AzTrials
AzTrials

Multiple MyelomaPhase 1/2NCT00401011

Safety & Efficacy Study of Perifosine + Bortezomib +/- Dexamethasone for Multiple Myeloma Patients

A Phase 1/2 study testing Perifosine, Bortezomib and Dexamethasone in people with Multiple Myeloma and Multiple Myeloma in Relapse, run by AEterna Zentaris.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a phase I/II study of perifosine in combination with bortezomib-with or without dexamethasone-for patients with relapsed or refractory multiple myeloma previously treated with bortezomib. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma, Multiple Myeloma in Relapse
What is being tested?
Perifosine, Bortezomib and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
84 participants
Where
No sites listed yet
Study dates
Aug 2006to Jul 2011
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • Subject was previously diagnosed with multiple myeloma based on standard diagnostic criteria, as follows.
  • Major criteria:
  • Plasmacytomas on tissue biopsy.
  • Bone marrow plasmacytosis (> 30% plasma cells).
  • Monoclonal immunoglobulin spike on serum electrophoresis immunoglobulin G (IgG) >3.5 g/dL or immunoglobulin A (IgA) > 2.0 g/dL; kappa or lambda light chain excretion > 1 g/day on 24 hour urine protein electrophoresis.
  • Minor criteria:
Show all 23Show fewer
  • Bone marrow plasmacytosis (10 to 30% plasma cells).
  • Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria.
  • Lytic bone lesions.
  • Normal IgM < 50 mg/dL, IgA < 100 mg/dL or IgG < 600 mg/dL.
  • Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:
  • Any two of the major criteria.
  • Major criterion 1 plus minor criterion b, c, or d.
  • Major criterion 3 plus minor criterion a or c.
  • Minor criteria a, b, and c or a, b, and d.
  • Patients must have relapsed or refractory disease (refractory is defined as progression during treatment or within 60 days after the completion of treatment).
  • Patients must have been previously treated with bortezomib. Patients may have received prior perifosine.
  • Age >= 18 years at the time of signing informed consent document.
  • All necessary baseline studies for determining eligibility must be obtained within 14 days prior to enrollment. (Pregnancy test must be within 7 days for women of childbearing potential.)
  • Subject has an ECOG (Zubrod) performance status of 0 to 2.
  • Subject must be able to adhere to the study visit schedule and other protocol requirements.
  • Subject must understand and voluntarily sign an informed consent document.
  • Women of child-bearing potential (WCBP)- must have a negative serum or urine pregnancy test within 72 hours prior to enrollment. In addition, all sexually active WCBP and male patients must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study.

Who cannot join

  • Renal insufficiency (serum creatinine levels > 3 mg/dL).
  • Patients who present with either ALT or AST >= 2.5 X upper limit of normal (ULN) and/or patients with bilirubin >= 1.5 X ULN.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to perifosine (miltefosine or edelfosine).
  • Concomitant medications that include corticosteroids (except as indicated for other medical conditions or up to 100 mgs of hydrocortisone or equivalent as premedication for administration of certain medications or blood products), chemotherapy, or other therapy that is or may be active against myeloma within 2 weeks prior to Cycle 1 Day 1. Nitrosoureas must be discontinued 6 weeks prior to Cycle 1 Day 1.
  • Subjects with hemoglobin < 8.0 g/dL.
  • Subjects with an absolute neutrophil count (ANC) <= 500 cells/mm3.
Show all 12Show fewer
  • Peripheral neuropathy of grade 3 or greater. Patients with painful grade 2 neuropathy are also excluded.
  • Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count >= 50,000 cells/mm3).
  • Previous history of intolerance of bortezomib or perifosine.
  • Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study.
  • WCBP who are pregnant or breast-feeding or men and women who are not using adequate contraception.
  • Plasma cell leukemia at time of study entry.

About this study

Official title: An Open-Label Phase I/II Study of the Safety and Efficacy of Perifosine and Bortezomib With or Without Dexamethasone for Patients With Relapsed or Refractory Multiple Myeloma Previously Treated With Bortezomib

This is a phase I/II study of perifosine in combination with bortezomib-with or without dexamethasone-for patients with relapsed or refractory multiple myeloma previously treated with bortezomib. The current protocol will enroll patients with relapsed or refractory multiple myeloma who have been previously treated with bortezomib. The patients will be treated with perifosine, 50 mg or 100 mg qhs, in combination with bortezomib to determine if there is any preliminary evidence that the addition of perifosine improves the outcome for these patients. Previous treatment with perifosine will be allowed in this study. Patients progressing on treatment with perifosine and bortezomib will receive dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 18, and 19 of each 21-day cycle in addition to bortezomib and perifosine.

Read the detailed description

The primary objective of the phase I portion is to determine the maximum tolerated dose of perifosine in combination with bortezomib in patients previously treated with bortezomib.

All patients will receive daily perifosine qhs with food. In the initial phase I study, 3 patients will be entered into a specified combination of perifosine and bortezomib cohorts. If no dose-limiting toxicity is observed, then three additional patients will be entered in cohort 4 - a full dose of bortezomib (1.3 mg/m2 on days 1, 4, 8 and 11 every 3 weeks). If this dose is tolerated it will be used for the phase II study, otherwise an intermediate dose of 1 mg/m2 on days 1, 4, 8, and 11 every 3 weeks will be employed.

The phase II study will use the maximum tolerated dose of bortezomib and perifosine. The primary objective of phase II portion is to determine the response rate (the combined CR + PR + MR) following treatment with perifosine + bortezomib in patients with multiple myeloma who have relapsed following initial front-line therapy, are refractory to their most recent therapy, and were previously treated with bortezomib. The secondary objectives of the phase II portion are;

  1. To further assess the safety and tolerability of perifosine in combination with bortezomib-with or without dexamethasone-in patients with multiple myeloma.
  2. To obtain correlative data in patients with multiple myeloma treated with perifosine in combination with bortezomib-with or without dexamethasone (NOTE Centers may choose not to participate in correlative studies).
Being tested
Perifosine, Bortezomib, Dexamethasone
Keywords
Perifosine, Bortezomib, Dexamethasone, Relapsed or Refractory Multiple Myeloma
Medical subject headings
Multiple Myeloma, Recurrence

What participants receive

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

  • PerifosineDrug

    Also called D-21266, KRX-0401

    Phase I: Patients will receive daily perifosine (doses 50 mg/m2 or 100 mg/m2) at bedtime.

    Phase II: All patients will receive daily perifosine at bedtime. Patients will be evaluated every 3 weeks.

  • BortezomibDrug

    Also called Velcade

    Phase I: Patients will receive 1 mg/m2 or 1.3 mg/m2 on days 1, 4, 8, and 11 every 3 weeks. Phase II: Patients will receive bortezomib on days 1,4,8 and 11 every 3 weeks.

  • DexamethasoneDrug

    Also called Dexa

    Phase II: If the patient shows progressive disease after 3 weeks, dexamethasone 20 mg will be added to perifosine and bortezomib on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 18, and 19 to perifosine at bedtime and bortezomib IV on days 1, 4, 8, and 11 q 21 days.

Study groups in NCT00401011
Study groupRoleWhat they receive
Phase II: Perifosine + BortezomibExperimentalAll patients will start with perifosine at bedtime daily and Bortezomib IV on days 1, 4, 8, and 11 q 21 days. Patients will be evaluated at q 3 weeks. If the patient has a CR, PR, MR or stable disease, they will continue treatment.
Receives: Drug: Perifosine; Drug: Bortezomib
Phase II: Perifosine + Bortezomib + DexaExperimentalIf the patient shows progressive disease, dexamethasone 20 mg will be added on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 18, and 19 to perifosine at bedtime and bortezomib IV on days 1, 4, 8, and 11 q 21 days.
Receives: Drug: Perifosine; Drug: Bortezomib; Drug: Dexamethasone
Phase I: Dose 1: Perifosine + BortezomibExperimentalPerifosine 50 mg at bedtime and bortezomib 1 mg/m2 on days 1, 4, 8, and 11 every 3 weeks.
Receives: Drug: Perifosine; Drug: Bortezomib
Phase I: Dose 2: Perifosine + BortezomibExperimentalPerifosine 100 mg at bedtime and bortezomib 1 mg/m2 on days 1, 4, 8, and 11 every 3 weeks
Receives: Drug: Perifosine; Drug: Bortezomib
Phase I: Dose 3: Perifosine + BortezomibExperimentalPerifosine 50 mg at bedtime and bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 every 3 weeks
Receives: Drug: Perifosine; Drug: Bortezomib
Phase I: Dose 4: Perifosine + BortezomibExperimentalPerifosine 100 mg at bedtime and bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 every 3 weeks
Receives: Drug: Perifosine; Drug: Bortezomib

What is being measured

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

  1. Phase I: Maximum Tolerated Dose (MTD). Phase II: To determine response rate.

    Phase I: To determine the MTD of perifosine in combination with bortezomib in patients previously treated with bortezomib.

    Phase II: The primary endpoint of the study was 6-month progression-free survival.

    Measured: Every 3 weeks

Secondary outcomes (2)

  1. Phase II: Tolerability and Safety

    To assess the safety and tolerability of perifosine in combination with bortezomib - with or without dexamethasone.

    Measured: Every 3 weeks

  2. Phase II: Correlative data

    To obtain correlative data in patients with multiple myeloma treated with perifosine in combination with bortezomib-with or without dexamethasone

    Measured: Every 3 weeks

Timeline

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

  1. First posted17 Nov 2006 (estimated)
  2. Study startAug 2006
  3. Primary completionDec 2010
  4. Study completionJul 2011

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
In the Phase I part, maximum tolerated dose (MTD) is determined in sequential cohorts of patients. All patients will start with perifosine and bortezomib (cf. arms and interventions). In case of progression, dexamethasone 20 mg will be added to treatment. Phase II: open-label single treatment arm.
Masking
None (open label)
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00401011
Sponsor's protocol ID
Perifosine 218
Status last verified
Feb 2012
First submitted
15 Nov 2006
Last updated
23 Feb 2018
Results posted
No
Data monitoring committee
No

Publications

  • Richardson PG, Wolf J, Jakubowiak A, Zonder J, Lonial S, Irwin D, Densmore J, Krishnan A, Raje N, Bar M, Martin T, Schlossman R, Ghobrial IM, Munshi N, Laubach J, Allerton J, Hideshima T, Colson K, Poradosu E, Gardner L, Sportelli P, Anderson KC. Perifosine plus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma previously treated with bortezomib: results of a multicenter phase I/II trial. J Clin Oncol. 2011 Nov 10;29(32):4243-9. doi: 10.1200/JCO.2010.33.9788. Epub 2011 Oct 11.

    PubMed 21990396

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Perifosine, Bortezomib and Dexamethasone in people with Multiple Myeloma and Multiple Myeloma in Relapse, run by AEterna Zentaris.

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 23 inclusion and 12 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: finished, as of the sponsor's last update on 23 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Phase I: Maximum Tolerated Dose (MTD). Phase II: To determine response rate. (time frame: Every 3 weeks). 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 NCT00401011, which also lists 1 linked publication.

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 23 Feb 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in