A Trial of GS-9219 in Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM)
Primary Purpose
Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, Multiple Myeloma
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GS-9219
Sponsored by
About this trial
This is an interventional treatment trial for Non-Hodgkin's Lymphoma focused on measuring Hematologic Malignancies, CLL, NHL, Chronic Lymphocytic Leukemia, Non-Hodgkin's Lymphoma, CLL and NHL, Multiple Myeloma, MM
Eligibility Criteria
Inclusion Criteria:
- Relapsed or refractory CLL, NHL or MM
- ECOG Performance Status of 0, 1, or 2
- Adequate organ function (protocol defined)
- ECG without evidence of clinically significant ventricular arrhythmias
Exclusion Criteria:
- AIDS-related lymphoma
- Subjects with NHL who present exclusively with non-measurable lesions
- Subjects with MM who have non-secretory and/or non-measurable disease
- Recent anticancer therapy (chemotherapy, radiotherapy, and/or biotherapy)within four weeks prior to starting treatment
- Evidence of pulmonary fibrosis
- Other concurrent malignancy
- Uncontrolled concurrent illness
- Receiving chronic, systemically administered steroids
- Known hypersensitivity to nucleoside analogues
Sites / Locations
- UCSF
- Northwestern University
- Dana Farber Cancer Institute
- Nevada Cancer Institute
- MD Anderson Cancer Center
- Fakultni nemocnice Brno - Bohunice
- Fakultni nemocnice Hradec Kralove
- Fakultni nemocnice Olomouc
- Fakultni nemocnice Kralovske Vinohrady
- Vseobecna fakultni nemocnice
- State Institution: Medical Radiological Research Center under the Russian Academy of Medical Sciences
- State institution Main Military Clinical Hospital n.a.academician N.N. Burdenko under the Ministry of Defense of Russia
- State Institution Hematological Research Center under the Russian Academy of Medical Sciences
- Moscow State Medical Institution: Municipal Clinical Hospital n.a. S.P. Botkin
- Non-State Medical Institution Central Clinical Hospital #2 n.a. N.A. Semashko under OJSC "Russian Railways"
- State Public Medical Institution of Novosibirsk Region: State Novosibirsk Regional Clinical Hospital
- Federal State Institution: Research Institute of Hematology and Blood Transfusion under Federal Agency for High-Tech Medical Care
- State Higher Educational Institution St. Petersburg State Medical University n.a. I.P. Pavlov under the Federal Agency for Healthcare and Social Development, Institute of Hematology and Transplantology n.a. R.M. Gorbacheva
- State Higher Educational Institution St. Petersburg State Medical University n.a. I.P. Pavlov under the Federal Agency for Healthcare and Social Development
- Federal State Institution Russian Research Center of Radiology and Surgical Technologies under the Federal Agency for High-Tech Medical Care
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GS-9219
Arm Description
Escalating doses of GS-9219 (5, 8, 11.5, 16, 22.5, 31.5, 44, and 61.5 mg/m^2) until determination of the maximum tolerated dose (MTD)
Outcomes
Primary Outcome Measures
Determination of MTD
Toxicity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE). The MTD will be the highest dose level immediately below the dose level where two or more of three to six patients experience a dose-limiting toxicity (DLT).
Secondary Outcome Measures
Pharmacokinetics of GS-9219 and its metabolites
Pharmacokinetics (Cmax, Tmax, Clast, Tlast, λz, t1/2, AUClast, AUCinf, and %AUCexp) measured by blood sampling
Response rate
Response rate measured by:
CLL: National Cancer Institute Working Group (NCIWG) criteria
NHL - National Cancer Institute (NCI) criteria; Response Evaluation in
MM - International Myeloma Working Group (IMWG) criteria.
Duration of response
Duration of response measured by:
CLL: National Cancer Institute Working Group (NCIWG) criteria
NHL - National Cancer Institute (NCI) criteria; Response Evaluation in
MM - International Myeloma Working Group (IMWG) criteria.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00499239
Brief Title
A Trial of GS-9219 in Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM)
Official Title
Multi-center, Open-label, Dose-escalating Phase I/II Trial of GS-9219 Administered Once Every Three Weeks Intravenously to Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin's Lymphoma or Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Terminated
Why Stopped
Unacceptable safety profile
Study Start Date
July 2007 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
October 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Multi-center, open-label, single-dose, dose-escalating Phase I/II study of GS 9219 in adult patients with relapsed or refractory CLL, NHL or MM. Patients will be enrolled into the study in sequential dose cohorts.
Patients will be administered a single IV infusion of GS 9219 on Day 1 of a 21 day cycle and may receive a total of six treatment cycles based on toxicities and response. Patients who demonstrate disease progression will be discontinued from the study. Patients who, at the completion of six treatment cycles, tolerate treatment and show evidence of disease control (response or stabilization) will be eligible to continue receiving treatment at the same dose.
Detailed Description
The primary objective of this study is as follows:
To assess the safety, toxicity, and maximum tolerated dose (MTD) of GS 9219 administered via IV administration once every three weeks (21 days) for six treatment cycles, i.e. for a total of 18 weeks, in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM).
The secondary objectives of this study are as follows:
To determine the pharmacokinetic parameters of GS 9219 for this regimen and patient population.
To assess the antitumor activity of GS 9219 based on Response Rate and Duration of Response. Progression-free Survival and Overall Survival will be assessed if applicable.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, Multiple Myeloma
Keywords
Hematologic Malignancies, CLL, NHL, Chronic Lymphocytic Leukemia, Non-Hodgkin's Lymphoma, CLL and NHL, Multiple Myeloma, MM
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GS-9219
Arm Type
Experimental
Arm Description
Escalating doses of GS-9219 (5, 8, 11.5, 16, 22.5, 31.5, 44, and 61.5 mg/m^2) until determination of the maximum tolerated dose (MTD)
Intervention Type
Drug
Intervention Name(s)
GS-9219
Intervention Description
GS-9219 Injection is a clear, and colorless to slightly yellow aqueous solution containing 4 mg/mL of GS 9219.
GS 9219 will be administered via IV infusion over 30 minutes in 100 mL of normal saline solution, every 21 days.
Primary Outcome Measure Information:
Title
Determination of MTD
Description
Toxicity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE). The MTD will be the highest dose level immediately below the dose level where two or more of three to six patients experience a dose-limiting toxicity (DLT).
Time Frame
All visits
Secondary Outcome Measure Information:
Title
Pharmacokinetics of GS-9219 and its metabolites
Description
Pharmacokinetics (Cmax, Tmax, Clast, Tlast, λz, t1/2, AUClast, AUCinf, and %AUCexp) measured by blood sampling
Time Frame
AAA) CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6
Title
Response rate
Description
Response rate measured by:
CLL: National Cancer Institute Working Group (NCIWG) criteria
NHL - National Cancer Institute (NCI) criteria; Response Evaluation in
MM - International Myeloma Working Group (IMWG) criteria.
Time Frame
CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6
Title
Duration of response
Description
Duration of response measured by:
CLL: National Cancer Institute Working Group (NCIWG) criteria
NHL - National Cancer Institute (NCI) criteria; Response Evaluation in
MM - International Myeloma Working Group (IMWG) criteria.
Time Frame
CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Relapsed or refractory CLL, NHL or MM
ECOG Performance Status of 0, 1, or 2
Adequate organ function (protocol defined)
ECG without evidence of clinically significant ventricular arrhythmias
Exclusion Criteria:
AIDS-related lymphoma
Subjects with NHL who present exclusively with non-measurable lesions
Subjects with MM who have non-secretory and/or non-measurable disease
Recent anticancer therapy (chemotherapy, radiotherapy, and/or biotherapy)within four weeks prior to starting treatment
Evidence of pulmonary fibrosis
Other concurrent malignancy
Uncontrolled concurrent illness
Receiving chronic, systemically administered steroids
Known hypersensitivity to nucleoside analogues
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Hawkins, MD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Nevada Cancer Institute
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89135
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77303
Country
United States
Facility Name
Fakultni nemocnice Brno - Bohunice
City
Brno
ZIP/Postal Code
625 00
Country
Czech Republic
Facility Name
Fakultni nemocnice Hradec Kralove
City
Hradec Kralove
ZIP/Postal Code
500
Country
Czech Republic
Facility Name
Fakultni nemocnice Olomouc
City
Olomouc
ZIP/Postal Code
775 20
Country
Czech Republic
Facility Name
Fakultni nemocnice Kralovske Vinohrady
City
Praha
ZIP/Postal Code
10 100 34
Country
Czech Republic
Facility Name
Vseobecna fakultni nemocnice
City
Praha
ZIP/Postal Code
2 128 08
Country
Czech Republic
Facility Name
State Institution: Medical Radiological Research Center under the Russian Academy of Medical Sciences
City
Kaluga Region
ZIP/Postal Code
249036
Country
Russian Federation
Facility Name
State institution Main Military Clinical Hospital n.a.academician N.N. Burdenko under the Ministry of Defense of Russia
City
Moscow
ZIP/Postal Code
105229
Country
Russian Federation
Facility Name
State Institution Hematological Research Center under the Russian Academy of Medical Sciences
City
Moscow
ZIP/Postal Code
125167
Country
Russian Federation
Facility Name
Moscow State Medical Institution: Municipal Clinical Hospital n.a. S.P. Botkin
City
Moscow
ZIP/Postal Code
125284
Country
Russian Federation
Facility Name
Non-State Medical Institution Central Clinical Hospital #2 n.a. N.A. Semashko under OJSC "Russian Railways"
City
Moscow
ZIP/Postal Code
129128
Country
Russian Federation
Facility Name
State Public Medical Institution of Novosibirsk Region: State Novosibirsk Regional Clinical Hospital
City
Novosibirsk
ZIP/Postal Code
630087
Country
Russian Federation
Facility Name
Federal State Institution: Research Institute of Hematology and Blood Transfusion under Federal Agency for High-Tech Medical Care
City
St Petersburg
ZIP/Postal Code
191024
Country
Russian Federation
Facility Name
State Higher Educational Institution St. Petersburg State Medical University n.a. I.P. Pavlov under the Federal Agency for Healthcare and Social Development, Institute of Hematology and Transplantology n.a. R.M. Gorbacheva
City
St. Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
State Higher Educational Institution St. Petersburg State Medical University n.a. I.P. Pavlov under the Federal Agency for Healthcare and Social Development
City
St. Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
Federal State Institution Russian Research Center of Radiology and Surgical Technologies under the Federal Agency for High-Tech Medical Care
City
St. Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
12. IPD Sharing Statement
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A Trial of GS-9219 in Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM)
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