AC220 for Children With Relapsed/Refractory ALL or AML

• Sponsor: Therapeutic Advances in Childhood Leukemia Consortium (Other)
• Overall Status: Completed
• CT.gov ID: NCT01411267
• Collaborator: Ambit Biosciences Corporation (Industry)
• Enrollment: 24
• Locations: 11
• Arms: 10
• Actual Duration (Months): 24.4
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a phase I study of the investigational drug AC220 combined with cytarabine and etoposide in pediatric patients with relapsed acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML).

Condition or Disease	Intervention/Treatment	Phase
Lymphoblastic Leukemia, Acute, Childhood; Myelogenous Leukemia, Acute, Childhood	Drug: AC220; Drug: Cytarabine; Drug: Etoposide; Drug: Methotrexate	Phase 1

Detailed Description

This is a study for pediatric patients with relapsed acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). Some people diagnosed with leukemia have changes in a receptor located on the surface of white blood cells called FLT3. This is known as a FLT3 mutation. FLT3 plays an important role in the way cells grow and divide. In normal cells, the FLT3 receptor is switched off most of the time and only switches on when it gets a chemical signal from outside. But cells with the FLT3 mutation have the grow signal permanently switched on. This means leukemia cells with the FLT3 mutation are growing and dividing all the time. Doctors have found that people with leukemia cells that carry FLT3 mutations are less likely to go into remission with chemotherapy and have a higher risk of the leukemia coming back after treatment.

This is a study of an investigational drug called AC220. AC220 is considered investigational because it has not been approved in the United States by the Food and Drug Administration (FDA). AC220 is a drug which is able to "turn off" the FLT3 grow signal. AC220 will be given with cytarabine and etoposide to treat the relapsed leukemia. This is a phase I study, which means that the study is being done to find the highest dose of AC220 that can be given safely with the drugs cytarabine and etoposide to children and young adults.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study of AC220 for Children With Relapsed or Refractory ALL or AML
• Actual Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Sep 12, 2013
• Actual Study Completion Date: Sep 12, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALL AC220 @ 25mg/m2/day (Dose Level 1) The starting dose is Dose Level 1 at 25 mg/m2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age.	Drug: AC220; Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.; Other Names: Quizartinib ; Drug: Cytarabine; All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day "1" of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age; Other Names: Cytosine Arabinoside Ara-C Cytosar®-U Arabinosylcytosine ; Drug: Etoposide; 150 mg/m2/day IV on days 1 through 5.; Other Names: VePesid® Etopophos VP-16 Toposar® Etoposide phosphate ; Drug: Methotrexate; IT methotrexate given intrathecally to patients with ALL on day "0" of course 1 and 2. Dose defined by age 6 mg for patients age < 1yr 8 mg for patients age 1-1.99 10 mg for patients age 2-2.99 12 mg for patients 3-8.99 years of age 15 mg for patients >9 years of age; Other Names: MTX Amethopterin Otrexup™ Rasuvo® Rheumatrex® Trexall™ Methotrexate Sodium
Experimental: AML AC220 @ 25mg/m2/day (Dose Level 1) The starting dose is Dose Level 1 at 25 mg/m2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age.	Drug: AC220; Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.; Other Names: Quizartinib ; Drug: Cytarabine; All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day "1" of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age; Other Names: Cytosine Arabinoside Ara-C Cytosar®-U Arabinosylcytosine ; Drug: Etoposide; 150 mg/m2/day IV on days 1 through 5.; Other Names: VePesid® Etopophos VP-16 Toposar® Etoposide phosphate
Experimental: ALL AC220 @ 40mg/m2/day (Dose Level 2) Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age.	Drug: AC220; Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.; Other Names: Quizartinib ; Drug: Cytarabine; All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day "1" of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age; Other Names: Cytosine Arabinoside Ara-C Cytosar®-U Arabinosylcytosine ; Drug: Etoposide; 150 mg/m2/day IV on days 1 through 5.; Other Names: VePesid® Etopophos VP-16 Toposar® Etoposide phosphate ; Drug: Methotrexate; IT methotrexate given intrathecally to patients with ALL on day "0" of course 1 and 2. Dose defined by age 6 mg for patients age < 1yr 8 mg for patients age 1-1.99 10 mg for patients age 2-2.99 12 mg for patients 3-8.99 years of age 15 mg for patients >9 years of age; Other Names: MTX Amethopterin Otrexup™ Rasuvo® Rheumatrex® Trexall™ Methotrexate Sodium
Experimental: ALL AC220 @ 60mg/m2/day (Dose Level 3) Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.	Drug: AC220; Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.; Other Names: Quizartinib ; Drug: Cytarabine; All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day "1" of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age; Other Names: Cytosine Arabinoside Ara-C Cytosar®-U Arabinosylcytosine ; Drug: Etoposide; 150 mg/m2/day IV on days 1 through 5.; Other Names: VePesid® Etopophos VP-16 Toposar® Etoposide phosphate ; Drug: Methotrexate; IT methotrexate given intrathecally to patients with ALL on day "0" of course 1 and 2. Dose defined by age 6 mg for patients age < 1yr 8 mg for patients age 1-1.99 10 mg for patients age 2-2.99 12 mg for patients 3-8.99 years of age 15 mg for patients >9 years of age; Other Names: MTX Amethopterin Otrexup™ Rasuvo® Rheumatrex® Trexall™ Methotrexate Sodium
Experimental: ALL AC220 @ 90mg/m2/day (Dose Level 4) If the study dose of 60 mg/m2/day at Dose Level 3 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 4 at 90 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 4 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.	Drug: AC220; Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.; Other Names: Quizartinib ; Drug: Cytarabine; All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day "1" of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age; Other Names: Cytosine Arabinoside Ara-C Cytosar®-U Arabinosylcytosine ; Drug: Etoposide; 150 mg/m2/day IV on days 1 through 5.; Other Names: VePesid® Etopophos VP-16 Toposar® Etoposide phosphate ; Drug: Methotrexate; IT methotrexate given intrathecally to patients with ALL on day "0" of course 1 and 2. Dose defined by age 6 mg for patients age < 1yr 8 mg for patients age 1-1.99 10 mg for patients age 2-2.99 12 mg for patients 3-8.99 years of age 15 mg for patients >9 years of age; Other Names: MTX Amethopterin Otrexup™ Rasuvo® Rheumatrex® Trexall™ Methotrexate Sodium
Experimental: ALL AC220 @ 130 mg/m2/day (Dose Level 5) If the study dose of 90 mg/m2/day at Dose Level 4 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 5 at 130 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. Dose Level 5 is the highest dose for this study.	Drug: AC220; Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.; Other Names: Quizartinib ; Drug: Cytarabine; All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day "1" of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age; Other Names: Cytosine Arabinoside Ara-C Cytosar®-U Arabinosylcytosine ; Drug: Etoposide; 150 mg/m2/day IV on days 1 through 5.; Other Names: VePesid® Etopophos VP-16 Toposar® Etoposide phosphate ; Drug: Methotrexate; IT methotrexate given intrathecally to patients with ALL on day "0" of course 1 and 2. Dose defined by age 6 mg for patients age < 1yr 8 mg for patients age 1-1.99 10 mg for patients age 2-2.99 12 mg for patients 3-8.99 years of age 15 mg for patients >9 years of age; Other Names: MTX Amethopterin Otrexup™ Rasuvo® Rheumatrex® Trexall™ Methotrexate Sodium
Experimental: AML AC220 @ 40mg/m2/day (Dose Level 2) Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age.	Drug: AC220; Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.; Other Names: Quizartinib ; Drug: Cytarabine; All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day "1" of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age; Other Names: Cytosine Arabinoside Ara-C Cytosar®-U Arabinosylcytosine ; Drug: Etoposide; 150 mg/m2/day IV on days 1 through 5.; Other Names: VePesid® Etopophos VP-16 Toposar® Etoposide phosphate
Experimental: AML AC220 @ 60mg/m2/day (Dose Level 3) Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.	Drug: AC220; Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.; Other Names: Quizartinib ; Drug: Cytarabine; All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day "1" of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age; Other Names: Cytosine Arabinoside Ara-C Cytosar®-U Arabinosylcytosine ; Drug: Etoposide; 150 mg/m2/day IV on days 1 through 5.; Other Names: VePesid® Etopophos VP-16 Toposar® Etoposide phosphate
Experimental: AML AC220 @ 90mg/m2/day (Dose Level 4) If the study dose of 60 mg/m2/day at Dose Level 3 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 4 at 90 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 4 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.	Drug: AC220; Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.; Other Names: Quizartinib ; Drug: Cytarabine; All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day "1" of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age; Other Names: Cytosine Arabinoside Ara-C Cytosar®-U Arabinosylcytosine ; Drug: Etoposide; 150 mg/m2/day IV on days 1 through 5.; Other Names: VePesid® Etopophos VP-16 Toposar® Etoposide phosphate
Experimental: AML AC220 @ 130mg/m2/day (Dose Level 5) If the study dose of 90 mg/m2/day at Dose Level 4 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 5 at 130 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. Dose Level 5 is the highest dose for this study.	Drug: AC220; Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.; Other Names: Quizartinib ; Drug: Cytarabine; All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day "1" of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age; Other Names: Cytosine Arabinoside Ara-C Cytosar®-U Arabinosylcytosine ; Drug: Etoposide; 150 mg/m2/day IV on days 1 through 5.; Other Names: VePesid® Etopophos VP-16 Toposar® Etoposide phosphate

Outcome Measures

Primary Outcome Measures

1. The Dose of AC220 That is Safe and Biologically Active When Given in Sequential Combination With Ara-C/Etoposide [4 weeks from therapy start]

   The incidence of dose limiting toxicity (DLT) will be measured. The maximum tolerated dose will be the highest study dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy. Plasma inhibitor activity (PIA) will be measured Pre-treatment and on Days 7, 14, 21 and 28 of Course 1. For the MTD to be considered biologically active, we will require that 7 of 9 patients achieve PIA of > 90% at 3 of 4 trough time points.

Secondary Outcome Measures

1. Disease Response [10 weeks]

   Possible outcomes are: Complete Remission (CR), Complete Remission without Platelet Recovery (CRp), complete response with incomplete hematologic recovery (CRi), Stable Disease, Progressive Disease, Induction Death, or Relapse

2. Count of Participants According to Inhibition of FLT3 Phosphorylation [4 weeks from therapy start]

   PIA samples will be collected pre-treatment and on Days 7, 14, 21 and 28 of Course 1.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Month to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must be greater than 1 month and ≤ 21 years of age at study entry.

• Patients must have a diagnosis of relapsed/refractory AML, ALL or acute leukemia of ambiguous lineage and meet the following criteria:

1. Patients with AML or leukemia with ambiguous lineage must have greater than or equal to 5% blasts in the bone marrow.

2. Patients with ALL must have an M3 marrow (marrow blasts >25%).

3. Patients with ALL must have MLL gene rearrangement or hyperdiploid >50 chromosomes.

4. Patients with treatment related AML (t-AML) are eligible, provided they meet all other eligibility criteria.

• Karnofsky > 50% for patients >16 years of age and Lansky >50% for patients ≤16 years of age.

• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

• Myelosuppressive chemotherapy:

• Patients with ALL who relapse during standard maintenance therapy are eligible at time of relapse.

• For patients with ALL and AML who relapse while they are receiving cytotoxic therapy, at least 14 days must have elapsed since the completion of cytotoxic therapy.

• Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of AC220.

• Patients who have received other FLT3 inhibitors (ex. lestaurtinib, sorafenib) are eligible for this study.

• Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor.

• Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 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.

• XRT: 2 wks must have elapsed since local palliative XRT for CNS chloromas; No washout period is necessary for other chloromas; at least 3 months must have elapsed if prior TBI, craniospinal XRT.

• Hematopoetic Stem Cell Transplant: At least 90 days must have elapsed since hematopoietic stem cell transplant (HSCT) and patients must not have active GVHD.

• Patient must have adequate renal and hepatic functions as indicated by the following laboratory values:

• Patients must have a calculated creatinine clearance or radioisotope GFR ≥70mL/min/1.73m2 or a normal serum creatinine based on age/gender.

• Total bilirubin <1.5 x ULN for age or normal conjugated bilirubin.

• Alanine transaminase (ALT) <5 × ULN (unless related to leukemic involvement).

• Patient must have a shortening fraction of ≥ 27% by echocardiogram, OR an ejection fraction of ≥ 50% by radionuclide angiogram.

• Reproductive Function

• Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment.

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

• Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment.

Exclusion Criteria:

• Patients will be excluded if they have CNS 3 disease.

• Patients will be excluded if they have uncontrolled or significant cardiovascular disease, including:

• A myocardial infarction within 12 months.

• Uncontrolled angina within 6 months.

• Diagnosed or suspected congenital long QT syndrome or any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes [TdP]); any history of arrhythmia will be discussed with the Sponsor's Medical Monitor prior to patient's entry into the study.

• Prolonged QTcF interval on pre-entry ECG (≥450 ms).

• Any history of second or third degree heart block (may be eligible if the patient currently has a pacemaker).

• Heart rate < 50/minute on pre-entry ECG.

• Uncontrolled hypertension.

• Complete left bundle branch block.

• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or TdP.

• Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours.

• Patient is receiving or plans to receive concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.

• Any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.

• Patients who are concurrently receiving CYP3A4 and 5 inhibitors and inducers

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital Los Angeles	Los Angeles	California	United States	90027
2	Children's Hospital Central California	Madera	California	United States	93636
3	UCSF School of Medicine	San Francisco	California	United States	94143-0106
4	The Children's Hospital, University of Colorado	Aurora	Colorado	United States	80045
5	Children's Healthcare of Atlanta, Emory University	Atlanta	Georgia	United States	30322
6	Johns Hopkins University	Baltimore	Maryland	United States	21231
7	Dana Farber	Boston	Massachusetts	United States	02215
8	Children's Mercy Hospitals and Clinics	Kansas City	Missouri	United States	64108
9	Levine Children's Hospital at Carolinas Medical Center	Charlotte	North Carolina	United States	28203
10	Oregon Health and Science University	Portland	Oregon	United States	97239
11	Seattle Children's Hospital	Seattle	Washington	United States	98105

Sponsors and Collaborators

• Therapeutic Advances in Childhood Leukemia Consortium
• Ambit Biosciences Corporation

Investigators

• Study Chair: Todd Cooper, MD, Children's Healthcare of Atlanta, Emory University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Therapeutic Advances in Childhood Leukemia & Lymphoma Consortium web site

Publications

None provided.

• Responsible Party: Therapeutic Advances in Childhood Leukemia Consortium
• ClinicalTrials.gov Identifier: NCT01411267
• Other Study ID Numbers: T2009-004
• First Posted: Aug 8, 2011
• Last Update Posted: Apr 4, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Therapeutic Advances in Childhood Leukemia Consortium: Relapse; Lymphoblastic; Leukemia; AC220; Refractory; Myelogenous; Acute; Childhood; Pediatric; ALL; AML
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Acute Disease; Cytarabine; Methotrexate; Etoposide; Etoposide phosphate

Study Results

Participant Flow

Arm/Group Title	ALL AC220 @ 25mg/m^2/Day (Dose Level 1)	AML AC220 @ 25mg/m^2/Day (Dose Level 1)	ALL AC220 @ 40mg/m^2/Day (Dose Level 2)	AML AC220 @ 40mg/m^2/Day (Dose Level 2)	ALL AC220 @ 60mg/m^2/Day (Dose Level 3)	AML AC220 @ 60mg/m^2/Day (Dose Level 3)	ALL AC220 @ 90mg/m^2/Day (Dose Level 4)	AML AC220 @ 90mg/m^2/Day (Dose Level 4)	ALL AC220 @ 130mg/m^2/Day (Dose Level 5)	AML AC220 @ 130mg/m^2/Day (Dose Level 5)
Arm/Group Description	The starting dose is Dose Level 1 at 25 mg/m^2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age.	The starting dose is Dose Level 1 at 25 mg/m^2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age.	Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age.	Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age.	Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.	Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.	If the study dose of 60 mg/m^2/day at Dose Level 3 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 4 at 90 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 4 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.	If the study dose of 60 mg/m^2/day at Dose Level 3 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 4 at 90 mg/m^2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 4 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.	If the study dose of 90 mg/m^2/day at Dose Level 4 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 5 at 130 mg/m^2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. Dose Level 5 is the highest dose for this study.	If the study dose of 90 mg/m^2/day at Dose Level 4 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 5 at 130 mg/m^2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. Dose Level 5 is the highest dose for this study.
Period Title: Overall Study
STARTED	0	3	2	5	2	12	0	0	0	0
COMPLETED	0	3	2	4	0	10	0	0	0	0
NOT COMPLETED	0	0	0	1	2	2	0	0	0	0

Baseline Characteristics

Arm/Group Title	ALL AC220 @ 25mg/m2/Day (Dose Level 1)	AML AC220 @ 25mg/m2/Day (Dose Level 1)	ALL AC220 @ 40mg/m2/Day (Dose Level 2)	AML AC220 @ 40mg/m2/Day (Dose Level 2)	ALL AC220 @ 60mg/m2/Day (Dose Level 3)	AML AC220 @ 60mg/m2/Day (Dose Level 3)	Total
Arm/Group Description	The starting dose is Dose Level 1 at 25 mg/m^2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age.	The starting dose is Dose Level 1 at 25 mg/m^2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age.	Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age.	Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Cytarabine will be given to patients with AML on Day 0, dose assigned by age.	Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.	Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.	Total of all reporting groups
Overall Participants	0	3	2	5	2	12	24
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	13.1	2.8	13.1	2.8	13.1	11.6
Sex: Female, Male (Count of Participants)
Female	0 NaN	1 33.3%	2 100%	3 60%	1 50%	7 58.3%	14 58.3%
Male	0 NaN	2 66.7%	0 0%	2 40%	1 50%	5 41.7%	10 41.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 NaN	1 33.3%	1 50%	0 0%	1 50%	4 33.3%	7 29.2%
Not Hispanic or Latino	0 NaN	2 66.7%	1 50%	4 80%	1 50%	8 66.7%	16 66.7%
Unknown or Not Reported	0 NaN	0 0%	0 0%	1 20%	0 0%	0 0%	1 4.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 NaN	0 0%	0 0%	1 20%	0 0%	1 8.3%	2 8.3%
Asian	0 NaN	1 33.3%	0 0%	1 20%	0 0%	0 0%	2 8.3%
Native Hawaiian or Other Pacific Islander	0 NaN	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 NaN	0 0%	0 0%	0 0%	1 50%	0 0%	1 4.2%
White	0 NaN	2 66.7%	2 100%	2 40%	1 50%	8 66.7%	15 62.5%
More than one race	0 NaN	0 0%	0 0%	1 20%	0 0%	0 0%	1 4.2%
Unknown or Not Reported	0 NaN	0 0%	0 0%	0 0%	0 0%	3 25%	3 12.5%
# Patients with Prior HSCT (Count of Participants)
Count of Participants [Participants]	0 NaN	3 100%	0 0%	2 40%	0 0%	5 41.7%	10 41.7%
FLT3/ITD+ (FLT3-internal tandem duplication mutation) (Count of Participants)
Count of Participants [Participants]	0 NaN	2 66.7%	0 0%	3 60%	0 0%	5 41.7%	10 41.7%

Outcome Measures

1. Primary Outcome

Title	The Dose of AC220 That is Safe and Biologically Active When Given in Sequential Combination With Ara-C/Etoposide
Description	The incidence of dose limiting toxicity (DLT) will be measured. The maximum tolerated dose will be the highest study dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy. Plasma inhibitor activity (PIA) will be measured Pre-treatment and on Days 7, 14, 21 and 28 of Course 1. For the MTD to be considered biologically active, we will require that 7 of 9 patients achieve PIA of > 90% at 3 of 4 trough time points.
Time Frame	4 weeks from therapy start

Outcome Measure Data

Analysis Population Description

No patients with ALL were enrolled during Dose Level 1.

Arm/Group Title	ALL AC220 @ 25mg/m^2/Day (Dose Level 1)	AML AC220 @ 25mg/m^2/Day (Dose Level 1)	ALL AC220 @ 40mg/m^2/Day (Dose Level 2)	AML AC220 @ 40mg/m^2/Day (Dose Level 2)	ALL AC220 @ 60mg/m^2/Day (Dose Level 3)	AML AC220 @ 60mg/m^2/Day (Dose Level 3)
Arm/Group Description	The starting dose is Dose Level 1 at 25 mg/m2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age.	The starting dose is Dose Level 1 at 25 mg/m2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age.	Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age.	Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age.	Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.	Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.
Measure Participants	0	3	2	5	2	12
patient completed therapy without DLT	0 NaN	3 100%	1 50%	4 80%	0 0%	8 66.7%
patients experienced DLT	0 NaN	0 0%	1 50%	0 0%	0 0%	1 8.3%
patients withdrew or not evaluable	0 NaN	0 0%	0 0%	1 20%	2 100%	3 25%

2. Secondary Outcome

Title	Disease Response
Description	Possible outcomes are: Complete Remission (CR), Complete Remission without Platelet Recovery (CRp), complete response with incomplete hematologic recovery (CRi), Stable Disease, Progressive Disease, Induction Death, or Relapse
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

Five of 22 patients were not evaluable for response per protocol because they were removed from protocol therapy prior to disease assessment without meeting PD criteria

Arm/Group Title	Patients With ALL	Patients With AML Having FLT3-WT	Patients With AML Having FLT3-ITD
Arm/Group Description	Patients with a diagnosis of acute lymphocytic leukemia at study entry	Patients with a diagnosis of acute myeloid leukemia with internal tandem duplication (ITD) on exon 14 of the FLT3 gene	Patients with a diagnosis of acute myeloid leukemia having the FLT3 wild-type receptor (FLT3-WT)
Measure Participants	3	7	7
CR	0 NaN	1 33.3%	1 50%
CRi	0 NaN	0 0%	1 50%
CRp	0 NaN	0 0%	1 50%
SD	1 Infinity	5 166.7%	4 200%
PD	2 Infinity	1 33.3%	0 0%

3. Secondary Outcome

Title	Count of Participants According to Inhibition of FLT3 Phosphorylation
Description	PIA samples will be collected pre-treatment and on Days 7, 14, 21 and 28 of Course 1.
Time Frame	4 weeks from therapy start

Outcome Measure Data

Analysis Population Description

Nineteen of 22 patients had PIA assessment.

Arm/Group Title	Patients Receiving Protocol Therapy
Arm/Group Description	All patients receiving protocol therapy
Measure Participants	19
100% inhibition	9 Infinity
97-99% inhibition	9 Infinity
94% inhibition	1 Infinity

Adverse Events

Time Frame	Adverse events and suspected adverse reactions will be collected and reported on the electronic CRFs beginning with the first dose of study therapy until 30 days following the last dose of study therapy (a period of approximately 90 days).
Adverse Event Reporting Description	The definitions of AE and SAE do not differ from the clinicaltrials.gov definitions.
Arm/Group Title	ALL Dose Level 1		AML Dose Level 1		ALL Dose Level 2		AML Dose Level 2		ALL Dose Level 3		AML Dose Level 3
Arm/Group Description	The starting dose is Dose Level 1 at 25 mg/m^2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age.		The starting dose is Dose Level 1 at 25 mg/m^2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age.		Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age.		Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Cytarabine will be given to patients with AML on Day 0, dose assigned by age.		Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.		Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m^2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required.
All Cause Mortality
	ALL Dose Level 1		AML Dose Level 1		ALL Dose Level 2		AML Dose Level 2		ALL Dose Level 3		AML Dose Level 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		2/3 (66.7%)		2/2 (100%)		3/5 (60%)		1/2 (50%)		3/10 (30%)
Serious Adverse Events
	ALL Dose Level 1		AML Dose Level 1		ALL Dose Level 2		AML Dose Level 2		ALL Dose Level 3		AML Dose Level 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		2/3 (66.7%)		1/2 (50%)		3/5 (60%)		0/2 (0%)		4/10 (40%)
Blood and lymphatic system disorders
Febrile neutropenia	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	1/10 (10%)	1
Infection and Infestations - Rhinovirus	0/0 (NaN)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/10 (0%)	0
Infections and Infestations - Staphylococcus epidermidis	0/0 (NaN)	0	1/3 (33.3%)	1	1/2 (50%)	1	0/5 (0%)	0	0/2 (0%)	0	0/10 (0%)	0
Infections and Infestations - streptococcal pharyngitis	0/0 (NaN)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/10 (0%)	0
Infections and Infestations - Pseudomonas	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Gastrointestinal disorders
Pancreatitis	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	1/10 (10%)	1
General disorders
Chest wall pain	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/10 (0%)	0
Fever	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Immune system disorders
Anaphylaxis	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Infections and infestations
Infections and infestations - Other, Not Specified	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	2/10 (20%)	2
Lung infection	0/0 (NaN)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/10 (0%)	0
Sepsis	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Investigations
Blood bilirubin increased	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	1/10 (10%)	1
Lipase increased	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Metabolism and nutrition disorders
Hypokalemia	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Pulmonary edema	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Respiratory failure	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Skin & subcutaneous tissue disorder-Other	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/10 (0%)	0
Skin infection	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	2/5 (40%)	2	0/2 (0%)	0	0/10 (0%)	0
Vascular disorders
Hypotension	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	ALL Dose Level 1		AML Dose Level 1		ALL Dose Level 2		AML Dose Level 2		ALL Dose Level 3		AML Dose Level 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		3/3 (100%)		2/2 (100%)		5/5 (100%)		2/2 (100%)		10/10 (100%)
Blood and lymphatic system disorders
Anemia	0/0 (NaN)	0	3/3 (100%)	3	1/2 (50%)	1	4/5 (80%)	5	1/2 (50%)	1	6/10 (60%)	6
Febrile neutropenia	0/0 (NaN)	0	0/3 (0%)	0	1/2 (50%)	1	3/5 (60%)	3	1/2 (50%)	1	6/10 (60%)	6
Lymphocyte count decreased	0/0 (NaN)		2/3 (66.7%)	3	1/2 (50%)	1	3/5 (60%)	3	0/2 (0%)	0	5/10 (50%)	5
Neutrophil count decreased	0/0 (NaN)		1/3 (33.3%)	2	1/2 (50%)	1	2/5 (40%)	2	1/2 (50%)	1	6/10 (60%)	7
Platelet count decreased	0/0 (NaN)		2/3 (66.7%)	2	2/2 (100%)	2	3/5 (60%)	4	1/2 (50%)	1	7/10 (70%)	8
Strep Veridans Bacteremia	0/0 (NaN)		0/3 (0%)		0/2 (0%)		1/5 (20%)	1	0/2 (0%)	1	0/10 (0%)	1
Gastrointestinal disorders
Constipation	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	2/10 (20%)	2
Diarrhea	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Mucositis oral	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	2/5 (40%)	2	0/2 (0%)	0	0/10 (0%)	0
Nausea	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	1/10 (10%)	1
Rectal pain	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	2/10 (20%)	2
Vomiting	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Pancreatitis	0/0 (NaN)		0/3 (0%)		0/2 (0%)		0/5 (0%)		0/2 (0%)		1/10 (10%)	1
General disorders
Fever	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	3/10 (30%)	3
Pain	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	2/10 (20%)	2
Headache	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	2/5 (40%)	2	0/2 (0%)	0	0/10 (0%)	0
Tachypnea	0/0 (NaN)	0	0/3 (0%)	0	1/2 (50%)	1	1/5 (20%)	1	1/2 (50%)	1	1/10 (10%)	1
Rhinorrhea	0/0 (NaN)		0/3 (0%)		1/2 (50%)	1	0/5 (0%)	1	1/2 (50%)	1	0/10 (0%)	1
Irritation to central line site	0/0 (NaN)		0/3 (0%)		1/2 (50%)	1	0/5 (0%)	1	1/2 (50%)	1	0/10 (0%)	1
Infections and infestations
Catheter related infection	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	1/10 (10%)	1
Infections and infestations - Other - Not otherwise Specified	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	1/10 (10%)	1
Lung infection	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	1/10 (10%)	1
Device related infection	0/0 (NaN)		0/3 (0%)		0/2 (0%)		0/5 (0%)		0/2 (0%)		1/10 (10%)	2
Perirectal Abcess	0/0 (NaN)		0/3 (0%)		0/2 (0%)		0/5 (0%)		0/2 (0%)		1/10 (10%)	1
Blood Culture infection	0/0 (NaN)		2/3 (66.7%)	2	1/2 (50%)	1	0/5 (0%)	1	0/2 (0%)	1	1/10 (10%)	2
Investigations
Activated partial thromboplastin time prolonged	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	1/10 (10%)	1
Alanine aminotransferase increased	0/0 (NaN)	0	2/3 (66.7%)	2	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Alkaline phosphatase increased	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	1/10 (10%)	1
Aspartate aminotransferase increased	0/0 (NaN)	0	1/3 (33.3%)	1	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	2/10 (20%)	2
Blood bilirubin increased	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	1/10 (10%)	1
Creatinine increased	0/0 (NaN)	0	0/3 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/2 (0%)	0	0/10 (0%)	0
White blood cell decreased	0/0 (NaN)		3/3 (100%)	4	1/2 (50%)	1	5/5 (100%)	5	1/2 (50%)	1	6/10 (60%)	6
Metabolism and nutrition disorders
Anorexia	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	2/5 (40%)	2	0/2 (0%)	0	2/10 (20%)	2
Hyperglycemia	0/0 (NaN)	0	1/3 (33.3%)	1	0/2 (0%)	0	2/5 (40%)	2	0/2 (0%)	0	3/10 (30%)	3
Hypermagnesemia	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	1/10 (10%)	1
Hypoalbuminemia	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Hypocalcemia	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	1/2 (50%)	1	0/10 (0%)	0
Hypokalemia	0/0 (NaN)		0/3 (0%)	0	1/2 (50%)	1	2/5 (40%)	2	2/2 (100%)	2	9/10 (90%)	9
Hypomagnesemia	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	8/10 (80%)	8
Hyponatremia	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Hypophosphatemia	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	1/2 (50%)	1	1/10 (10%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/10 (0%)	0
Pain in extremity	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Hypoxia	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	4/10 (40%)	4
Sore throat	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	2	0/2 (0%)	0	0/10 (0%)	0
Skin and subcutaneous tissue disorders
Rash maculo-papular	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	2/10 (20%)	2
Skin & subcutaneous tissue disorder-Other - Not otherwise specified	0/0 (NaN)		1/3 (33.3%)	1	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/10 (0%)	0
Pilonidal cyst	0/0 (NaN)		0/3 (0%)		0/2 (0%)		0/5 (0%)		0/2 (0%)		1/10 (10%)	1
Erythmea	0/0 (NaN)		0/3 (0%)		1/2 (50%)	1	0/5 (0%)	1	0/2 (0%)	1	1/10 (10%)	1
Left neck peeling	0/0 (NaN)		0/3 (0%)		0/2 (0%)		1/5 (20%)	1	0/2 (0%)	1	0/10 (0%)	1
Drainage & reddened skin at Hickman CL site	0/0 (NaN)		0/3 (0%)		0/2 (0%)		0/5 (0%)		0/2 (0%)		1/10 (10%)	1
Ara-C Skin Rash	0/0 (NaN)		0/3 (0%)		1/2 (50%)	1	0/5 (0%)	1	0/2 (0%)	1	0/10 (0%)	1
Skin Nodules - Not otherwise specified	0/0 (NaN)		0/3 (0%)		1/2 (50%)	1	0/5 (0%)	1	0/2 (0%)	1	0/10 (0%)	1
Rash on Chest and Upper Arms	0/0 (NaN)		1/3 (33.3%)	1	0/2 (0%)	1	0/5 (0%)	1	0/2 (0%)	1	0/10 (0%)	1
Vascular disorders
Hypertension	0/0 (NaN)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/10 (0%)	0
Hypotension	0/0 (NaN)		0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	2/10 (20%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.