Phase II Study of Subcutaneous (SC) Bortezomib, Lenalidomide and Dexamethasone for Relapsed and/or Refractory Multiple Myeloma; Followed by SC Bortezomib Maintenance
Background:
- Multiple myeloma (MM) is an incurable plasma cell neoplasm with a median survival of
3-4 years.
- Increased survival has been achieved with the introduction of the proteasome inhibitor
bortezomib and immunomodulatory drugs (IMiDs) such as lenalidomide. Bortezomib and
lenalidomide have different but overlapping mechanism of anti-MM activity in
preclinical studies.
- Despite the benefits of novel agents, bortezomib and lenalidomide pose clinical
challenges. Bortezomib drug toxicity includes neuropathy, GI distress, myelosuppression
and herpes zoster reactivation. Together with lenalidomide, the incidence of sensory
neuropathy reaches 80%.
- Subcutaneous (SC) Bortezomib was evaluated in a prospective phase I trial for relapsed
and/or refractory MM. SC administration was found to be comparable with the established
IV route, with no differences in overall systemic availability and pharmacodynamic
activity, similar toxicity profiles, and similar response rates.
- Combining SC, rather than IV bortezomib, with lenalidomide and dexamethasone is
especially attractive given the potential for less overall neurotoxicity and improved
convenience for the patient.
- Also, using bortezomib SC as a maintenance therapy after combination therapy is a novel
strategy that has the potential to set the stage for coming oral proteasome inhibitors
as potential maintenance strategies in the future.
Objectives:
Primary Objective
- Determine response rates, of S.C. bortezomib, lenalidomide, and dexamethasone (VRd) in
relapse and/or refractory MM patients
Secondary Objectives
- Assess peripheral blood for immune cell populations in relation to SC bortezomib
maintenance
- Evaluate toxicity, including peripheral neuropathy
- Evaluate patterns of change in patient-reported quality of life and symptom distress
- Gauge the feasibility, responsiveness to change and associated effect sizes when using
patient-reported outcomes to augment clinician ratings of regimen-related treatment
toxicity, including incidence and severity of peripheral neuropathy
- Determine duration of response
- Determine progression free survival
Eligibility:
- Patients with histologically confirmed relapsed and/or refractory multiple myeloma
- Age greater than or equal to 18 years
- Without serious co-morbidity that would interfere with receipt of VRd
- If patient has neuropathy, it must be less than or equal to Grade 1 at the time of
first dose or within 14 days of enrollment
- Absolute neutrophil count (ANC) greater than equal to 1.0 K/uL, hemoglobin less than or
equal to 8 g/dL, and platelet count greater than or equal to 75 K/uL
- Adequate hepatic function, with bilirubin < 1.5 times ULN; AST and ALT < 3.0 times
ULN
- Creatinine Clearance greater than or equal to 60 ml/min. CrCl will be calculated by
Cockcroft-Gault method. CrCl (calculated) = (140 - Age) times Mass (in kilograms) times
[0.85 if Female] 72 times Serum Creatinine (in mg/dL). If calculated CrCl based on
Cockcroft-Gault method is < 60 mL/min, patient will have a 24 hr urine collection to
measure CrCl. The measured CrCl must also be greater than or equal to 60 ml/min for the
patient to be eligible.
Design:
Patient will receive treatment in this single arm study for 8 total cycles (each cycle is 21
days) with the following drugs, dosages and schedule:
- Bortezomib
Cycle 1-8: 1.0 mg/m(2) SC at a concentration of 2.5 mg/ml to the thighs or abdomen on days
1, 4, 8, 11 of 21 day cycle
- Lenalidomide
Cycle 1: 15 mg oral daily on days 2-14 of 21 day cycle
Cycle 2-8: 15 mg oral daily on days 1-14 of 21 day cycle
- Dexamethasone
Cycle 1: 10 mg oral on days 2,4,5,8,9,11,12 of 21 day cycle
Cycle 2-8: 10 mg oral on days 1,2,4,5,8,9,11,12 of 21 day cycle
- Maintenance therapy
After completion of cycle 8, patients with greater than or equal to stable disease will
receive maintenance with bortezomib S.C. at a dose per end of Cycle 8. Maintenance will be
given on days 1 and 15 of a 28 day cycle, and will continue until progression or
unacceptable toxicity.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall Response Rate
2 years
No
Carl O Landgren, M.D.
Principal Investigator
National Cancer Institute (NCI)
United States: Federal Government
120169
NCT01647165
July 2012
June 2015
Name | Location |
---|---|
National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |