A Study of ATN-224 and Bortezomib in Patients With Multiple Myeloma

Sponsor

Attenuon (Industry)

Overall Status

Terminated

CT.gov ID

NCT00352742

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

4.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to describe the safety and effect of ATN-224 in combination with bortezomib (Velcade®) in patients with Multiple Myeloma who are relapsed from or refractory to bortezomib.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: ATN-224 + bortezomib	Phase 1/Phase 2

Detailed Description

Multiple myeloma is a bone marrow based malignancy of plasma cells that is highly treatable but rarely curable. Angiogenesis, defined as the growth of new blood vessels from pre-existing vessels, is a requirement for the growth of nearly all tumors. An increase in bone marrow angiogenesis is present in Multiple Myeloma and correlates with disease progression. Several new therapies that target angiogenic pathways have shown clinical efficacy. ATN-224 is a small molecule that has been shown in pre-clinical studies to be antiangiogenic.

Using one agent to overcome resistance of another agent is a treatment regimen used in oncology. A preclinical study with the combination of ATN-224 and bortezomib shows that the combination is more effective than either single agent in a bortezomib resistant cell line.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

46 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II Study of ATN-224 and Bortezomib in Patients With Multiple Myeloma Relapsed From or Refractory to Bortezomib

Study Start Date :

Jun 1, 2006

Anticipated Primary Completion Date :

Sep 1, 2008

Anticipated Study Completion Date :

Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 ATN-224 + bortezomib	Drug: ATN-224 + bortezomib ATN-224 and bortezomib dose to be determined in Phase I portion of study

Arm

Intervention/Treatment

Experimental: 1

ATN-224 + bortezomib

Drug: ATN-224 + bortezomib

ATN-224 and bortezomib dose to be determined in Phase I portion of study

Outcome Measures

Primary Outcome Measures

Phase I: Determine a safe dose of ATN-224 and bortezomib to be used in the phase II portion of the study [Ongoing]
Phase II: Efficacy [End of Study]

Secondary Outcome Measures

Phase I: Preliminary evidence of efficacy [End of Study]
Phase II: progression-free survival and duration of response [End of Study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed multiple myeloma that has been treated with at least one different prior anti-myeloma regimens including one with bortezomib and is currently showing evidence of progressive disease
Myeloma that is refractory to the most recent bortezomib-containing regimen as demonstrated by progressive disease while on bortezomib or that relapsed within 12 weeks of the last dose of bortezomib either as a single agent or in combination with other agents
Measurable disease defined as a serum M-protein concentration on electrophoresis ≥1 g/dL of IgG myeloma or ≥0.5 g/dL of IgA myeloma or IgM myeloma or urinary excretion of monoclonal light chain ≥200 mg/24 hours
Age >18 years
Life expectancy of greater than 3 months
ECOG performance status <2 (Karnofsky >60%; see Appendix A)
Adequate organ and marrow function as defined below:

absolute neutrophil count ≥1,000/uL
platelets ≥75,000/uL
hemoglobin ≥8 g/dL
total bilirubin ≤2 X institutional upper limit of normal (ULN)
AST(SGOT) and ALT(SGPT) ≤3 X ULN
creatinine clearance ≥30 mL/min (measured or calculated)

Patients are allowed to receive blood transfusions before receiving their first dose of ATN-224 to bring the hemoglobin level to ≥8 g/dL to meet eligibility criteria.

Use of adequate contraception. The effects of ATN 224 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because antiangiogenic agents are known to be teratogenic, women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal and/or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation through the follow up visit 28 days after the last dose of ATN 224.
Willingness to forego taking copper- or zinc-containing vitamins or supplements
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or thalidomide, lenalidomide, dexamethasone, arsenic trioxide, bortezomib, or glucocorticosteroids within 3 weeks prior to the first dose of ATN-224 or failure to recover from reversible adverse events due to agents administered previously
Patients who cannot tolerate, based on previous experience, the assigned dose of bortezomib, including those with ≥ Grade 2 neuropathy
Concurrent administration of any other investigational agents
History of malabsorption syndromes or other gastrointestinal disorders that may affect ATN-224 absorption, including bowel obstruction, celiac disease, sprue, cystic fibrosis
Ineligible to receive omeprazole (Prilosec® OTC) or other long-acting antacid
Inability to swallow study medication capsules
Not a suitable candidate in the opinion of the investigator for additional bortezomib therapy
Other serious medical or psychiatric illness preventing informed consent or intensive treatment
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Women who are pregnant or lactating
Known history of HIV
History of another prior cancer, except basal cell carcinoma or carcinoma in situ of the cervix (or if there has been no evidence of recurrence for at least 5 years)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hematolgy-Oncology Medical Group of Fresno, Inc.	Fresno	California	United States	93720
2	Institute for Myeloma and Bone Cancer Research	West Hollywood	California	United States	90069
3	Florida Cancer Specialists	Fort Myers	Florida	United States	33901
4	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
5	Billings Clinic	Billings	Montana	United States	59101
6	The Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
7	SUNY Downstate	Brooklyn	New York	United States	11203
8	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
9	Mary Crowley Medical Research Center	Dallas	Texas	United States	75246
10	Tyler Cancer Center	Tyler	Texas	United States	75702