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Multiple MyelomaPhase 2NCT01729338

Velcade + Cyclophosphamide in Newly Diagnosed Multiple Myeloma

A Phase 2 study testing Velcade, Cyclophosphamide and Revlimid in people with Multiple Myeloma, run by Duke University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Velcade, Cyclophosphamide and Revlimid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
19 Dec 2012to 31 Dec 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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
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  • 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.

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

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

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."

Read the detailed 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.

Being tested
Velcade, Cyclophosphamide, Revlimid
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VelcadeDrug

    Also called 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.

  • CyclophosphamideDrug

    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).

  • RevlimidDrug

    Also called 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.

Study groups in NCT01729338
Study groupRoleWhat they receive
Velcade, cyclophosphamide, RevlimidExperimentalINDUCTION (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
Receives: Drug: Velcade; Drug: Cyclophosphamide; Drug: Revlimid

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 8 months

Secondary outcomes (11)

  1. Severe Adverse Event Rate

    Defined as number of patients experiencing any grade or severe (≥ grade 3 by common toxicity criteria for adverse events (CTCAE) v4.0 criteria) adverse events at any time during the study

    Measured: Up to 3 years

  2. Maximum Depth of Response During Induction Therapy

    Maximum depth of response is defined as: ranging from partial response to complete response by International Myeloma Working Group (IMWG). Described as number of patients achieving each level of response. IMWG: CR: negative immunofixation on the serum and urine, no soft tissue plasmacytomas and <5% plasma cells in the bone marrow; sCR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR: serum and urine M-protein detected by immunofixation but not electrophoresis, >90% in serum M-protein+urine, M-protein level <100 mg/24hour; PR: ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or <200 mg/24hour. Stable disease mean that the patient has not achieved CR, VGPR, PR or progressive disease.

    Measured: Up to 8 months

  3. Maximum Depth of Response During Maintenance Therapy

    Defined as maximum depth of response (ranging from partial response to complete response by International Myeloma Working Group (IMWG) criteria at any point during post-induction maintenance therapy.

    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. Stable disease mean that the patient has not achieved CR, VGPR, PR or progressive disease.

    Measured: Up to 3 years

  4. Median Time to Response

    Defined as median time to achievement of response (partial remission or better by International Myeloma Working Group standard criteria), in study subjects during 8 months of induction chemotherapy.

    Measured: Up to 8 months

  5. Median Duration of Response

    Defined as median time elapsed in study subjects between achievement of response and disease progression.

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

  6. Median Progression-free Survival

    Defined as median time elapsed in study subjects between initiation of study therapy and either disease progression or death, regardless of cause of death.

    Measured: 4 years

  7. Median Overall Survival

    Defined as median time elapsed in study subjects between initiation of study therapy and death, regardless of cause.

    Measured: Up to 3 years

  8. QLQ-C30 Question 29

    Measured as mean quality of life in study subjects, quantitatively scored using the standardized and validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Question 29: how would you rate your overall health during the past week? 7 point scores are standardized to a scale of 0-100, where 100 means highest possible quality.

    Measured: baseline, 3 months, 5 months

  9. QLQ-C30 Question 30

    Measured as mean quality of life in study subjects, quantitatively scored using the standardized and validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Question 30: How would you rate your overall quality of life during the past week?

    7 point scores are standardized to a scale of 0-100, where 100 means highest possible quality.

    Measured: baseline, 3 months, 5 months

  10. Functionality as Assessed Using the Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool

    Mean functionality in study subjects, quantitatively scored using the standardized and validated Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool, which comprehensively assesses aspects of a patient's functionality such as symptoms (e.g., pain, anxiety), social support (e.g., someone to turn to for help), and ability to carry out routine activities (e.g., grocery shopping) or physical exertion (e.g., climbing stairs) was assessed at baseline.

    The score is obtained by inserting patient-specific data into the online calculator found at http://www.mycarg.org/Chemo_Toxicity_Calculator, which is based on the risk score described in Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457-3465.

    The risk score ranges from 0-19, with 0-5 indicating low risk, 6-9 intermediate risk, and 10-19 high risk for severe (grade >2) toxicity.

    Measured: baseline

  11. Risk Score as Assessed Using the Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool

    Calculation of the risk score requires that the patient be assessed with the CALGB Assessment Tool, which has both a patient self-reporting questionnaire and a clinician assessment. Both will be used in this trial, and thus patients will have risk scores based on their own self-assessments and risk scores based on the clinicians' assessment. The risk score ranges from 0-19, with 0-5 indicating low risk, 6-9 intermediate risk, and 10-19 high risk. The distribution of the risk score in this trial will be described by plotting the median of the risk score against time, with patient and clinician assessments overlaid on the same plot.

    Measured: Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Nov 2012 (estimated)
  2. Study start19 Dec 2012
  3. Primary completion31 Dec 2015
  4. Study completion31 Dec 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01729338
Sponsor's protocol ID
Pro00038924
Other IDs
Millennium
Status last verified
Apr 2017
First submitted
14 Nov 2012
Last updated
31 May 2017
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Velcade, Cyclophosphamide and Revlimid in people with Multiple Myeloma, run by Duke University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 31 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) During Induction Therapy (time frame: Up to 8 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01729338.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2017.

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