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

NCT00401011 | Completed Phase 1

• 1 other identifier: Perifosine 218
• Study Type: interventional
• Target: 84
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Multiple Myeloma; Multiple Myeloma in Relapse

Keywords

Perifosine; Bortezomib; Dexamethasone; Relapsed or Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (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.

  Every 3 weeks

Secondary Outcomes (2)

• Phase II: Tolerability and Safety

  Every 3 weeks

• Phase II: Correlative data

  Every 3 weeks

Study Arms (6)

Phase II: Perifosine + Bortezomib

EXPERIMENTAL

All 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.

Drug: Perifosine; Drug: Bortezomib

Phase II: Perifosine + Bortezomib + Dexa

EXPERIMENTAL

If 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.

Drug: Perifosine; Drug: Bortezomib; Drug: Dexamethasone

Phase I: Dose 1: Perifosine + Bortezomib

EXPERIMENTAL

Perifosine 50 mg at bedtime and bortezomib 1 mg/m2 on days 1, 4, 8, and 11 every 3 weeks.

Drug: Perifosine; Drug: Bortezomib

Phase I: Dose 2: Perifosine + Bortezomib

EXPERIMENTAL

Perifosine 100 mg at bedtime and bortezomib 1 mg/m2 on days 1, 4, 8, and 11 every 3 weeks

Drug: Perifosine; Drug: Bortezomib

Phase I: Dose 3: Perifosine + Bortezomib

EXPERIMENTAL

Perifosine 50 mg at bedtime and bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 every 3 weeks

Drug: Perifosine; Drug: Bortezomib

Phase I: Dose 4: Perifosine + Bortezomib

EXPERIMENTAL

Perifosine 100 mg at bedtime and bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 every 3 weeks

Drug: Perifosine; Drug: Bortezomib

Interventions

Perifosine DRUG

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.

Also known as: D-21266, KRX-0401

Phase I: Dose 1: Perifosine + Bortezomib; Phase I: Dose 2: Perifosine + Bortezomib; Phase I: Dose 3: Perifosine + Bortezomib; Phase I: Dose 4: Perifosine + Bortezomib; Phase II: Perifosine + Bortezomib; Phase II: Perifosine + Bortezomib + Dexa

Bortezomib DRUG

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.

Also known as: Velcade

Phase I: Dose 1: Perifosine + Bortezomib; Phase I: Dose 2: Perifosine + Bortezomib; Phase I: Dose 3: Perifosine + Bortezomib; Phase I: Dose 4: Perifosine + Bortezomib; Phase II: Perifosine + Bortezomib; Phase II: Perifosine + Bortezomib + Dexa

Dexamethasone DRUG

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.

Also known as: Dexa

Phase II: Perifosine + Bortezomib + Dexa

Eligibility Criteria

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

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AEterna Zentaris: lead

Related Publications (1)

• 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.

  PMID: 21990396 RESULT

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

perifosine; Bortezomib; Dexamethasone; Absorptiometry, Photon

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Radiography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Densitometry; Photometry; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Paul Richardson, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 15, 2006
• First Posted: November 17, 2006
• Study Start: August 1, 2006
• Primary Completion: December 1, 2010
• Study Completion: July 1, 2011
• Last Updated: February 23, 2018

Record last verified: 2012-02