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Protocol Details

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

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 2
Max Age: 21

Referral Letter Required


Population Exclusion(s)

Pregnant Women;


Refractory ALL;
M2 Marrow;
M3 Marrow

Recruitment Keyword(s)



ALL, Childhood;
Lymphoblastic Leukemia, Acute, Childhood;
Lymphoblastic Leukemia, Acute

Investigational Drug(s)


Investigational Device(s)



Drug: Marqibo in combination with UK ALL R3

Supporting Site

National Cancer Institute


Most children with acute lymphoblastic leukemia (ALL) can be cured with standard treatment. But about 20 percent have their ALL comes back. Marqibo is a modification of a standard drug (vincristine) given in ALL therapy and was recently FDA approved to to treat ALL in adults. Researchers want to find out if it can be safely given as substation for standard vincristine in combination chemotherapy treatment to children and young adults with relapsed ALL.


To test the side effects and effectiveness of Marqibo with other standard chemotherapy drugs in treating children and young adults with relapsed ALL.


People ages 2-21 with relapsed ALL


Participants will be screened with:

Medical history

Physical exam

Small amount of bone marrow removed by needle into the hipbone

Lumbar puncture. A small amount of spinal fluid is removed by needle in the spine.

Blood, urine, and heart tests

Participants will repeat screening tests during the study.

Participants will get 1 month of treatment:

4 weekly doses of Marqibo by IV

Dexamethasone by mouth on 10

Mitoxantrone through IV on 2 days

Pegaspargase by muscle injection on 2 days. Participants allergic to PEG will get 6 doses of another injection for each dose of PEG.

Methotrexate by lumbar puncture on 2 days. The spinal fluid is removed. Then the drug is injected into the spine.

Participants will have a final visit within 30 days of their last dose of study drugs.

Researchers will collect medical data from participants after the study to see how their ALL is responding.

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1. Age: Patients must be greater than or equal to 1 and less than or equal to 21 years of age at the time of enrollment.


--The NCI plans to enroll patients greater than or equal to 2 years and less than or equal to 21 years.

2. Diagnosis:

-Cohort A: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL, T or B cell) or mixed phenotypic acute leukemia with greater than or equal to 5% blasts in the bone marrow (M2 or M3 by aspirate or flow cytometry), with or without extramedullary disease or a diagnosis of lymphoblastic lymphoma.

-Cohorts B & C: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL, T or B cell), lymphoblastic lymphoma, or mixed phenotypic acute leukemia with any level of detectable disease (minimal residual disease level acceptable) with or without extramedullary disease

3. Performance Level: Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients less than or equal to 16 years of age.

4. Prior Therapy:

a. Patients must have recovered from the acute toxic effects (less than or equal to Grade 2 or baseline) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, unless otherwise specified. Subjects with disease related cytopenias will be eligible.

b. Patients must have relapsed or refractory disease.

c. Patients with Philadelphia chromosome t(9;22) positive disease must have received at least two prior tyrosine kinase inhibitors.

d. Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of graft-versus-host disease (GVHD) and are at least 100 days post-transplant at the time of enrollment ; and at least 30 days off any systemic immunosuppression.

e. Prior anthracycline lifetime cumulative exposure:

-Cohort A: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy.

-Cohorts B & C: There is no limit on prior anthracycline exposure.

f. Hematopoietic growth factors: It must have been at least seven days since the completion of therapy with GCSF or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta ).

g. Biologic anti-neoplastic agents: At least seven days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond seven days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair or vice chair.

h. Monoclonal antibodies: At least three half-lives (or 30 days whichever is longer) of the antibody must have elapsed after the last dose of monoclonal antibody. (e.g., Rituximab = 66 days, Epratuzumab = 69 days)

i. Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines, chimeric antigen receptor T-cells.

j. Recent prior chemotherapy: At least 10 days after standard vincristine and the completion of any type of chemotherapy induction regimen. At least 3 weeks after radiation therapy. At least 30 days after the completion of any investigational neoplastic agent is also required. An investigational agent is defined as any drug that is not approved and licensed for sale by the FDA for institutions in the United States, by Health Canada for institutions in Canada and by The Therapeutic Goods Administration for institutions in Australia.


- There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such; it is allowable to enroll a patient that has received IT ARA-C, IT MTX or triple IT therapy within 14 days of enrollment as part of their evaluation to diagnose disease relapse. The IT therapy given within 14 days of initiation of protocol specified chemotherapy, may substitute for the day 1 IT n cohorts A and B.

- Subjects with rapidly progressive disease may receive hydroxyurea until they begin study therapy;

- Patients who relapse while on maintenance-type ALL therapy or are receiving maintenance therapy for disease stabilization will not require a wash-out period before entry into this study. However, there must be at least 10 days after any dose of standard vincristine.

-For radiation therapy: Radiation therapy must have been completed at least 3 weeks prior to enrollment (including CNS radiation), with the exception that there is no time restriction if the volume of bone marrow treated is less than 10% and also the subject has measurable/evaluable disease outside the radiation port.

5. Renal and Hepatic Function

a. Renal function: Patient s serum creatinine must be less than or equal to 1.5 x institutional upper limit of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times normal, the patient must have a calculated creatinine clearance or radioisotope GFR greater than or equal to 70mL/min/1.73m(2). Alternatively, a 24-hour creatinine clearance may also be used.

- Pediatric Population (age <18): Calculated creatinine clearance greater than or equal to 70 ml/min/1.73m(2) as calculated by the Schwartz formula for estimated glomerular filtration rate (GFR) where GFR (ml/min/1.73 m(2)) = k*Height (cm)/serum creatinine (mg/dl). k is a proportionality constant which varies with age and is a function of urinary creatinine excretion per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70

adolescent boys.

- Adult Population (age greater than or equal to18): If serum creatinine 1.5 X ULN, then the estimated glomerular filtration rate (GFR) must be 70 mL/min/1.73 m(2) as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m(2) = 186 x (Serum Creatinine) (-1.154) x (age in years)(-0.023) x (0.742 if patient is female) x (1.212 if patient is black.

b. Hepatic function: ALT and AST must be < 3 x institutional upper limit of norm ULN. Total bilirubin must be less than or equal to 1.5 x ULN (except in the case of subjects with documented Gilbert s disease less than or equal to 5 (SqrRoot) ULN).

6. Cardiac Function: Patients must have a shortening fraction greater than or equal to 27% or an ejection fraction greater than or equal to 55% by echocardiogram, cardiac MRI or MUGA.

7. Reproductive Function:

a. Female patients must not be pregnant and those of childbearing potential must have a negative urine or serum pregnancy test confirmed within one week prior to enrollment.

b. Female patients with infants must agree not to breastfeed their infants while on this study.

c. Male and female patients of childbearing potential must agree to use an effective method of contraception during the study.


- Patients will be excluded if they haveany isolated extramedullary disease, including isolated testicular or isolated CNS disease.

- Patients will be excluded if they have previously received Marqibo .

- Patients will be excluded if they have a known allergy to any of the drugs used in the study, with the exception that patients with an allergy to pegaspargase who can receive Erwinia asparaginase are eligible. Patients unable to receive any formulation of asparaginase may only enroll on cohort C.

- Patients will be excluded if they have active, uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment.

- Patients who require azole antifungal agents will be excluded. Azoles must be discontinued at least one week prior to the start of Marqibo .

- Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, another investigational agent or immunotherapy during the study period.

- Patients with pre-existing, persistent grade 2 or greater sensory or motor neuropathy from any cause will be excluded. (Patients on chronic stable doses of gabapentin or similar agents for history of neuropathy may be included if there are no active neuropathic symptoms)

- Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or adherence with the protocol treatment or procedures or interfere with consent, study participation, follow up, or interpretation of study results.

a. Patients with Down syndrome will not be eligible for enrollment on Cohort A

- Patients with a known history human immunodeficiency virus (HIV) will be excluded due to the increased risk of complications such as severe infection and unknown interaction of Marqibo with antiretroviral drugs.

- Active hepatitis B or C infection as defined by seropositive for hepatitis B (hepatitis B surface antigen (HBsAg)) or hepatitis C and elevated liver transaminases (defined as above the ULN per the institution normal ranges).

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Nirali N. Shah, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 1-5750
(240) 760-6970

NCI Pediatric Leukemia, Lymphoma Transpl
National Cancer Institute (NCI)

(240) 760-6970

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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