Dose Escalation Study of CAL-101 in Select Relapsed or Refractory Hematologic Malignancies

Acute Myeloid Leukemia (AML) Clinical Trial

Official title:

A Phase 1 Sequential Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of CAL-101 in Patients With Select, Relapsed or Refractory Hematologic Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00710528
• Other study ID #: 101-02
• Status: Completed
• Phase: Phase 1
• First received: July 1, 2008
• Last updated: August 29, 2012
• Start date: June 2008
• Est. completion date: August 2012

Study information

• Verified date: August 2012
• Source: Gilead Sciences
• 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 determine the dose that can be safely given to see what effect it may have on your cancer and to determine how the drug is distributed in the body.

Description:

A Phase 1, sequential dose escalation followed by cohort expansion study of CAL-101, an oral inhibitor of PI3K delta, in patients with relapsed or refractory CLL, select B-cell NHL and AML.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 192
• Est. completion date: August 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age > or = 18.

2. Has relapsed or refractory disease as defined by the following:

• CLL - refractory to or relapsed after at least 2 prior therapies, including fludarabine, alone or in combination. Patients should not be eligible for transplantation (patients who are candidates for transplantation and have declined transplantation are eligible for this study).

• B-cell NHL - refractory to or relapsed after at least 1 prior chemotherapy regimen and having received rituximab as a single agent or in combination with other therapies.

• AML - refractory to or relapsed after at least 1 cycle of induction chemotherapy. Patients over the age of 70 who are not appropriate candidates for chemotherapy are eligible for this study.

• MM - refractory to or relapsed after at least 2 prior chemotherapy regimens, including bortezomib and thalidomide or lenalidomide (except if the drug is contraindicated in a patient then this requirement is waived).

3. Disease status requirement:

• For CLL patients, symptomatic disease that mandate treatment.

• For B-cell NHL patients, has measurable disease by CT scan.

• For AML patients, has > 10% blasts in the bone marrow for refractory or relapsed disease and > 20% blasts in the bone marrow if no prior chemotherapy.

• For MM patients, has measurable disease defined by at least 1 of the following 3 measurements: serum M-protein > or = to 1 g/dL, urine M-protein > or = to 200 mg/24 h, or serum free light chain (FLC) assay with involved FLC level > or = to 10 mg/dL provided serum FLC ratio is abnormal.

4. WHO performance status of = 2.

5. For men and women of child-bearing potential, willing to use adequate contraception (i.e., latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study.

6. Is able to provide written informed consent.

Exclusion Criteria:

1. Had radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 4-weeks prior to screening.

2. For CLL or NHL patients, had treatment with a short course of corticosteroids for symptom relief within 1-week prior to screening.

3. Had alemtuzumab therapy within 12-weeks prior to screening.

4. For AML patients, had treatment with hydroxyurea within 1-week prior to screening.

5. Is pregnant or nursing.

6. Has significant, ongoing co-morbid conditions which would preclude safe delivery of the study drug.

7. Has had a transplant with current active graft-versus-host-disease.

8. Has known active central nervous system involvement of the malignancy.

9. Has active, serious infection requiring systemic therapy. Patients may receive prophylactic antibiotics and antiviral therapy at the discretion of the treating physician.

10. Has significant renal or liver dysfunction.

11. Has severe thrombocytopenia requiring platelet transfusion support, unless the diagnosis is AML.

12. Has a positive test for human immunodeficiency virus (HIV) antibodies.

13. Has active hepatitis B or C. Patients with serologic evidence of prior exposure are eligible.

14. Has poorly controlled diabetes mellitus.

15. Has taken a medication that is a potent inhibitor or inducer of cytochrome P450 3A4 within 1-week prior to screening.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Chronic Lymphocytic Leukemia (CLL)
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myeloid, Acute
• Lymphoma, Non-Hodgkin
• Lymphoma, Non-Hodgkin (NHL)
• Multiple Myeloma
• Multiple Myeloma (MM)
• Neoplasms, Plasma Cell

Intervention

Drug:
• CAL-101
CAL-101 50, 100, 150, 200, 350 mg capsules BID for 28 days CAL-101 150, 300 mg QD for 28 days CAL-101 150 mg BID 3 weeks on 1 week off for 28 days

Locations

Country	Name	City	State
United States	The Sidney Kimmel Comprehensive Cancer Center at John Hopkins	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	University of Wisconsin	Madison	Wisconsin
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Weill Medical College of Cornell	New York	New York
United States	Stanford Cancer Center	Palo Alto	California
United States	Oregon Health and Science University	Portland	Oregon
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the safety of CAL-101 and determine the dose limiting toxicity in patients with hematologic malignancies.		28 days	Yes
Secondary	To evaluate the pharmacokinetic parameters, pharmacodynamic effects and clinical response rate following CAL-101 treatment in patients with hematologic malignancies.		28 Days	No