Velcade + Cyclophosphamide in Newly Diagnosed Multiple Myeloma

NCT01729338 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: Pro00038924Millennium
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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."

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) During Induction Therapy

  Defined as percentage of patients achieving a partial response or better by International Myeloma Working Group (IMWG) standard criteria: IMWG: Complete Response (CR): negative immunofixation on the serum and urine, no soft tissue plasmacytomas and \<5% plasma cells in the bone marrow; stringent CR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; Very Good Partial Response: serum and urine M-protein detected by immunofixation but not electrophoresis, \>90% in serum M-protein+urine, M-protein level \<100 mg/24hour; Partial Response (PR): ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or \<200 mg/24hour.

  Up to 8 months

Secondary Outcomes (11)

• Severe Adverse Event Rate

  Up to 3 years

• Maximum Depth of Response During Induction Therapy

  Up to 8 months

• Maximum Depth of Response During Maintenance Therapy

  Up to 3 years

• Median Time to Response

  Up to 8 months

• Median Duration of Response

  From date of first confirmed response until date of disease progression or up to 3 years

Study Arms (1)

Velcade, cyclophosphamide, Revlimid

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

Drug: Velcade; Drug: Cyclophosphamide; Drug: Revlimid

Interventions

Velcade DRUG

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.

Also known as: bortezomib

Velcade, cyclophosphamide, Revlimid

Cyclophosphamide DRUG

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).

Velcade, cyclophosphamide, Revlimid

Revlimid DRUG

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.

Also known as: lenalidomide

Velcade, cyclophosphamide, Revlimid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Duke Cancer Institute: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Cyclophosphamide; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Gwynn Long
• Organization: Duke University Medical Center

gwynn.long@duke.edu

919-668-0838

Study Officials

• Gwynn Long, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2012
• First Posted: November 20, 2012
• Study Start: December 19, 2012
• Primary Completion: December 31, 2015
• Study Completion: December 31, 2016
• Last Updated: May 31, 2017
• Results First Posted: May 31, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)