T2012-002: A Pilot Study of Vincristine Sulfate Liposome Injection (Marqibo®) in Combination with Chemotherapy for Children, Adolescents, and Young Adults with Relapse of Acute Lymphoblastic Leukemia (IND 128316)
Study Chair: Nirali N. Shah, MD, MHS– National Cancer Institute, Pediatric Oncology Branch
Vice Chair: Alan S. Wayne, MD – Children’s Hospital Los Angeles
What is this study about:
This study is for patients with relapsed or refractory Acute Lymphoblastic Leukemia (ALL), mixed phenotypic acute leukemia and lymphoblastic lymphoma.
This is a study of a drug called Marqibo® in combination with intensive cytotoxic chemotherapy consisting of mitoxantrone, PEG-asparaginase, and dexamethasone. Methotrexate will also be given to help treat leukemia in the central nervous system. Marqibo® is a new formulation of a type of chemotherapy called vincristine. It is considered experimental because it has not been used in combination with mitoxantrone, PEG-asparaginase and dexamethasone. We are using Marqibo® in this new study because it seems to work against cancer in cells and animals. Marqibo® has been used in only a small number of adults and children and there is a lot that we do not know about it yet.
This is a phase I study. In a phase I study, drugs are tested to the highest dose that can be safely given. Drugs are given at gradually increasing dosages until there are unacceptable side effects. The goal of the Phase I study is to find out the dose of Marqibo® that can be safely given with mitoxantrone, PEG-asparaginase, and dexamethasone to children with relapsed ALL.
Marqibo® will also be studied with less intensive chemotherapy regimens to try to learn how safe Marqibo® is with other chemotherapy combinations.
18 to 39 children and young adults will participate in this study. Another 6 patients can enroll in the Group B higher intensity chemotherapy group, which uses Marqibo ®, PEG-Asparaginase and dexamethasone before the study closes.
Why is this study being done:
The goals of this study are:
· To assess the safety and feasibility of giving Marqibo® with cytotoxic chemotherapy;
· To learn what kind of side effects Marqibo® cause;
· To learn more about the pharmacology (how your body handles the drug) of Marqibo®;
· To determine whether Marqibo®, combined with cytotoxic chemotherapy is a beneficial treatment for relapsed ALL.
Criteria that need to be met to participate in this study: (Abbreviated List)
· Patients must be greater than or equal to 1 year of age and less than or equal to 21 years of age to participate in this study.
· Patients must have relapsed or resistant ALL or lymphoblastic lymphoma with detectable disease, mixed phenotypic acute leukemia and lymphoblastic lymphoma.
· Patients must have adequate kidney, heart and liver function.
Patients cannot participate in the study if: (Abbreviated List)
· They are pregnant or breast-feeding.
· They have disease in the testicles only.
· They have active uncontrolled infection.
· Are taking certain medications that interfere with the drugs used on this study.
Treatment:
If the exams, tests and procedures show that it is safe for you to be enrolled on the study, and you choose to take part, you will be assigned to Group A, Group B or Group C and receive the following drugs as a single course of therapy:
Group A
· Marqibo®: given by intravenous (IV) infusion on days 1, 8, 15 and 22.
· Dexamethasone orally twice daily on days 1-5 and 15-19.
· Mitoxantrone: given by intravenous (IV) infusion on days 1 and 2.
· PEG-asparaginase: given as an injection into the muscle on days 3 and 17.
· Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8.
|
Drug |
Days |
Dose |
|
Marqibo® |
1, 8, 15 and 22 |
As assigned, IV |
|
Dexamethasone |
1-5 and 15-19 |
20 mg/m2/day , oral twice per day |
|
Mitoxantrone |
1 and 2 |
10 mg/m2/day IV |
|
PEG-Asparaginase** |
3 and 17 |
2500 mg/m2 IM or IV |
|
Methotrexate IT |
1 and 8 |
IT dose depends on age |
**Erwinia asparaginase, Erwinia chrysanthemi, asparaginase Erwinia chrysanthemi (recombinant)-rwyn or crisantapase can be substituted for patients only in the setting of allergy to PEG-asparaginase.
Group B
· Marqibo®: given by intravenous (IV) infusion on days 1, 8, 15 and 22.
· Dexamethasone orally twice daily on days 1-5 and 15-19.
· PEG-asparaginase: given as an injection into the muscle on days 3 and 17.
· Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8.
|
Drug |
Days |
Dose |
|
Marqibo® |
1, 8, 15 and 22 |
As assigned, IV |
|
Dexamethasone |
1-5 and 15-19 |
20 mg/m2/day , oral twice per day |
|
PEG-Asparaginase** |
3 and 17 |
2500 mg/m2 IM or IV |
|
Methotrexate IT |
1 and 8 |
IT dose depends on age |
**Erwinia asparaginase, Erwinia chrysanthemi, asparaginase Erwinia chrysanthemi (recombinant)-rwyn or crisantapase can be substituted for patients only in the setting of allergy to PEG-asparaginase.
Group C
· Marqibo®: given by intravenous (IV) infusion on day 1
· Dexamethasone orally twice daily on days 1-5
· Methotrexate: given orally on days 1 and 8
· Mercaptopurine: given orally daily on days 1-13
|
Drug |
Days |
Dose |
|
Marqibo® |
1 |
As assigned, IV |
|
Dexamethasone |
1-5 |
6 mg/m2/day , oral twice per day |
|
Methotrexate |
1 and 8 |
20 mg/m2/day, orally |
|
Mercaptopurine |
1-13 |
75 mg/m2/day, orally |
This course for Group C can be repeated one additional time.
Your bone marrow will be tested at the end of the study treatment to determine if the leukemia cells have reduced in number.
Various methods will be used to give drugs:
· PO – Drug is given by tablet of liquid swallowed through the mouth
· IV – Drug is given using a needle or tubing inserted into a vein; it can be given by IV push over several minutes or by infusion over minutes to hours
· IM – Drug is given using a needle injected into the muscle (IM shot)
· IT – Drug used to treat the brain and spinal cord is given using a needle inserted into the spinal canal
Click here to see a sample of the informed consent for this study which includes additional information about study requirements, treatment and side effects.
Click here to be taken to the T2012-002 Marqibo clinicaltrials.gov web page.
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