Imetelstat Sodium in Treating Young Patients With Refractory or Recurrent Solid Tumors or Lymphoma

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT01273090

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

1.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Imetelstat sodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I clinical trial is studying the side effects and best dose of imetelstat sodium in treating young patients with refractory or recurrent solid tumors or lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors Lymphoma Lymphoproliferative Disorder Small Intestine Cancer Unspecified Childhood Solid Tumor, Protocol Specific	Drug: imetelstat sodium Other: laboratory biomarker analysis Other: pharmacological study	Phase 1

Detailed Description

OBJECTIVES:

Primary

To estimate the maximum-tolerated dose (MTD) and/or recommended phase II dose of imetelstat sodium in children with refractory or recurrent solid tumors or lymphoma.
To define and describe the toxicities of imetelstat sodium.
To characterize the pharmacokinetics of imetelstat sodium in children with refractory or recurrent solid tumors or lymphoma.

Secondary

To determine, in a preliminary manner, the antitumor effects of imetelstat sodium in children with refractory or recurrent solid tumors or lymphoma. (exploratory)
To provide preliminary assessment of the biological activity of imetelstat sodium in children with recurrent or refractory malignancies by assessing telomerase activity, telomere length, hTERT protein, hTERT mRNA, and hTR levels in patient peripheral blood mononuclear cells (PBMNC) samples pretreatment and on treatment. (Exploratory)
To assess telomerase activity, hTERT expression, telomere length, hTERT protein, hTERT mRNA, and hTR levels in patients' pretreatment tumor samples. (Exploratory)

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive imetelstat sodium IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection at baseline and periodically during study for pharmacokinetic and correlative studies. Tumor tissue samples from diagnosis and/or subsequent tumor resections or biopsies may also be collected for correlative studies.

After completion of study therapy, patients are followed up for 30 days.

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study of Imetelstat, a Telomerase Inhibitor, in Children With Refractory or Recurrent Solid Tumors and Lymphomas

Study Start Date :

May 1, 2011

Actual Primary Completion Date :

Sep 1, 2013

Actual Study Completion Date :

Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment	Drug: imetelstat sodium Other: laboratory biomarker analysis Other: pharmacological study

Arm

Intervention/Treatment

Experimental: Treatment

Drug: imetelstat sodium

Other: laboratory biomarker analysis

Other: pharmacological study

Outcome Measures

Primary Outcome Measures

Maximum-tolerated dose and/or recommended phase II dose of imetelstat sodium in children with refractory or recurrent solid tumors or lymphoma [21 Days]
Toxicities of imetelstat sodium [Up to 30 days post-treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of refractory or recurrent solid tumors, including lymphoma
No CNS tumors or known CNS metastases (Part A, dose escalation)
CNS tumors or known CNS metastases allowed (Part B, maximum-tolerated dose or recommended phase II dose)
No prior or concurrent CNS hemorrhage on a baseline MRI within the past 14 days
All patients must have histologic verification of malignancy at original diagnosis or relapse except for:
Intrinsic brain stem tumors
Optic pathway gliomas
Pineal tumors and elevations of CSF or serum tumor markers including alpha-fetoprotein or beta-HCG
Measurable or evaluable disease
Disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood count criteria and they are not known to be refractory to red cell or platelet transfusions

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 50-100% (patients > 16 years of age) OR Lansky PS 50-100% (patients ≤ 16 years of age)
ANC ≥ 1,000/mm³
Platelet count ≥ 100,000/mm³ (transfusion-independent, defined as not receiving platelet transfusion within the past 7 days prior to enrollment)
Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR a serum creatinine based on age and/or gender as follows:
0.6 mg/dL (1 to < 2 years of age)
0.8 mg/dL (2 to < 6 years of age)
1.0 mg/dL (6 to < 10 years of age)
1.2 mg/dL (10 to < 13 years of age)
1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
Bilirubin (sum of conjugated and unconjugated) ≤ 1.5 times upper limit of normal (ULN)
ALT ≤ 110 U/L (ULN for ALT is 45 U/L)
Serum albumin ≥ 2 g/dL
aPTT < 1.2 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use an effective contraception method
No uncontrolled infection
No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

PRIOR CONCURRENT THERAPY:

Recovered from acute toxic effects of all prior anti-cancer chemotherapy, immunotherapy, or radiotherapy
At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)
At least 14 days since prior long-acting growth factor (e.g., Neulasta) or ≥ 7 days since prior short-acting growth factor
At least 7 days since prior biologic or anti-neoplastic agent
At least 6 weeks since any type of prior immunotherapy (e.g., tumor vaccines)
At least 3 half-lives since last dose of a monoclonal antibody
At least 2 weeks since prior local palliative radiotherapy (small port)
At least 24 weeks since prior total-body irradiation, craniospinal radiotherapy, or radiation to ≥ 50% of the pelvis
At least 6 weeks since prior substantial bone marrow radiation
At least 12 weeks since prior transplantation or stem cell infusion with no evidence of active graft vs host disease
Prior and concurrent stable or decreasing dose of corticosteroids within the past 7 days allowed
No prior allogeneic transplant
No other concurrent investigational drug
No other concurrent anticancer agents including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
No concurrent cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease post-bone marrow transplant or organ rejection post-transplant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Comprehensive Cancer Center	Birmingham	Alabama	United States	35294
2	Children's Hospital of Orange County	Orange	California	United States	92868
3	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
4	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
5	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus	Atlanta	Georgia	United States	30322
6	Children's Memorial Hospital - Chicago	Chicago	Illinois	United States	60611
7	Riley's Children Cancer Center at Riley Hospital for Children	Indianapolis	Indiana	United States	46202
8	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland	United States	20892-1182
9	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute	Boston	Massachusetts	United States	2115
10	C.S. Mott Children's Hospital at University of Michigan Medical Center	Ann Arbor	Michigan	United States	48109-0286
11	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	St. Louis	Missouri	United States	63110
12	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York	United States	10032
13	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
14	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon	United States	97239-3098
15	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
16	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15213
17	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
18	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
19	Baylor University Medical Center - Houston	Houston	Texas	United States	77030-2399
20	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
21	Midwest Children's Cancer Center at Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
22	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
23	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5