Protocol Summary

Protocol No.: OCR16040

Sponsor Protocol No.: AAML1421

Study Title
A Phase 1/2 Study of CPX-351 (NSC# 775341) Alone Followed by Fludarabine, Cytarabine, and G-CSF (FLAG) for Children With Relapsed Acute Myeloid Leukemia (AML) (IND: 129443)

Principal Investigator(s)
Slayton, William

Objective
This phase I/II trial studies the side effects and best dose of liposomal cytarabine-daunorubicin CPX-351 (CPX-351) when given with fludarabine phosphate, cytarabine, and filgrastim and to see how well they work in treating younger patients with acute myeloid leukemia that has come back after treatment (relapsed) or is not responding to treatment (is refractory). Liposomal cytarabine-daunorubicin CPX-351 is made up of two chemotherapy drugs, cytarabine and daunorubicin hydrochloride, and works to stop cancer cell growth by blocking the cells from dividing. Drugs used in chemotherapy, such as fludarabine phosphate and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Filgrastim may increase the production of blood cells and may help the immune system recover from the side effects of chemotherapy. Giving liposomal cytarabine-daunorubicin CPX-351 followed by fludarabine phosphate, cytarabine, and filgrastim may be a better treatment for patients with relapsed acute myeloid leukemia and may cause fewer side effects to the heart, a common effect of other chemotherapy treatments for acute myeloid leukemia.

Description
COURSE 1: Patients receive cytarabine intrathecally (IT) on day 0 and at day 28-30 or up to 1 week prior to day 1 of course 2, and liposomal cytarabine-daunorubicin CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5. Patients without evidence of central nervous system (CNS) disease (CNS1) receive no further CNS-directed therapy in course 1. Patients with COURSE 2: Beginning 28 days later, patients receive filgrastim subcutaneously (SC) on days 1-5 and then on day 15 until blood count recovery, and fludarabine phosphate IV over 30 minutes and high-dose cytarabine IV over 1-3 hours on days 1-5.
After completion of study treatment, patients are followed up periodically for 12 months, and then yearly for 5 years.

Phase: Phase I/II (Cancer Control)

Age Group: Children

Scope: National

Treatment
Treatment (CPX-351 and FLAG)
COURSE 1: Patients receive cytarabine IT on day 0 and at day 28-30 or up to 1 week prior to day 1 of course 2, and liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with CNS1 receive no further CNS-directed therapy in course 1. Patients with CNS2 disease may receive an additional dose of cytarabine IT on day 7 at the discretion of the investigator. Patients meeting criteria for CR, CRp, and CRi may proceed to course 2.
COURSE 2: Beginning 28 days later, patients receive filgrastim SC on days 1-5 and then on day 15 until blood count recovery, and fludarabine phosphate IV over 30 minutes and high-dose cytarabine IV over 1-3 hours on days 1-5.

Detailed Eligibility
INCLUSION CRITERIA:
1. Ages 1 to 21 years old
2. Patients must have had histologic verification of AML at original diagnosis;
3. Patient must have one of the following:
- Recurrent disease with >= 5% blasts in the bone marrow (M2/M3 bone marrow), with or without extramedullary disease
- Recurrent disease with an absolute blast count greater than 1,000 per microliter in the peripheral blood with or without extramedullary disease
4. To be eligible for the dose-finding phase:(The Dose-Finding Phase completed in 12/2016)
- Relapsed patients
- Patients must be in first relapse, and
- Patients must not have received prior re-induction therapy
- Refractory patients
- Patients must not have received more than one attempt at remission induction, which may consist of up to two different therapy courses; Children Oncology Group (COG) AAML1031 de novo therapy including induction I and induction II is an example
- Treatment-related AML (t-AML)
- Patients must be previously untreated for secondary AML
5. To be eligible for the Phase 2 efficacy phase:
- Relapsed patients:
- Patients must be in first marrow relapse, and
- Patients must not have received prior re-induction therapy. Donor lymphocyte infusion (DLI) is considered a re-induction attempt.
6. Patients must have the status of CNS1 or CNS2 only, and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy
7. Patients must have a performance status corresponding to an Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =8. Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, stem cell transplant or radiotherapy prior to entering this study; all prior treatment-related toxicities must have resolved to =9. Myelosuppressive chemotherapy: must not have received myelosuppressive chemotherapy within 3 weeks of entry onto this study (excluding hydroxyurea)
- Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of CPX-351
10. Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent such as steroids, retinoids; Note: for agents that have known adverse events occurring beyond 7 days after administration (i.e. monoclonal antibodies), this period must be extended beyond the time during which acute adverse events are known to occur
11. Radiation therapy (RT): >= 2 weeks for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation; Note: patients must have received =12. Stem cell transplant (SCT): no evidence of active graft vs. host disease for at least 4 weeks; for allogeneic SCT patients, >= 3 months must have elapsed since transplant
- Must have received no more than 1 prior autologous or allogeneic stem cell transplant.
- Patients must be off all systemic immunosuppressive therapy for at least 2 weeks, excluding hydrocortisone for physiologic cortisol replacement
13. Intrathecal cytotoxic therapy:
- No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone
- At least 14 days must have elapsed since receiving liposomal cytarabine (DepoCyte) by intrathecal injection

** Contact study team for complete eligibility details

Applicable Disease Sites
Leukemia
Pediatric (Childhood) Cancer

Participating Institutions
UF Gainesville : Heather Rogers

Contact
Heather Rogers, RN
Phone: +1 352-294-8743

Email: heatherrogers@ufl.edu

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02642965