGPR)
- Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-component plus urine M-component <100 mg per 24 h
Partial response (PR)
≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h.
a ≥50% decrease in the difference between involved and uninvolved FLC levels
or a ≥50% reduction in plasma cells is required in place of M-protein, if ≥30% at baseline.Duration of Response (DOR) (Phase II)Up to 2 years from study completionDOR is the time from the date the patient's objective status is first noted to be PR or better to the earliest date of progression (PD=Increase of > 25% from lowest response value in Serum/Urine M-component) is documented. Treatment response was assessed using the International Myeloma Working Group uniform criteria. Complete response (CR)=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. Stringent complete response (sCR)=A CR plus normal FLC ratio and no clonal cells in bone marrow. Near complete response (nCR)=A CR, with the persistence of original monoclonal protein. Very good partial response (VGPR) =Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-component plus urine M-component <100 mg per 24 h, Partial response (PR)=≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h.Event Free Survival (Phase II)Up to 2 years from study completionThe event-free survival time is defined as the time from registration to disease progression (PD=Increase of > 25% from lowest response value in Serum/Urine M-component) while receiving bendamustine, lenalidomide, and dexamethasone, death due to any cause, or subsequent treatment for multiple myeloma. The distribution of event-free survival will be estimated using the method of Kaplan-Meier. Treatment response was assessed using the International Myeloma Working Group uniform criteria.Progression Free Survival (Phase II)Up to 2 years from study completionThe progression-free survival time is defined as the time from registration to disease progression (PD=Increase of > 25% from lowest response value in Serum/Urine M-component) while receiving bendamustine, lenalidomide, and dexamethasone or death due to any cause, whichever comes first. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. Treatment response was assessed using the International Myeloma Working Group uniform criteria.Overall Survival (Phase II)at 6 monthsThe overall survival time is defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier. The overall survival rate at 6 months is defined as the percentage of participants who are alive at 6 months.170Refractory Multiple MyelomaArm IExperimentalPatients receive dexamethasone orally or IV on days 1, 8, 15, and 22; bendamustine hydrochloride IV over 30 minutes on days 1 and 2; and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.Drugbendamustine hydrochlorideGiven IVArm Ibendamustin hydrochloridebendamustinecytostasan hydrochlorideRibomustinSDX-105TreandaDruglenalidomideGiven orallyArm ICC-5013IMiD-1RevlimidDrugdexamethasoneGiven orally or IVArm IAeroseb-DexDecadermDecadronDecasprayDMDXM
Inclusion:
- Diagnosis of MM and documentation of at least 1 prior therapy (induction therapy
followed by stem cell transplantation is considered one prior therapy) but not more
than two previous therapies
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again
within 24 hours of starting lenalidomide
- Men must agree to use a latex condom during sexual contact with a FCBP even if they
have had a successful vasectomy; all patients must be counseled at a minimum of every
28 days about pregnancy precautions and risks of fetal exposure
- Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use protected health information
- Able to take aspirin (325 mg) daily as prophylactic anticoagulation (patients
intolerant to ASA or at high risk of developing thrombosis may use warfarin or low
molecular weight heparin)
- AST (SGOT) and ALT (SGPT) =< 3.0 x upper limit of normal (ULN)
- Creatinine clearance >= 60 mL/min (Cockcroft-Gault calculation) for patients enrolled
in Phase 1 and Creatinine clearance >= 30 mL/min (Cockcroft-Gault calculation) for
patients enrolled in phase 2 portion
- Patients with measurable disease, defined by any of the following: serum monoclonal
protein >= 1.0 g by protein electrophoresis; > 200 mg of monoclonal protein in the
urine on 24-hour electrophoresis; serum immunoglobulin free light chain >= 10 mg/dL
AND abnormal serum immunoglobulin kappa to lambda free light chain ratio; or
monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)
- All necessary baseline studies for determining eligibility must be obtained within 21
days prior to enrollment
- Subject has an ECOG =< 2 OR Karnofsky >= 60% performance status; patients with lower
performance status based solely on bone pain secondary to multiple myeloma will be
eligible
- FCBP 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
- Absolute neutrophil count (ANC) >= 1,000 cells/dL (1.0 x 10^9/L) (growth factors
cannot be used within 14 days of first drug administration)
- Untransfused platelet count >= 75,000 cells/dL (50 x 10^9/L) for patients in whom <
50% of bone marrow nucleated cells are plasma cells; but platelet count >=50,000/dL
for patients in whom 50% of bone marrow nucleated cells are plasma cells
- Total Bilirubin =< 1.5 mg/dL
- Hemoglobin >= 8.0 g/dl
Exclusion:
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the
exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
- Patients may be receiving concomitant therapy with bisphosphonates and low dose
corticosteroids (e.g., prednisone up to but no more than 10 mg p.o. q.d. or its
equivalent) for symptom management and comorbid conditions; doses of corticosteroid
should be stable for at least 7 days prior to study treatment
- Prior radiation therapy within 2 weeks of the first dose of study treatment
- Known active infection requiring parenteral or oral anti-infective treatment
- Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or
confuse follow-up evaluation
- Patient has hypersensitivity to any of the components of study therapy - Known HIV or
active hepatitis B or C viral infection
- Known hypersensitivity to required prophylactic medications
- Patient has received other investigational drugs within 14 days before enrollment
- Pregnant or breast-feeding females (lactating females must agree not to breast feed
while taking lenalidomide)
- Subjects with evidence of mucosal or internal bleeding and/or platelet transfusion
refractory (i.e., unable to maintain a platelet count >= 50,000 cells/mm^3)
- Concurrent therapy with a marketed or investigational anticancer therapy
- Any medical conditions that, in the Investigator's opinion, would impose excessive
risk to the patient
- Other investigational agents are not to be used during the study
- Prior peripheral stem cell transplant within 12 weeks of the first dose of study
treatment
All18 YearsN/ANoShaji K. Kumar, M.D.Study ChairMayo ClinicVivek Roy, M.D.Principal InvestigatorMayo ClinicCity of HopeDuarteCalifornia91010United StatesMayo Clinic in FloridaJacksonvilleFlorida55904United StatesUniversity of ChicagoChicagoIllinois60637-1470United StatesMayo ClinicRochesterMinnesota55905United StatesWashington Universtiy School of MedicineSaint LouisMissouri63110United StatesUnited StatesApril 2016January 14, 2010January 14, 2010January 15, 2010March 23, 2015March 23, 2015March 30, 2015February 10, 2020February 10, 2020February 11, 2020SponsorMultiple MyelomaNeoplasms, Plasma CellDexamethasoneLenalidomideBendamustine Hydrochloride