Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors

PRIMARY OBJECTIVES:

I. To determine the objective response rate, defined as partial response or better, of
imetelstat (imetelstat sodium) in children with relapsed or refractory solid tumors.

II. To further define and describe the toxicities associated with imetelstat in children
with recurrent/refractory solid tumors.

SECONDARY OBJECTIVES:

I. To determine the time to progression following treatment with imetelstat in children with
relapsed or refractory solid tumors.

TERTIARY OBJECTIVES:

I. To measure tumor telomere length in archival samples, and to correlate telomere length to
the clinical outcome of the study.

OUTLINE:

Patients receive imetelstat sodium intravenously (IV) over 2 hours on days 1 and 8.
Treatment repeats every 21 days for up to 36 courses in the absence of disease progression
or unacceptable toxicity.

Inclusion Criteria:

- Patients with any of the following tumors who have relapsed or refractory disease are
eligible:

- Osteosarcoma

- Ewing's sarcoma / peripheral primitive neuroectodermal tumor (PNET)

- Rhabdomyosarcoma

- Neuroblastoma (measurable or evaluable disease)

- Hepatoblastoma

- Patients must have had histologic verification of malignancy at original diagnosis or
relapse

- Patients must have radiographically measurable disease (with the exception of
neuroblastoma)

- Measurable disease is defined as the presence of at least one lesion on magnetic
resonance imaging (MRI) or computed tomography (CT) scan that can be accurately
measured with the longest diameter a minimum of 10 mm in at least one dimension
(CT scan slice thickness no greater than 5 mm)

- Note: the following do not qualify as measurable disease:

- Malignant fluid collections (e.g., ascites, pleural effusions)

- Bone marrow infiltration

- Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as defined below for
neuroblastoma

- Elevated tumor markers in plasma or cerebrospinal fluid (CSF)

- Previously radiated lesions that have not demonstrated clear progression
post radiation

- Leptomeningeal lesions that do not meet the measurements noted above

- Patients with neuroblastoma who do not have measurable disease but have evaluable
disease on 131I-metaiodobenzylguanidine (MIBG) scans are eligible

- Patients must have a Lansky or Karnofsky performance status score of >= 50,
corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use
Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age;
patients who are unable to walk because of paralysis, but who are up in a wheelchair,
will be considered ambulatory for the purpose of assessing the performance score

- Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study

- Myelosuppressive chemotherapy: patients with solid tumors must not have received
myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks
if prior nitrosourea)

- Hematopoietic growth factors: at least 7 days must have elapsed since the completion
of therapy with a growth factor; at least 14 days must have elapsed after receiving
pegfilgrastim

- Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion
of therapy with a biologic agent; for agents that have known adverse events occurring
beyond 7 days after administration, this period prior to enrollment must be extended
beyond the time during which adverse events are known to occur

- Monoclonal antibodies: at least 3 half-lives must have elapsed since prior therapy
that included a monoclonal antibody

- Radiotherapy: >= 2 weeks must have elapsed since local palliative radiation therapy
(XRT) (small port); >= 6 weeks must have elapsed since treatment with therapeutic
doses of MIBG; >= 3 months must have elapsed if prior craniospinal XRT was received,
if >= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was
received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation
was given

- Stem cell transplant or rescue without TBI: no evidence of active graft versus (vs.)
host disease and >= 2 months must have elapsed since transplant

- For patients with solid tumors without bone marrow involvement:

- Peripheral absolute neutrophil count (ANC) >= 1000/uL

- For patients with solid tumors without bone marrow involvement:

- Platelet count >= 100,000/uL (transfusion independent, defined as not receiving
platelet transfusions within a 7 day period prior to enrollment)

- For patients with solid tumors without bone marrow involvement:

- Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions).

- For patients with solid tumors and known bone marrow metastatic disease:

- Peripheral absolute neutrophil count (ANC) >= 750/uL

- For patients with solid tumors and known bone marrow metastatic disease:

- Platelet count >= 50,000/uL

- For patients with solid tumors and known bone marrow metastatic disease:

- Hemoglobin >= 8.0 g/dL

- Transfusions are permitted to meet both the platelet and hemoglobin
criteria; patients must not be known to be refractory to red blood cell or
platelet transfusions

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/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)

- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110
U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)

- Serum albumin >= 2 g/dL

- Activated partial thromboplastin time (aPTT) =< 1.2 x upper limit of normal

Exclusion Criteria:

- Patients who are pregnant or breast-feeding are not eligible for this study; negative
pregnancy tests must be obtained in girls who are post-menarchal; males or females of
reproductive potential may not participate unless they have agreed to use an
effective contraceptive method for the duration of study therapy; study drug may also
potentially be secreted in milk and therefore breastfeeding women are excluded

- Growth factors that support platelet or white cell number or function must not have
been administered within the 7 days prior to enrollment (14 days if pegfilgrastim)

- Patients requiring corticosteroids who have not been on a stable or decreasing dose
of corticosteroid for the 7 days prior to enrollment are not eligible

- Patients who are currently receiving another investigational drug are not eligible

- Patients who are currently receiving other anti-cancer agents are not eligible

- Anti-graft-versus-host disease (GVHD) or agents to prevent organ rejection
post-transplant:

patients who are receiving cyclosporine, tacrolimus or other agents to prevent either
graft-versus-host disease post bone marrow transplant or organ rejection post-transplant
are not eligible for this trial

- Patients who have an uncontrolled infection are not eligible

- Patients who have received prior treatment with imetelstat are not eligible

- Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible

- Patients with prior allogeneic transplants are not eligible