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

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
Chronic Lymphocytic Leukemia (CLL); Lymphoma, Non-Hodgkin (NHL); Acute Myeloid Leukemia (AML); Multiple Myeloma (MM)	Drug: CAL-101	Phase 1

Detailed 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	192 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Study Start Date :	June 2008
Actual Primary Completion Date :	December 2011
Actual Study Completion Date :	August 2012

Arms and Interventions

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Arm	Intervention/treatment
Experimental: one arm	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

Outcome Measures

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Primary Outcome Measures :

1. To evaluate the safety of CAL-101 and determine the dose limiting toxicity in patients with hematologic malignancies. [ Time Frame: 28 days ]

Secondary Outcome Measures :

1. To evaluate the pharmacokinetic parameters, pharmacodynamic effects and clinical response rate following CAL-101 treatment in patients with hematologic malignancies. [ Time Frame: 28 Days ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Locations

United States, California
Stanford Cancer Center
Palo Alto, California, United States, 94304-5548
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Weill Medical College of Cornell
New York, New York, United States, 10021
United States, Ohio
The Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239-3098
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792-5156

Sponsors and Collaborators

Gilead Sciences

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kahl BS, Spurgeon SE, Furman RR, Flinn IW, Coutre SE, Brown JR, Benson DM, Byrd JC, Peterman S, Cho Y, Yu A, Godfrey WR, Wagner-Johnston ND. A phase 1 study of the PI3Kδ inhibitor idelalisib in patients with relapsed/refractory mantle cell lymphoma (MCL). Blood. 2014 May 29;123(22):3398-405. doi: 10.1182/blood-2013-11-537555. Epub 2014 Mar 10.

Brown JR, Byrd JC, Coutre SE, Benson DM, Flinn IW, Wagner-Johnston ND, Spurgeon SE, Kahl BS, Bello C, Webb HK, Johnson DM, Peterman S, Li D, Jahn TM, Lannutti BJ, Ulrich RG, Yu AS, Miller LL, Furman RR. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia. Blood. 2014 May 29;123(22):3390-7. doi: 10.1182/blood-2013-11-535047. Epub 2014 Mar 10.

Flinn IW, Kahl BS, Leonard JP, Furman RR, Brown JR, Byrd JC, Wagner-Johnston ND, Coutre SE, Benson DM, Peterman S, Cho Y, Webb HK, Johnson DM, Yu AS, Ulrich RG, Godfrey WR, Miller LL, Spurgeon SE. Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-δ, as therapy for previously treated indolent non-Hodgkin lymphoma. Blood. 2014 May 29;123(22):3406-13. doi: 10.1182/blood-2013-11-538546. Epub 2014 Mar 10.

Stevenson FK, Krysov S, Davies AJ, Steele AJ, Packham G. B-cell receptor signaling in chronic lymphocytic leukemia. Blood. 2011 Oct 20;118(16):4313-20. doi: 10.1182/blood-2011-06-338855. Epub 2011 Aug 3.

Responsible Party:	Langdon Miller, M.D., VP Clinical Research, Onoclogy, Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00710528 History of Changes
Other Study ID Numbers:	101-02
First Posted:	July 4, 2008
Last Update Posted:	August 31, 2012
Last Verified:	August 2012

Keywords provided by Gilead Sciences:

CLL; NHL; AML; MM; Phosphatidylinositol 3-kinase

Additional relevant MeSH terms:

Idelalisib; Leukemia; Leukemia, Myeloid, Acute; Multiple Myeloma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases	Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphatic Diseases; Leukemia, B-Cell; Lymphoma; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action