Brief Title
Safety Study of the Proteasome Inhibitor PR-171 (Carfilzomib for Injection) in Patients With Hematological Malignancies
Official Title
A Phase I Study of the Safety and Pharmacokinetics of Escalating Intravenous Doses of the Proteasome Inhibitor PR-171 in Patients With Hematological Malignancies
Brief Summary
The purpose of this study is to test the safety and tolerability of carfilzomib at different
dose levels on hematological cancers such as multiple myeloma, non-Hodgkin's lymphoma,
Hodgkin's disease, or Waldenstrom's macroglobulinemia. Carfilzomib is a proteasome inhibitor,
an enzyme responsible for degrading a wide variety of cellular proteins.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Number of Participants With Dose-limiting Toxicities (DLTs)
Secondary Outcome
Best Clinical Response to Treatment
Condition
Waldenstrom's Macroglobulinemia
Intervention
Carfilzomib
Study Arms / Comparison Groups
CFZ 1.2 mg/m²
Description: Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
48
Start Date
September 2005
Completion Date
October 2009
Primary Completion Date
October 2009
Eligibility Criteria
Inclusion Criteria:
1. Written informed consent in accordance with federal, local, and institutional
guidelines
2. Males and females ≥18 years of age
3. Histologically confirmed diagnosis of one of the hematologic malignancies below:
- Multiple myeloma (MM)
- Non-Hodgkin's lymphoma (NHL)
- Waldenström's Macroglobulinemia (WM)
- Hodgkin's disease (HD)
4. Subjects who are refractory or relapsed following at least two prior therapies
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
6. Adequate cardiovascular function without symptomatic ischemia, conduction
abnormalities uncontrolled by conventional intervention, or myocardial infarction in
the previous six months
7. Adequate hepatic function, with bilirubin < 2.0 times the upper limit of normal, and
aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of < 3.0 times the
upper limit of normal
8. Total white blood cell (WBC) count ≥ 2,000/mm³, absolute neutrophil count (ANC) ≥
1000/mm³, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 50,000/mm³
- Screening ANC should be independent of granulocyte colony stimulating factor
(G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) support for
≥ 1 week and of pegylated G-CSF for ≥ 2 weeks)
- Subjects receiving supportive care including erythropoietin, darbepoetin and/or
bisphosphonates can continue to do so, but must be transfusion independent;
subjects receiving erythropoietic support must remain on the same dose for the
first 28 days of study participation
9. An estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of
Cockroft and Gault
10. Serum creatinine ≤ 2.0 mg/dL
11. Uric acid, if elevated, must be corrected to within laboratory normal range prior to
dosing
12. Female subjects of child-bearing potential must agree to use dual methods of
contraception and have a negative serum pregnancy test. Male subjects must use an
effective barrier method of contraception throughout the study and for three months
following the last dose if sexually active with a female of child-bearing potential.
Exclusion Criteria:
1. Female subjects who are pregnant or lactating
2. Subjects who are transfusion dependent
3. Subjects with NHL or HL who have received steroid therapy in the previous seven days
4. Subjects with MM or Waldenström's Macroglobulinemia who have received steroid therapy
in the previous three weeks, except for MM subjects in the Carfilzomib + DEX Expansion
Cohort, where previous treatment with dexamethasone will be allowed. The dose and
schedule of administration of dexamethasone will be adjusted to that used in the
protocol
5. Radiation, chemotherapy, or immunotherapy in the previous four weeks, or subjects who,
in the judgment of the Investigator, have not recovered from the effects of previous
therapy
6. For the Dose Escalation period, subjects who have received prior radioimmunotherapy
with anti-cluster of differentiation (CD)20 monoclonal antibodies such as Bexxar® or
Zevalin®; subjects treated with these products will be allowed in the Dose Expansion
period
7. Subjects who have received allogeneic stem cell transplant therapy
8. Subjects with NHL or HL who have received autologous stem cell transplant therapy and
have relapsed within 100 days of therapy
9. Rituxan therapy within three months before Day 1 unless there is evidence of disease
progression
10. Major surgery within three weeks before Day 1
11. Congestive heart failure (CHF) (New York Heart Association class III to IV)
12. Acute active infection requiring systemic antibiotics, antivirals, or antifungals
within two weeks prior to first dose
13. Subjects who are known or suspected of having human immunodeficiency virus (HIV)
infection or who are HIV seropositive
14. Active hepatitis A, B, or C infection; or positive for Hepatitis C ribonucleic acid
(RNA) or hepatitis B antigen
15. Non-hematologic malignancy within the past three years except a) adequately treated
basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c)
prostate cancer with stable prostate specific antigen (PSA) levels for three years
16. Subjects with treatment-related myelodysplastic disorder
17. Subjects with known brain metastasis (active central nervous system [CNS] disease
only)
18. Serious psychiatric or medical conditions that could interfere with treatment
19. Participation in an investigational therapeutic study within one month prior to Day 1
20. Significant neurotoxicity (Grade 2 or higher with pain) at the time of study
initiation
21. Concurrent therapy with approved or investigative anticancer therapeutics
22. Subjects with previous hypersensitivity to bortezomib injection
23. Subjects with contraindications to receiving allopurinol
24. Subjects in whom the required program of oral and intravenous fluid hydration is
contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment
25. Subjects with known or suspected amyloidosis
26. Subjects with pleural effusions requiring thoracentesis or ascites requiring
paracentesis
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00150462
Organization ID
PX-171-002
Responsible Party
Sponsor
Study Sponsor
Amgen
Study Sponsor
MD, Study Director, Amgen
Verification Date
April 2017