Trial Outcomes & Findings for Nivolumab and Oral Cyclophosphamide for R/R AML and HIgh Risk MDS (NCT NCT03417154)

NCT ID: NCT03417154

Last Updated: 2023-05-26

Results Overview

Number of participants with adverse events

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 12 participants
• Primary outcome timeframe: 4 weeks from start of treatment
• Results posted on: 2023-05-26

Participant Flow

Participant milestones

Measure	Arm 1: Nivolumab Every 2 Weeks and Cyclophosphamide Daily Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment	Arm 2: Nivolumab Every 2 Weeks and Cyclophosphamide Every 7 Days Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment
Overall Study STARTED	6	6
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	6	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Nivolumab and Oral Cyclophosphamide for R/R AML and HIgh Risk MDS

Baseline characteristics by cohort

Measure	Arm 1: Nivolumab Every 2 Weeks and Cyclophosphamide Daily n=6 Participants Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment	Arm 2: Nivolumab Every 2 Weeks and Cyclophosphamide Every 7 Days n=6 Participants Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks from start of treatment

Number of participants with adverse events

Outcome measures

Measure	Arm 1: Nivolumab Every 2 Weeks and Cyclophosphamide Daily n=6 Participants Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment	Arm 2: Nivolumab Every 2 Weeks and Cyclophosphamide Every 7 Days n=6 Participants Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment
Stage 1: Dosing Schedule of Low-dose Cyclophosphamide	6 Participants	6 Participants

PRIMARY outcome

Timeframe: 90 days from start of treatment

Overall response rate at 90 days from treatment start. Response is defined as CR + CRi + CRp + PR in AML and CR/PR/hematologic improvement (HI) in MDS.

Complete Remission (CR) - subjects must have bone marrow regenerating normal hematopoietic cells and achieve a morphologic leukemia-free state, an ANC > 1 x 109/L and platelet count ≥ 100 x 109/L and normal marrow differential with < 5% blasts, and they will be RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There should be no evidence of extramedullary leukemia

Complete Remission with Incomplete Hematologic Recovery (CRi) - subjects must fulfill all the criteria for CR except for incomplete hematological recovery

Complete Remission with Incomplete Platelet Recovery (CRp) - subjects must achieve CR except for incomplete platelet recovery

Partial Remission (PR) - subjects must have ≥50% bone marrow blast reduction or decrease to 5 to 25%

Outcome measures

Measure	Arm 1: Nivolumab Every 2 Weeks and Cyclophosphamide Daily n=6 Participants Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment	Arm 2: Nivolumab Every 2 Weeks and Cyclophosphamide Every 7 Days n=6 Participants Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment
Clinical Benefit and Immunologic Response of the Combination Therapy	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 30 days from start of treatment

Incidence of overall response.

Outcome measures

Measure	Arm 1: Nivolumab Every 2 Weeks and Cyclophosphamide Daily n=6 Participants Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment	Arm 2: Nivolumab Every 2 Weeks and Cyclophosphamide Every 7 Days n=6 Participants Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment
Objective Response Rate (ORR)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 6 months from start of treatment

Incidence of progression free survival.

Outcome measures

Measure	Arm 1: Nivolumab Every 2 Weeks and Cyclophosphamide Daily n=6 Participants Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment	Arm 2: Nivolumab Every 2 Weeks and Cyclophosphamide Every 7 Days n=6 Participants Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment
Progression Free Survival (PFS)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 6 months from start of treatment

Incidence of overall survival.

Outcome measures

Measure	Arm 1: Nivolumab Every 2 Weeks and Cyclophosphamide Daily n=6 Participants Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment	Arm 2: Nivolumab Every 2 Weeks and Cyclophosphamide Every 7 Days n=6 Participants Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment
Overall Survival (OS)	4 Participants	5 Participants

Adverse Events

Arm 1: Nivolumab Every 2 Weeks and Cyclophosphamide Daily

Serious events: 3 serious events

Other events: 4 other events

Deaths: 2 deaths

Arm 2: Nivolumab Every 2 Weeks and Cyclophosphamide Every 7 Days

Serious events: 5 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Measure	Arm 1: Nivolumab Every 2 Weeks and Cyclophosphamide Daily n=6 participants at risk Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment	Arm 2: Nivolumab Every 2 Weeks and Cyclophosphamide Every 7 Days n=6 participants at risk Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	16.7% 1/6 • Number of events 1 • Adverse events were collected from on treatment date up until 6 months after the off treatment date, on average of 1 year.	33.3% 2/6 • Number of events 2 • Adverse events were collected from on treatment date up until 6 months after the off treatment date, on average of 1 year.
Blood and lymphatic system disorders Febrile neutropenia	16.7% 1/6 • Number of events 3 • Adverse events were collected from on treatment date up until 6 months after the off treatment date, on average of 1 year.	33.3% 2/6 • Number of events 2 • Adverse events were collected from on treatment date up until 6 months after the off treatment date, on average of 1 year.
Infections and infestations Lung infection	16.7% 1/6 • Number of events 1 • Adverse events were collected from on treatment date up until 6 months after the off treatment date, on average of 1 year.	16.7% 1/6 • Number of events 1 • Adverse events were collected from on treatment date up until 6 months after the off treatment date, on average of 1 year.

Other adverse events

Measure	Arm 1: Nivolumab Every 2 Weeks and Cyclophosphamide Daily n=6 participants at risk Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment	Arm 2: Nivolumab Every 2 Weeks and Cyclophosphamide Every 7 Days n=6 participants at risk Nivolumab: 3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses. Low dose Cyclophosphamide (CTX): Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment
Gastrointestinal disorders GI Disorders	50.0% 3/6 • Number of events 3 • Adverse events were collected from on treatment date up until 6 months after the off treatment date, on average of 1 year.	100.0% 6/6 • Number of events 15 • Adverse events were collected from on treatment date up until 6 months after the off treatment date, on average of 1 year.
General disorders Edema limbs	33.3% 2/6 • Number of events 2 • Adverse events were collected from on treatment date up until 6 months after the off treatment date, on average of 1 year.	50.0% 3/6 • Number of events 3 • Adverse events were collected from on treatment date up until 6 months after the off treatment date, on average of 1 year.

Additional Information

Dr. Joseph Maakaron

University of Minnesota, Masonic Cancer Center

Phone: (612) 626-5654

Email: maaka001@umn.edu

Results disclosure agreements

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