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A Phase I Study of the Safety and Pharmacokinetics of Escalating Intravenous Doses of the Proteasome Inhibitor PR-171 in Patients With Hematological Malignancies

Phase 1
18 Years
Not Enrolling
Waldenstrom's Macroglobulinemia

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Trial Information

A Phase I Study of the Safety and Pharmacokinetics of Escalating Intravenous Doses of the Proteasome Inhibitor PR-171 in Patients With Hematological Malignancies

Inclusion Criteria:

1. Written informed consent in accordance with federal, local, and institutional

2. Males and females ≥18 years of age

3. Histologically confirmed diagnosis of one of the hematologic malignancies below:

Waldenström's Macroglobulinemia

4. Subjects who are refractory or relapsed following at least two prior therapies

5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 2 (See Appendix 6:
ECOG Performance Status subjects with ECOG of 3 based solely on bone pain may be

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
AST and ALT of <3.0 times the upper limit of normal

8. Total WBC count ≥ 2,000/mm3, ANC ≥ 1000/mm3, hemoglobin ≥8.0 g/dL, and platelet count

- Screening ANC should be independent of G-CSF or 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 (140-Age)X Mass (kg)/(72 X creatinine mg/dL) X 0.85 (if female)

10. Serum creatinine ≤ 2.0 mg/dL

11. Uric acid, if elevated, must be corrected to within laboratory normal range prior to

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-CD20 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

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 HIV infection or who are HIV

14. Active hepatitis A, B, or C infection; or positive for Hep C RNA or hepBsAG

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 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

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

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:

To evaluate the safety and tolerability of carfilzomib (PR-171), including determination of its Dose Limiting Toxicity (DTL) and Maximum Tolerated Dose (MTD).

Outcome Time Frame:

Up to 12 months.

Safety Issue:


Principal Investigator

Mai Le, MD

Investigator Role:

Study Director

Investigator Affiliation:

Onyx Pharmaceuticals


United States: Food and Drug Administration

Study ID:




Start Date:

September 2005

Completion Date:

September 2010

Related Keywords:

  • Waldenstrom's Macroglobulinemia
  • Hematological
  • Proteasome
  • Myeloma
  • Lymphoma
  • Waldenstrom Macroglobulinemia
  • Hematologic Neoplasms



Memorial Sloan Kettering Cancer Center New York, New York  10021
H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612
Tower Cancer Research Foundation Beverly Hills, California  90211
Weil Medical College of Cornell University New York, New York  10021
Herbert Irving Comprehensive Cancer Center, Columbia University New York, New York  10032