Overview

This trial is active, not recruiting.

Condition multiple myeloma
Treatments velcade, cyclophosphamide, revlimid
Phase phase 2
Target proteasome
Sponsor Duke University
Collaborator Millennium Pharmaceuticals, Inc.
Start date December 2012
End date December 2015
Trial size 17 participants
Trial identifier NCT01729338, Millennium, Pro00038924

Summary

The primary purpose of this study is to estimate the overall response rate (ORR), defined as partial response (PR) or better at any time during induction therapy. The success of the therapy will be determined by ORR with strong consideration given to the secondary endpoints of tolerability, duration of response, and quality of life (QOL).

All patients will be treated with the same experimental regimen. Several novel features are being explored: the substitution of cyclophosphamide for melphalan; once weekly AND subcutaneous bortezomib instead of standard twice weekly, intravenous dosing; and alternating bortezomib and lenalidomide in maintenance.

The investigators hypothesize that this regimen will prove to be tolerable and effective in inducing and maintaining remission in a patient population that is historically very difficult to treat, namely Multiple Myeloma (MM) patients who are too elderly or suffer comorbidities, such as renal insufficiency, that otherwise complicate aggressive therapies like autologous stem-cell transplantation (ASCT). In short, the investigators view this as the "Multiple Myeloma trial for non-trial candidates."

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
INDUCTION (28-day cycles for 8 cycles): VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15 Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15 Dexamethasone 40 mg PO days 1,8 and 15 MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death): Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21 Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15
velcade bortezomib
Bortezomib induction: 1.3 mg/m2, given subcutaneously (SC) on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Bortezomib maintenance (even cycles [10,12,14, etc.]: 1.3 mg/m2, given SC on days 1 and 15. For patients who required VELCADE dose reductions during induction, the last administered mg/m2 dose of VELCADE will be the starting dose for maintenance, given on days 1 and 15. Maintenance cycles will last 28 days and continue indefinitely, until disease progression, lack of tolerability, or death. Patients who cannot tolerate SC VELCADE will be converted to the same dose, given intravenously (IV), per discretion of the treating physician.
cyclophosphamide
Cyclophosphamide: 300 mg/m2, given orally on days 1,8 and 15. Up to eight cycles lasting 28 days each will be administered. Patients will not receive any study drugs during the final week of each induction cycle. Patients who cannot swallow cyclophosphamide pills will be converted to the same dose, given intravenously (IV).
revlimid lenalidomide
Lenalidomide (odd cycles [9,11,13, etc.]: 10 mg, given orally on days 1-21. Maintenance cycles will last 28 days and continue indefinitely, until disease progression, lack of tolerability, or death. On even cycles, patients will be prescribed enough lenalidomide to take at home, as instructed, for one cycle. This will be prescribed through the mandatory RevlimidREMS® program. If a dose of lenalidomide is missed, it should be taken as soon as possible on the same day. If it is missed for the entire day, it should not be made up. Patients who take more than the prescribed dose of lenalidomide should be instructed to seek emergency medical care if needed and contact study staff immediately.

Primary Outcomes

Measure
Overall response rate (ORR) during induction therapy
time frame: Up to 8 months

Secondary Outcomes

Measure
Number of patients with any grade or severe adverse events, as a measure of tolerability and safety
time frame: Up to 3 years
Maximum depth of response during induction therapy
time frame: Up to 8 months
Maximum depth of response during maintenance therapy
time frame: Up to 3 years
Median time to response
time frame: Up to 8 months
Median duration of response
time frame: From date of first confirmed response until date of disease progression or up to 3 years
Median progression-free survival
time frame: Up to 3 years
Median overall survival
time frame: Up to 3 years
Quality of life
time frame: Up to 3 years
Functionality
time frame: Up to 3 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Voluntary written informed consent 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. - Age ≥18 years at the time of signing the informed consent form. - Able to adhere to the study visit schedule and other protocol requirements. - Multiple Myeloma (MM) diagnosed according to the following standard criteria (all three criteria must be met): - Monoclonal plasma cells in bone marrow ≥10% and/or presence of biopsy-proven plasmacytoma - Laboratory tests meet the levels specified in the protocol - Measurable disease requiring systemic therapy. - No prior systemic therapy or radiation therapy active against myeloma lasting more than four weeks duration. Any prior therapy must be completed a minimum of 21 days before starting study drugs. Enrollment of subjects who require radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy. - Karnofsky performance status (KPS) of ≥ 60% at study entry. - In order to obtain lenalidomide, patients must be registered into the mandatory RevlimidREMS® program during the maintenance phase of therapy, and be willing and able to comply with the requirements of RevlimidREMS® - Female subjects must be postmenopausal for at least 1 year before the screening visit or surgically sterilized. If females are of childbearing potential, they must adhere to required pregnancy testing; male and female subjects must use specified effective birth control methods. - Patients should receive concomitant therapy with bisphosphonates, regardless of the presence of bony lesions, although study physicians may use their discretion based on presence of renal insufficiency or other mitigating factors. Exclusion Criteria: - Abnormal laboratory tests within the ranges specified in the protocol - Serum creatinine will not be used to exclude patients. Patients on renal-replacement therapy (e.g., hemodialysis or peritoneal dialysis) will be eligible to participate. - Light-chain (AL) amyloidosis. Patients with secondary amyloidosis due to MM are eligible. - ≥ Grade 2 peripheral neuropathy - Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any Electrocardiography (ECG) abnormality at screening must be documented by the investigator as not medically relevant. - Hypersensitivity to VELCADE, boron, mannitol, or any other component of protocol therapy. - Female subject is pregnant or lactating. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (b- hCG) pregnancy test result obtained during screening as specified in section 7.11. - Female patients who are lactating or 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. - Serious medical or psychiatric illness likely to interfere with participation in this clinical study. - Diagnosed or treated for another malignancy within 2 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. - Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial. - Concurrent use of other anti-cancer agents or treatments - Known HIV positivity - Known active hepatitis A, B or C

Additional Information

Official title Phase II Subcutaneous VELCADE and Oral Cyclophosphamide-based Induction + Sequential VELCADE and Revlimid Maintenance for Newly Diagnosed Multiple Myeloma in Non-transplant Candidates: An Entirely Non-intravenous Regimen
Principal investigator Gwynn Long, MD
Description A total of 35 patients will be accrued to this single arm, open label, phase II trial over a period of about 18 months, studying induction chemotherapy with VELCADE, cyclophosphamide and dexamethasone administered on an attenuated dosing schedule to accommodate non-candidates for high-dose chemotherapy with autologous stem cell transplantation - an often frail patient population. Maintenance therapy will follow with alternating lenalidomide and VELCADE. All patients should receive antiviral (zoster) prophylaxis, and peptic ulcer prophylaxis is recommended. Aspirin and/or anticoagulation are left to study physician discretion. All patients will be treated with the same experimental regimen. Several novel features are being explored: the substitution of cyclophosphamide for melphalan; once weekly AND subcutaneous bortezomib instead of standard twice weekly, intravenous dosing; and alternating bortezomib and lenalidomide in maintenance. The overarching aim is to preserve efficacy while minimizing toxicity and inconvenience to this often frail patient population.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Duke University.
Location data was received from the National Cancer Institute and was last updated in October 2016.