Know Cancer

forgot password

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

Phase 1/Phase 2
18 Years
Not Enrolling
Multiple Myeloma

Thank you

Trial Information

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

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

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.

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)


- 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

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

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

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

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)

Type of Study:


Study Design:

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

Outcome Measure:

Phase I: Determine a safe dose of ATN-224 and bortezomib to be used in the phase II portion of the study

Outcome Time Frame:


Safety Issue:


Principal Investigator

Gilad Gordon, MD

Investigator Role:

Study Director


United States: Food and Drug Administration

Study ID:




Start Date:

June 2006

Completion Date:

December 2008

Related Keywords:

  • Multiple Myeloma
  • Multiple myeloma
  • bortezomib
  • ATN-224
  • refractory
  • relapsed
  • antiangiogenic
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



Roswell Park Cancer Institute Buffalo, New York  14263
Florida Cancer Specialists Fort Myers, Florida  33901
Mary Crowley Medical Research Center Dallas, Texas  75246
Tyler Cancer Center Tyler, Texas  75702
The Cancer Institute of New Jersey New Brunswick, New Jersey  08901
Center for Cancer and Blood Disorders Bethesda, Maryland  20817
Billings Clinic Billings, Montana  59107-7000
Hematolgy-Oncology Medical Group of Fresno, Inc. Fresno, California  93720
Institute for Myeloma and Bone Cancer Research West Hollywood, California  90069
SUNY Downstate Brooklyn, New York  11203