Nivolumab and Oral Cyclophosphamide for R/R AML and HIgh... | NCT03417154

NCT03417154

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
HM2017-33	Other Identifier	University of Minnesota Division of Hematology, Oncology and Transplantation

Status Module

Label	Type	Description	Intervention Names
Arm 1: Nivolumab every 2 weeks and Cyclophosphamide daily	Experimental		Drug: Nivolumab Drug: Low dose Cyclophosphamide (CTX) Daily
Arm 2: Nivolumab every 2 weeks and Cyclophosphamide every 7 days	Experimental		Drug: Nivolumab Drug: Low dose Cyclophosphamide (CTX) Every 7 Days

Name	Type	Description	Arm Group Labels	Other Names
Nivolumab	Drug	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.	Arm 1: Nivolumab every 2 weeks and Cyclophosphamide daily

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Stage 1: Dosing Schedule of Low-dose Cyclophosphamide	Number of participants with adverse events	4 weeks from start of treatment
Clinical Benefit and Immunologic Response of the Combination Therapy	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%	90 days from start of treatment

Secondary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR)	Incidence of overall response.	30 days from start of treatment
Progression Free Survival (PFS)	Incidence of progression free survival.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

≥18 years of age
Meets one of the following disease criteria:
- Primary (de novo) AML or higher-risk MDS with induction failure: No CR after 2 or more induction attempts with high dose chemotherapy or hypomethylating agents or other agents; no CR after 1 induction attempt and not eligible for a 2nd induction.. Higher risk MDS defined as risk score > 4.5 based on the revised IPSS criteria.
- Secondary AML (from antecedent hematologic malignancy or treatment-related): Not in CR after 1 or more cycles of chemotherapy.
- Relapsed AML: Blasts ≥5% in bone marrow or peripheral blood after prior attainment of CR; relapse at any time but currently ≥100 days following allogeneic HCT.
- Relapsed MDS: Morphologic evidence of relapse or increase in blasts ≥5% in bone marrow or peripheral blood after prior attainment of hematologic improvement; or partial or complete response ; relapse at any time but currently ≥100 days following allogeneic HCT..
ECOG Performance Status ≤ 2 - refer to Appendix II
Adequate organ function within 14 days of study registration defined as:
- Absolute Lymphocyte Count: ≥ 500 cells/mm3
- Hepatic: total bilirubin ≤ 3 x upper limit of institutional normal (ULN); ALT and AST ≤ 5 x ULN
- Renal: Serum creatinine ≤ 2 mg/dL
- Pulmonary: No oxygen requirement on room air or requiring ≤ 2L supplemental O2
Sexually active females of child bearing potential and males with partners of child bearing potential must agree to use effective contraception during therapy and continuing (23 weeks for females, 31 weeks for males) after the last dose of nivolumab
Voluntary written consent

Exclusion Criteria:

Pregnant or breastfeeding -The agents used in this study fall under Pregnancy Category D - Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. Women of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days of study drug administration.
Prior allogeneic hematopoietic stem cell transplantation within previous 100 days (note patients with a prior alloHSCT receive nivolumab at the reduced dose of 1 mg/kg)
Signs or symptoms of active graft versus host disease
Active pneumonitis or uncontrolled infection
Received chemotherapy drugs within previous 2 weeks
Estimated life expectancy <28 days in the opinion of the enrolling investigator

Name	Affiliation	Role
Fiona He, MD	Division of Hematology, Oncology and Transplantation, Masonic Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Minnesota Masonic Cancer Center		Minneapolis	Minnesota	55455	United States

Arm/Group Information

ID	Title	Description
FG000	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
FG001	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

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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
BG001

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Stage 1: Dosing Schedule of Low-dose Cyclophosphamide

Number of participants with adverse events

Posted

Count of Participants

Participants

4 weeks from start of treatment

ID	Title	Description
OG000	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
OG001	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

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	Neoplasms benign, malignant and unspecified (incl cysts and polyps)		Non-systematic Assessment

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	May 12, 2021	Feb 7, 2023	Prot_SAP_000.pdf
ICF	No	No	Yes	Informed Consent Form	Sep 23, 2021	Feb 7, 2023	ICF_001.pdf

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins