A Trial of GS-9219 in Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM)

Sponsor

Gilead Sciences (Industry)

Overall Status

Terminated

CT.gov ID

NCT00499239

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma Chronic Lymphocytic Leukemia Multiple Myeloma	Drug: GS-9219	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jul 1, 2007

Actual Primary Completion Date :

Jul 1, 2010

Actual Study Completion Date :

Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GS-9219 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)	Drug: GS-9219 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.

Arm

Intervention/Treatment

Experimental: GS-9219

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)

Drug: GS-9219

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.

Outcome Measures

Primary Outcome Measures

Determination of MTD [All visits]
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 [AAA) CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6]
Pharmacokinetics (Cmax, Tmax, Clast, Tlast, λz, t1/2, AUClast, AUCinf, and %AUCexp) measured by blood sampling
Response rate [CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6]
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 [CLL/NHL: at Cycles 1, 3, and 6: MM: Cycles 1, 2, 3, 4, 5, and 6]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF	San Francisco	California	United States	94143
2	Northwestern University	Chicago	Illinois	United States	60611
3	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	Nevada Cancer Institute	Las Vegas	Nevada	United States	89135
5	MD Anderson Cancer Center	Houston	Texas	United States	77303
6	Fakultni nemocnice Brno - Bohunice	Brno		Czech Republic	625 00
7	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czech Republic	500
8	Fakultni nemocnice Olomouc	Olomouc		Czech Republic	775 20
9	Fakultni nemocnice Kralovske Vinohrady	Praha		Czech Republic	10 100 34
10	Vseobecna fakultni nemocnice	Praha		Czech Republic	2 128 08
11	State Institution: Medical Radiological Research Center under the Russian Academy of Medical Sciences	Kaluga Region		Russian Federation	249036
12	State institution Main Military Clinical Hospital n.a.academician N.N. Burdenko under the Ministry of Defense of Russia	Moscow		Russian Federation	105229
13	State Institution Hematological Research Center under the Russian Academy of Medical Sciences	Moscow		Russian Federation	125167
14	Moscow State Medical Institution: Municipal Clinical Hospital n.a. S.P. Botkin	Moscow		Russian Federation	125284
15	Non-State Medical Institution Central Clinical Hospital #2 n.a. N.A. Semashko under OJSC "Russian Railways"	Moscow		Russian Federation	129128
16	State Public Medical Institution of Novosibirsk Region: State Novosibirsk Regional Clinical Hospital	Novosibirsk		Russian Federation	630087
17	Federal State Institution: Research Institute of Hematology and Blood Transfusion under Federal Agency for High-Tech Medical Care	St Petersburg		Russian Federation	191024
18	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	St. Petersburg		Russian Federation	197022
19	State Higher Educational Institution St. Petersburg State Medical University n.a. I.P. Pavlov under the Federal Agency for Healthcare and Social Development	St. Petersburg		Russian Federation	197022
20	Federal State Institution Russian Research Center of Radiology and Surgical Technologies under the Federal Agency for High-Tech Medical Care	St. Petersburg		Russian Federation	197758