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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Keryx / AOI Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00401011
First received: November 15, 2006
Last updated: February 7, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Multiple Myeloma in Relapse
Drug: Perifosine
Drug: Bortezomib
Drug: Dexamethasone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Keryx / AOI Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Phase I toxicities [ Time Frame: Every 3 weeks ] [ Designated as safety issue: No ]
  • Phase II response rate [ Time Frame: Every 3 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase II toxicities [ Time Frame: Every 3 weeks ] [ Designated as safety issue: No ]
  • correlative data [ Time Frame: Every 3 weeks ] [ Designated as safety issue: No ]

Enrollment: 84
Study Start Date: August 2006
Study Completion Date: July 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
All patients will received perifosine qhs 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
All patients will received perifosine qhs daily and Bortezomib IV on days 1, 4, 8, and 11 q 21 days. Patients will be evaluated at q 3 weeks.
Drug: Bortezomib
All patients will received perifosine qhs daily and Bortezomib IV on days 1, 4, 8, and 11 q 21 days. Patients will be evaluated at q 3 weeks.
Other Name: Velcade
Active Comparator: 2
All patients will received perifosine qhs 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 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 qhs and bortezomib IV on days 1, 4, 8, and 11 q 21 days.
Drug: Dexamethasone
All patients will received perifosine qhs 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 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 qhs and bortezomib IV on days 1, 4, 8, and 11 q 21 days.

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).
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:
  3. Any two of the major criteria.
  4. Major criterion 1 plus minor criterion b, c, or d.
  5. Major criterion 3 plus minor criterion a or c.
  6. Minor criteria a, b, and c or a, b, and d.
  7. Patients must have relapsed or refractory disease (refractory is defined as progression during treatment or within 60 days after the completion of treatment).
  8. Patients must have been previously treated with bortezomib. Patients may have received prior perifosine.
  9. Age >= 18 years at the time of signing informed consent document.
  10. 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.)
  11. Subject has an ECOG (Zubrod) performance status of 0 to 2.
  12. Subject must be able to adhere to the study visit schedule and other protocol requirements.
  13. Subject must understand and voluntarily sign an informed consent document.
  14. 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.

Exclusion Criteria:

  1. Renal insufficiency (serum creatinine levels > 3 mg/dL).
  2. 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.
  3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to perifosine (miltefosine or edelfosine).
  4. 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.
  5. Subjects with hemoglobin < 8.0 g/dL.
  6. Subjects with an absolute neutrophil count (ANC) <= 500 cells/mm3.
  7. Peripheral neuropathy of grade 3 or greater. Patients with painful grade 2 neuropathy are also excluded.
  8. Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count >= 50,000 cells/mm3).
  9. Previous history of intolerance of bortezomib or perifosine.
  10. 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.
  11. WCBP who are pregnant or breast-feeding or men and women who are not using adequate contraception.
  12. Plasma cell leukemia at time of study entry.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00401011

Sponsors and Collaborators
Keryx / AOI Pharmaceuticals, Inc.
Investigators
Principal Investigator: Paul Richardson, MD Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: Keryx / AOI Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00401011     History of Changes
Other Study ID Numbers: Perifosine 218
Study First Received: November 15, 2006
Last Updated: February 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Keryx / AOI Pharmaceuticals, Inc.:
Perifosine
Bortezomib
Dexamethasone
Relapsed or Refractory Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on August 27, 2014