Trial Outcomes & Findings for Vincristine, Doxorubicin, And Dexamethasone + Ixazomib in Acute Lymphoblastic Leukemia (ALL), Lymphoblastic Lymphoma Or Mixed Phenotype Acute Leukemia (NCT NCT01887587)

NCT ID: NCT01887587

Last Updated: 2020-01-22

Results Overview

Safety, tolerability will be assessed by counting the number of participants experiencing adverse events at 8 weeks post treatment.

• Recruitment status: TERMINATED
• Study phase: PHASE1
• Target enrollment: 5 participants
• Primary outcome timeframe: Baseline to 30 days post treatment; approximately 8 weeks
• Results posted on: 2020-01-22

Participant Flow

Participant milestones

Measure	(Modified VXLD) Plus MLN9708 Vincristine-1.5 mg/m2 to a max dose of 2 mg IV on days 1, 8, 15 and 22 Dexamethasone- 10 mg/m2 orally or IV on days 1-14 Doxorubicin- 60 mg/m2 on day 1 by IV bolus. For patients without central nervous system (CNS) involvement: * Cytarabine 100 mg will be administered intrathecally on day 1 (+/-1 day) (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) * Methotrexate 12 mg will be administered intrathecally on day 8 (+/-1 day) For patients with CNS involvement: -Cytarabine 100 mg will be administered intrathecally on day 1 (+/-1 day) (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) Triple intrathecal chemotherapy with cytarabine 30 mg, methotrexate 15 mg and hydrocortisone 15 mg on (Day 1, 8, 15 and 22 (+/-1 day)).
Overall Study STARTED	5
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Vincristine, Doxorubicin, And Dexamethasone + Ixazomib in Acute Lymphoblastic Leukemia (ALL), Lymphoblastic Lymphoma Or Mixed Phenotype Acute Leukemia

Baseline characteristics by cohort

Measure	(Modified VXLD) Plus MLN9708 n=5 Participants Vincristine-1.5 mg/m2 to a max dose of 2 mg IV on days 1, 8, 15 and 22 Dexamethasone- 10 mg/m2 orally or IV on days 1-14 Doxorubicin- 60 mg/m2 on day 1 by IV bolus. For patients without CNS involvement: * Cytarabine 100 mg will be administered intrathecally on day 1 (+/-1 day) (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) * Methotrexate 12 mg will be administered intrathecally on day 8 (+/-1 day) For patients with CNS involvement: -Cytarabine 100 mg will be administered intrathecally on day 1 (+/-1 day) (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) Triple intrathecal chemotherapy with cytarabine 30 mg, methotrexate 15 mg and hydrocortisone 15 mg on (Day 1, 8, 15 and 22 (+/-1 day)). MLN9708 Vincristine Doxorubicin Dexamethasone
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	49 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 30 days post treatment; approximately 8 weeks

Population: At dose level one, 3 patients who were enrolled. The protocol was amended to remove PEGaspargase from the regimen. Two additional patients were enrolled on dose level one.

Safety, tolerability will be assessed by counting the number of participants experiencing adverse events at 8 weeks post treatment.

Outcome measures

Measure

(Modified VXLD) Plus MLN9708 n=5 Participants Vincristine-1.5 mg/m2 to a max dose of 2 mg IV on days 1, 8, 15 and 22 Dexamethasone- 10 mg/m2 orally or IV on days 1-14 Doxorubicin- 60 mg/m2 on day 1 by IV bolus. For patients without CNS involvement: * Cytarabine 100 mg will be administered intrathecally on day 1 (+/-1 day) (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) * Methotrexate 12 mg will be administered intrathecally on day 8 (+/-1 day) For patients with CNS involvement: -Cytarabine 100 mg will be administered intrathecally on day 1 (+/-1 day) (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) Triple intrathecal chemotherapy with cytarabine 30 mg, methotrexate 15 mg and hydrocortisone 15 mg on (Day 1, 8, 15 and 22 (+/-1 day)). MLN9708 Vincristine Doxorubicin Dexamethasone

Adverse Events.

5 participants

PRIMARY outcome

Timeframe: 8 Weeks

Population: All five subjects received the same 2.3 mg oral dose of MLN9708.

This measure will be the maximum tolerated dose (MTD) at which no more than 1 Dose Limiting Toxicity (DLT) is observed. The starting dose of MLN9708 will be 2.3 mg orally on days 1, 8 and 15. If no DLT is seen in the first 3 patients, the dose will be increased to 3 mg and then to 4 mg orally on days 1, 8 and 15 in a classic 3 +3 phase I design. We will not attempt to increase the dose beyond 4 mg orally which, if achieved with acceptable toxicity, would be accepted as the recommended phase 2 dose (RP2D). 0 of 3 DLTs would allow escalation to the next dose level. 1 of 3 DLTs will require expanding to six patients; 1 of 6 DLTs will allow escalation again. 2 DLTs will require dose de-escalation.

Outcome measures

Measure

(Modified VXLD) Plus MLN9708 n=5 Participants Vincristine-1.5 mg/m2 to a max dose of 2 mg IV on days 1, 8, 15 and 22 Dexamethasone- 10 mg/m2 orally or IV on days 1-14 Doxorubicin- 60 mg/m2 on day 1 by IV bolus. For patients without CNS involvement: * Cytarabine 100 mg will be administered intrathecally on day 1 (+/-1 day) (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) * Methotrexate 12 mg will be administered intrathecally on day 8 (+/-1 day) For patients with CNS involvement: -Cytarabine 100 mg will be administered intrathecally on day 1 (+/-1 day) (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) Triple intrathecal chemotherapy with cytarabine 30 mg, methotrexate 15 mg and hydrocortisone 15 mg on (Day 1, 8, 15 and 22 (+/-1 day)). MLN9708 Vincristine Doxorubicin Dexamethasone

Optimal Dose of MLN9708

2.3 mg

Adverse Events

(Modified VXLD) Plus MLN9708

Serious events: 4 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Measure	(Modified VXLD) Plus MLN9708 n=5 participants at risk Vincristine-1.5 mg/m2 to a max dose of 2 mg IV on days 1, 8, 15 and 22 Dexamethasone- 10 mg/m2 orally or IV on days 1-14 Doxorubicin- 60 mg/m2 on day 1 by IV bolus. For patients without CNS involvement: * Cytarabine 100 mg will be administered intrathecally on day 1 (+/-1 day) (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) * Methotrexate 12 mg will be administered intrathecally on day 8 (+/-1 day) For patients with CNS involvement: -Cytarabine 100 mg will be administered intrathecally on day 1 (+/-1 day) (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) Triple intrathecal chemotherapy with cytarabine 30 mg, methotrexate 15 mg and hydrocortisone 15 mg on (Day 1, 8, 15 and 22 (+/-1 day)). MLN9708 Vincristine Doxorubicin Dexamethasone
Blood and lymphatic system disorders Febrile neutropenia	20.0% 1/5 • 8 weeks following last dose.
Infections and infestations Sepsis	60.0% 3/5 • 8 weeks following last dose.
Investigations Methemoglobinemia	20.0% 1/5 • 8 weeks following last dose.
Cardiac disorders Sinus tachycardia	20.0% 1/5 • 8 weeks following last dose.
Hepatobiliary disorders Lactic acidosis	20.0% 1/5 • 8 weeks following last dose.
Hepatobiliary disorders Increased blood bilirubin	20.0% 1/5 • 8 weeks following last dose.
Vascular disorders Hypotension	20.0% 1/5 • 8 weeks following last dose.

Other adverse events

Adverse event data not reported

Additional Information

Ehab Atallah, MD

Medical College of Wisconsin

Phone: 414-805-8900

Email: eatallah@mcw.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place