Phase I Trial to Evaluate the Safety, Activity and Pharmacokinetics of Marqibo(Registered Trademark) (Vincristine Sulfate Liposomes Injection) in Children and Adolescents With Refractory Cancer
- INCLUSION CRITERIA
AGE: Subjects must be greater than or equal to 2 years and < 21 years of age.
DIAGNOSIS: Histologically confirmed solid tumors, which may include but are not limited to
rhabdomyosarcoma and other soft tissue sarcomas, Ewing sarcoma family of tumors,
osteosarcoma, neuroblastoma, Wilms tumor, hepatic tumors, germ cell tumors, and primary
brain tumors. In subjects with brain stem or optic gliomas the requirement for
histological confirmation may be waived.
-Histologically confirmed diagnosis of hematologic malignancy, including but not limited
to acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), Hodgkin's
lymphoma, and non-Hodgkin's lymphoma (NHL). Isolated CNS or testicular disease is NOT
MEASURABLE/EVALUABLE DISEASE: Subjects must have measurable or evaluable malignant
- The subject s cancer must have relapsed after or failed to respond to frontline
curative therapy and there must not be other potentially curative treatment options
available to that subject at the time of study entry.
- Subjects must have had their last doses of therapy prior to receiving the first dose
of the investigational agent as follows (provided there is complete recovery from any
acute toxic effects of such):
1. Chemotherapy at least 14 days (6 weeks for nitrosoureas);
2. Radiation at least 21 days;
3. Any investigational cancer therapy or monoclonal antibody therapy (e.g.,
rituximab) at least 30 days.
Exceptions to these requirements:
- Intrathecal chemotherapy: There is no time restriction in regard to prior intrathecal
chemotherapy provided there is complete recovery from any acute toxic effects of
- Radiation therapy: There is no time restriction in regard to prior radiation provided
the volume of bone marrow treated is less than 10% and that there is measurable
disease outside the radiation port.
- Patients receiving corticosteroids or hydroxyurea are eligible provided all of the
following conditions are met.
- Patients with CNS tumors who are managed with steroids are eligible if they are on a
stable or decreasing dose of steroids and have no worsening neurologic deficits for
greater than or equal to 7 days prior to registration.
- The subject is not on both corticosteroids and hydroxyurea
- Corticosteroids are not being used to manage GVHD.
- There has been no increase in the hydroxyurea dose for 2 weeks prior to starting
- Subjects must have recovered from the toxic effects (Grade 1 or baseline) of all
prior therapy before entry onto this trial.
- Subjects should be off hematopoietic colony stimulating factors for at least 72 hours
prior to study entry.
- Subjects with prior history of stem cell transplantation must be off
immunosuppressive therapy for at least 4 weeks and have no active graft-versus-host
disease (GVHD) with the exception of Grade 1 acute at the time of entry onto this
PERFORMANCE STATUS: Subjects have a performance level greater than or equal to 50.
HEPATIC FUNCTION: Subjects must have adequate liver function, defined as bilirubin < 2.0
times the upper limit of normal, SGPT (ALT) and SGOT (AST) < 2.5 times the upper limit of
RENAL FUNCTION: Subjects must have an age-adjusted normal serum creatinine OR a creatinine
clearance greater than or equal to 60 mL/min/1.73 m(2):
- For age less than or equal to 5 - Maximum Serum Creatinine: 0.8
- For age less than 5 or less than or equal to 10 - Maximum Serum Creatinine: 1.0
- For age less than 10 or less than or equal to 15 - Maximum Serum Creatinine: 1.2
- For age greater than 15 - Maximum Serum Creatinine: 1.5
INFORMED CONSENT/ASSENT: All subjects or their legal guardians (for subjects < 18 years of
age) must sign a document of informed consent (POB eligibility screening protocol) prior
to performing studies to determine subject eligibility. After confirmation of subject
eligibility all subjects or their legal guardians must sign the protocol-specific informed
consent to document their understanding of the investigational nature and the risks of
this study before any protocol related studies are performed (other than the studies that
were performed to determine subject eligibility). Where deemed appropriate by the
clinician and the child s parents or guardian, the child will also be included in all
discussions about the trial and verbal assent will be obtained. The parent or guardian
will sign the designated line on the informed consent attesting to the fact that the child
has given assent.
DURABLE POWER OF ATTORNEY (DPA): Subjects who have brain tumors and who are 18 years of
age will be offered the opportunity to assign a DPA so that another person can make
decisions about their medical care if they become incapacitated or cognitively impaired.
BIRTH CONTROL: Subjects of childbearing or child-fathering potential must be willing to
use a medically acceptable form of birth control, which includes abstinence, while they
are being treated on this study. Females of childbearing potential must have a negative
pregnancy test within 7 days prior to starting study drug.
ADDITIONAL INCLUSION CRITERIA FOR EXPANDED COHORT OF ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
DIAGNOSIS: Subjects must have a diagnosis of relapsed or refractory ALL or lymphoblastic
lymphoma with > 5% marrow blasts (M2 or M3). Isolated CNS or testicular disease is not
allowed. If < 5% marrow blasts must have histologically confirmed leukemia in
Clinically significant unrelated systemic illness, such as uncontrolled serious infection
or organ dysfunction, which in the judgment of protocol investigators would compromise the
subject s ability to tolerate the investigational agent or interfere with the study
procedures or results. This includes any condition or circumstance that in the opinion of
the investigator would significantly interfere with the subject s protocol compliance and
put the subject at increased risk.
CNS leukemia or lymphoma as manifested by any of the following:
- CSF WBC > 5/microL and confirmation of CSF blasts.
- Cranial neuropathies deemed secondary to underlying malignancy
- CT or MRI scan evidence.
* Note: History of CNS involvement is not an exclusion criterion.
- Neutrophil count < 1,000/microL or platelet count of < 50,000/microL (except for the
expanded ALL cohort, where there is no blood count requirement).
- Pregnant or breast-feeding females are excluded because Marqibo(Registered Trademark)
may be harmful to the developing fetus or nursing child.
- Currently receiving other investigational agents.
- History of previously receiving Marqibo(Registered Trademark).
- History of allergic reactions or serious adverse events attributed to compounds of
similar chemical or biologic composition to vincristine or components of
Marqibo(Registered Trademark) (vincristine sulfate injection,
sphingomyelin/cholesterol liposomes, sodium phosphate injection).
- Are eligible for stem cell transplantation. This implies that a suitable donor is
readily available, that the primary oncology team and Principal Investigator
recommend this as a preferred treatment option at the time of protocol evaluation,
and that the subject is willing to undergo stem cell transplantation.
- Presence of preexisting Grade 2 or greater sensory or motor neuropathy.
- History of persistent greater than or equal to Grade 2 active neurologic disorders
unrelated to chemotherapy.
- Positive for human immunodeficiency virus (HIV) due to the increased risk of