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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00352742
• Other study ID #: ATN-224-007
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: July 13, 2006
• Last updated: October 27, 2008
• Start date: June 2006
• Est. completion date: December 2008

Study information

• Verified date: October 2008
• Source: Attenuon
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 46
• Est. completion date: December 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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

2. 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

3. 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

4. Age >18 years

5. Life expectancy of greater than 3 months

6. ECOG performance status <2 (Karnofsky >60%; see Appendix A)

7. 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.

8. 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.

9. Willingness to forego taking copper- or zinc-containing vitamins or supplements

10. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. 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

2. Patients who cannot tolerate, based on previous experience, the assigned dose of bortezomib, including those with = Grade 2 neuropathy

3. Concurrent administration of any other investigational agents

4. History of malabsorption syndromes or other gastrointestinal disorders that may affect ATN-224 absorption, including bowel obstruction, celiac disease, sprue, cystic fibrosis

5. Ineligible to receive omeprazole (Prilosec® OTC) or other long-acting antacid

6. Inability to swallow study medication capsules

7. Not a suitable candidate in the opinion of the investigator for additional bortezomib therapy

8. Other serious medical or psychiatric illness preventing informed consent or intensive treatment

9. 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

10. Women who are pregnant or lactating

11. Known history of HIV

12. 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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• ATN-224 + bortezomib
ATN-224 and bortezomib dose to be determined in Phase I portion of study

Locations

Country	Name	City	State
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Billings Clinic	Billings	Montana
United States	SUNY Downstate	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Hematolgy-Oncology Medical Group of Fresno, Inc.	Fresno	California
United States	The Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Tyler Cancer Center	Tyler	Texas
United States	Institute for Myeloma and Bone Cancer Research	West Hollywood	California

Sponsors (1)

Lead Sponsor	Collaborator
Attenuon

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I: Determine a safe dose of ATN-224 and bortezomib to be used in the phase II portion of the study		Ongoing	Yes
Primary	Phase II: Efficacy		End of Study	No
Secondary	Phase I: Preliminary evidence of efficacy		End of Study	No
Secondary	Phase II: progression-free survival and duration of response		End of Study	No