Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapsed ALL
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| ClinicalTrials.gov Identifier: NCT02879643 |
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Recruitment Status : Unknown
Verified April 2020 by Therapeutic Advances in Childhood Leukemia Consortium.
Recruitment status was: Recruiting
First Posted : August 26, 2016
Last Update Posted : April 17, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| ALL, Childhood Lymphoblastic Leukemia, Acute, Childhood Lymphoblastic Leukemia, Acute | Drug: Marqibo | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 36 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Pilot Study of Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapse of Acute Lymphoblastic Leukemia |
| Actual Study Start Date : | January 31, 2017 |
| Estimated Primary Completion Date : | August 31, 2021 |
| Estimated Study Completion Date : | December 31, 2022 |
| Arm | Intervention/treatment |
|---|---|
Experimental: Cohort A: Marqibo and UK ALL R3 backbone
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Drug: Marqibo
The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts. |
Experimental: Cohort B: Marqibo and lower intensity UK ALL R3 backbone
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Drug: Marqibo
The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts. |
Experimental: Cohort C: Marqibo and maintenance regimen
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Drug: Marqibo
The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts. |
- Number of Participants with Dose Limiting Toxicities as a Measure of Safety and Tolerability [ Time Frame: 5 weeks ]The incidence of dose limiting toxicity (DLT) will be measured at different dose levels.
- The response rate after treatment. [ Time Frame: Approx. 8 weeks ]The rate of remission will be assessed after 1 courses of therapy. A bone marrow aspirate/biopsy and CBC will be conducted to assess response.
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| Ages Eligible for Study: | 1 Year to 21 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria
Age
-Patients must be ≥ 1 and ≤ 21 years of age at the time of enrollment.
Diagnosis
- Cohort A: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) or mixed phenotypic acute leukemia with ≥ 5% blasts in the bone marrow (M2 or M3), with or without extramedullary disease) or a diagnosis of lymphoblastic lymphoma.
- Cohorts B & C: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma, or mixed phenotypic acute leukemia with any level of detectable disease (minimal residual disease level acceptable) with or without extramedullary disease
Performance Level -Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age.
Prior Therapy
- Patients must have recovered from the acute toxic effects (≤ 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.
- Patients must have relapsed or refractory disease after attaining at least a first remission. They may be in first to third relapse..
- Patients with Philadelphia chromosome t(9;22) positive disease must have received at least two prior tyrosine kinase inhibitors.
- Patients who have experienced their relapse after a Hematopoietic stem cell transplantation (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.
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Prior anthracycline lifetime cumulative exposure: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy.
- Cohort A: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy (See Appendix 2 for anthracycline calculation worksheet).
- Cohorts B & C: There is no limit on prior anthracycline exposure.
- Hematopoietic growth factors: It must have been at least seven days since the completion of therapy with granulocyte colony-stimulating factor (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®).
- 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.
- 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)
- Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines, chimeric antigen receptor T-cells.
- 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.
Exceptions:
- 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 Cytarabine (ARA-C), IT Methotrexate (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 in 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.
Renal and Hepatic Function
- Renal function: Patient's serum creatinine must be ≤ 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 glomerular filtration rate (GFR) ≥ 70milliliter/min/1.73m2. Alternatively, a 24-hour creatinine clearance may also be used.
- Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be < 5 x institutional upper limit of norm ULN. Total bilirubin must be ≤ 1.5 x ULN (except in the case of subjects with documented Gilbert's disease ≤ 5 × ULN).
Cardiac Function
-Patients must have a shortening fraction ≥ 27% or an ejection fraction ≥ 55% by echocardiogram, cardiac MRI or multigated acquisition scan (MUGA).
Reproductive Function
- 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.
- Female patients with infants must agree not to breastfeed their infants while on this study.
- Male and female patients of childbearing potential must agree to use an effective method of contraception during the study.
Exclusion Criteria
Patients will be excluded if they have isolated testicular 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 PEG-asparaginase 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 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.Patients with Down syndrome will not be eligible for enrollment on Cohort A
Patients with a known history of human immunodeficiency virus (HIV) will 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02879643
| Contact: Ellynore Florendo | (323) 361- 3022 | eflorendo@chla.usc.edu | |
| Contact: Lei-Lani Miller | (323) 361-5429 | llmiller@chla.usc.edu |
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| Responsible Party: | Therapeutic Advances in Childhood Leukemia Consortium |
| ClinicalTrials.gov Identifier: | NCT02879643 |
| Other Study ID Numbers: |
T2012-002 |
| First Posted: | August 26, 2016 Key Record Dates |
| Last Update Posted: | April 17, 2020 |
| Last Verified: | April 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Acute Disease Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Disease Attributes Pathologic Processes Vincristine Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action |