Efficacy of Perifosine Alone and in Combination With Dexamethasone for Patients With Multiple Myeloma

Sponsor

AEterna Zentaris (Industry)

Overall Status

Completed

CT.gov ID

NCT00375791

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

9.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 2 study of perifosine in patients with multiple myeloma. Patients will receive perifosine 150 mg at bedtime (qhs) daily. Patients will be assessed by serum and/or urine-electrophoresis at least every 3 weeks.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: perifosine Drug: dexamethasone	Phase 2

Detailed Description

Treatment: Patients will take three 50 mg tablets of perifosine qhs daily with food. All patients should continue therapy unless disease progression is documented on two occasions at least 1 week apart. Progressing patients will have dexamethasone 20 mg twice per week added to the perifosine. Patients who experience toxicity may continue on treatment with doses delayed or reduced.

Evaluations: Serum and/or urine-electrophoresis will be evaluated for progression or response at 3 week intervals.

This study will enroll a total of up to 64 patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

67 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label Phase II Study of the Safety and Efficacy of Perifosine Alone and in Combination With Dexamethasone for Patients With Relapsed or Relapsed/Refractory Multiple Myeloma

Study Start Date :

Dec 1, 2005

Actual Primary Completion Date :

Dec 1, 2010

Actual Study Completion Date :

Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Perifosine daily Patients will take three 50 mg tablets of perifosine daily at bedtime with food. Patients will be examined every three weeks. If patients have no progression it is allowed to receive 8 cycles of perifosine	Drug: perifosine 100 - 150 mg daily Other Names: D-21266 KRX-0401
Experimental: Perifosine daily + Dexa twice per week Patients will take three 50 mg tablets of perifosine daily at bedtime with food until progression. If progressive disease is confirmed by a second measurement at least one week later the patient will receive a combination of 20 mg twice per week dexamethasone (dexa) and 150 mg perifosine daily at bedtime.	Drug: perifosine 100 - 150 mg daily Other Names: D-21266 KRX-0401 Drug: dexamethasone 20 mg twice weekly Other Names: decadron

Arm

Intervention/Treatment

Experimental: Perifosine daily

Patients will take three 50 mg tablets of perifosine daily at bedtime with food. Patients will be examined every three weeks. If patients have no progression it is allowed to receive 8 cycles of perifosine

Drug: perifosine

100 - 150 mg daily

Other Names:

D-21266

KRX-0401

Experimental: Perifosine daily + Dexa twice per week

Patients will take three 50 mg tablets of perifosine daily at bedtime with food until progression. If progressive disease is confirmed by a second measurement at least one week later the patient will receive a combination of 20 mg twice per week dexamethasone (dexa) and 150 mg perifosine daily at bedtime.

Drug: perifosine

100 - 150 mg daily

Other Names:

D-21266

KRX-0401

Drug: dexamethasone

20 mg twice weekly

Other Names:

decadron

Outcome Measures

Primary Outcome Measures

Response rate (the combined CR + PR + MR) with treatment perifosine [Every 3 weeks]
To determine the response rate (the combined Complete Response (CR) + Partial Response (PR) + Minor Response (MR) following treatment with perifosine in patients with multiple myeloma who have relapsed following Initial front-line therapy and are refractory to their most recent therapy.

Secondary Outcome Measures

Response rate (CR + PR + MR) with combination therapy [Every 3 weeks]
To determine the response rate (CR + PR + MR) following treatment with combination therapy with perifosine plus dexamethasone in patients with multiple myeloma who have relapsed or were refractory to their most recent therapy before study enrollment, and failed to respond to or have relapsed following treatment with perifosine alone.
Assess the safety and tolerability of perifosine alone and in combination [Every 3 weeks]
To assess the safety and tolerability of perifosine alone and in combination with dexamethasone in patients with multiple myeloma.
Obtain correlative data in patients with multiple myeloma treated with perifosine and in combination [Every 3 weeks]
To obtain correlative data in patients with multiple myeloma treated with perifosine alone and in combination with dexamethasone.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 immunoglobulin M (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.

Exclusion Criteria:

Renal insufficiency (serum creatinine levels > 3 mg/dL).
Patients who present with either ALT or AST ≥ 2.5 X upper limit of normal.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to perifosine (miltefosine or edelfosine).
Concomitant therapy medications that include corticosteroids (except as indicated for other medical conditions, or up to 100 mgs of hydrocortisone as premedication for administration of certain medications or blood products) or other chemotherapy that is or may be active against myeloma, or therapy with chemotherapy within 3 weeks prior to Day 1. Nitrosoureas must be discontinued 6 weeks prior to Day 1.
Subjects with a hemoglobin < 8.0 g/dL.
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.
Women of childbearing potential (WCBP) who are pregnant, or breast-feeding or men and women who are not using adequate contraception are excluded.
Plasma cell leukemia.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigative Site	Berkeley	California	United States	94704
2	Investigative Site	Duarte	California	United States	91010
3	Investigative Site	Atlanta	Georgia	United States	30322
4	Investigative Site	Chicago	Illinois	United States	60611
5	Investigative Site	Boston	Massachusetts	United States	02115
6	Investigative Site	Ann Arbor	Michigan	United States	48103
7	Investigative Site	Charlottesville	Virginia	United States	22908