Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Nivolumab

Cyclophosphamide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment

Low dose Cyclophosphamide (CTX) Daily

Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment

Low dose Cyclophosphamide (CTX) Every 7 Days

Fiona He, MD

This is a phase II trial of nivolumab and low dose cyclophosphamide (CTX) when given in combination to patients with relapsed/refractory acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (MDS) who are not eligible for or decline hematopoietic stem cell transplant. It includes a randomized pilot sub-study during stage 1.

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

Nivolumab and Oral Cyclophosphamide for Relapsed/Refractory Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndrome (MDS)

Number of participants with adverse events

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%

Masonic Cancer Center, University of Minnesota

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 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 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment

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

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Joseph Maakaron

Stage 1: Dosing Schedule of Low-dose Cyclophosphamide

Clinical Benefit and Immunologic Response of the Combination Therapy

Objective Response Rate (ORR)

Progression Free Survival (PFS)

Overall Survival (OS)

Overall Study

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Leukemia, Myelomonocytic, Acute

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Chronic Disease

Disease Attributes

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Venetoclax

Azacitidine

Antimetabolites

Enzyme Inhibitors

Two dose levels of AMG 176 will be tested in Part 1A to find the optimal biological dose/minimum safe biologically effective dose (OBD/MSBED).

After the OBD is found in Part 1A, two dose levels of AMG 176 in combination with azacitidine will be tested in Part 1B to find the OBD/MSBED.

After the completion of Part 1, the Part 2 dose expansion phase will begin at the OBD/MSBED identified in Part 1.

Venetoclax-naïve and venetoclax-exposed R/R HR-MDS participants after HMA failure will be enrolled along with participants with newly diagnosed HR-MDS/CMML.

Administered as an intravenous (IV) infusion.

AMG 176

Administered as an IV infusion or subcutaneous (SC) injection.

The main objective is to assess the safety, tolerability, and efficacy of AMG 176 as monotherapy and in combination with the 7-day regimen of azacitidine for the treatment of Higher-Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia (HR-MDS/CMML).

This study is a Phase 1 clinical trial designed to assess the safety, tolerability, and efficacy of AMG 176 as monotherapy and in combination with the 7-day regimen of azacitidine for the treatment of HR-MDS/CMML. Participants will be treated with intravenous (IV) AMG 176 and IV or subcutaneous (SC) azacitidine.

AMG 176 With Azacitidine in Subjects With Myelodysplastic Syndrome /Chronic Myelomonocytic Leukemia

A Phase 1 Study of AMG 176 as Monotherapy and in Combination With Azacitidine in Higher-Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

As assessed according to the Uniform Response Criteria for Myelodysplastic/ Myeloproliferative Neoplasms (MDS/MPN).

As assessed according to the Uniform Response Criteria for MDS/MPN for R/R MDS/CMML participants.

Amgen

Recurrence

Anti-Infective Agents

Cytarabine

Decitabine

Bisantrene

Decitabine and cedazuridine drug combination

Antiviral Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Bisantrene infused daily for 7 days of induction cycle 1; followed by bisantrene infusion on Days 1 and 2 and cytarabine arabinoside continuous infusion on Days 1 to 5 of each consolidation cycle for up to 3 cycles.

Each cycle is 28 days, with a potential to expand to 42 days to allow for full hematologic recovery.

Decitabine/cedazuridine daily on Days 1-5, Bisantrene infusion on Days 3 and 5 in 28 day cycle. Treatment repeats every 28 days up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Each has potential to expand to 42 days to allow for full hematologic recovery.

Induction monotherapy cycle: IV bisantrene daily on Days 1 to 7, starting at 250 mg/m2 then adjusted to either 275 mg/m2 or 225 mg/m2 based on confirmed dose (Run-in) Consolidation combination cycle/s: IV bisantrene daily on Days 1 to 2

Bisantrene Dihydrochloride (high dose)

IV bisantrene at escalating doses for 3 dose levels of 50, 65, 85 mg/m2 on Days 3 and 5 until Maximum tolerated dose (MTD) reached.

Bisantrene Dihydrochloride (low dose)

Consolidation cycles: continuous IV cytarabine (100mg/m2) on Days 1 to 5

Cytarabine Hydrochloride

PO fixed-dose decitabine/cedazuridine 35/100 mg tablet daily for 5 days (Days 1 to 5), 1 hour prior bisantrene infusion

Decitabine and cedazuridine

Marinella Messina, PhD

This is a two strata Phase 1b study to assess the safety and efficacy of bisantrene (RC110) in combination with a) cytarabine arabinoside (Ara-C) treatment for patients with relapsed or refractory (R/R) Acute Myeloid Leukemia (AML) with extramedullary disease and able to tolerate intensive chemotherapy; b) in combination with decitabine/cedazuridune (ASTX727) new or relapsed or refractory AML or high risk MDS or CMML with extramedullary disease and unable or not willing to have intensive chemotherapy.

The study is a multicenter, open label in patients with haematological malignancy / myeloproliferative disease (AML, MDS and CMML) and extramedullary disease (EMD) investigating 2 treatment regimens:

1. Stratum 1 will investigate use of high dose intravenous (IV) bisantrene (RC110) in combination with IV Ara-C for R/R AML with EMD able to tolerate intensive chemotherapy. This includes a run-in stage to confirm the dose of bisantrene (RC110) for induction and in combination with Ara-C for consolidation cycles and an expansion and an expansion stage that will treat additional patients at the confirmed bisantrene dose for induction and in combination with Ara-C consolidation cycles;
2. Stratum 2 will investigate use lower doses intravenous (IV) bisantrene (RC-110) in combination with fixed-dose oral decitabine/cedazuridine (ASTX727) to determine the maximum tolerated dose (MTD) for new or R/R AML and HR-MDS/CMML unable to tolerate intensive chemotherapy.

Pre-screening will be conducted to identify patients with EMD diagnosed by standard clinical practice including histology and by fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F FDG-PET/CT) imaging.

A Study of Bisantrene Combined With Cytarabine or With Decitabine for Adult Subjects With Extramedullary AML and MDS

An Open-label Two Strata Study of Bisantrene in Combination With Cytarabine Arabinoside or Bisantrene in Combination With Oral Decitabine/Cedazuridine for the Treatment of Acute Myeloid Leukemia Patients With Extramedullary Disease

Maximum tolerated dose (MTD) based on occurence dose limiting toxicity (DLT) graded according to the National Cancer Institute Common Terminology Criteria (NCI CTCAE) for Adverse Events v5.0 after completion of 2 cycles of treatment

Morphological overall response, defined as complete remission (CR), CR with incomplete hematologic recovery or morphologic leukemia free state (MLFS), after completion of first treatment cycle 1

Assessed based on the occurence of non-hematological Dose limiting toxicity (DLT) as graded according to the National Cancer Institute Common Terminology Criteria (NCI CTCAE) for Adverse Events v5.0 at the completion of cycle 1.

Response is defined as MRD negativity with and without morphological complete remission (CR), at low level molcular MRD with CR and MRD relapse (coversion MRD negativity to positivity) at the completion of cycle 1

Response evaluation by 18F-FDG-PET/CT is based on the 5-point scale Deauville criteria for complete metabolic response (defined as Deauville Score (DS) 1, 2, or 3) or for partial metabolic response (defined DS of 4 or 5 with decrease in number or activity in bone marrow/EMD disease at the completion of cycles 1,2 and 4..

Dermal response based on improvement on the static investigator global assessment (IGA) 5-point disease severity scores, where higher score indicate more disease, defined as decrease of at least two points relative to baseline at the completion of cycles 1,2 3 and 4.

Dermal therapeutic improvement based on the static investigator global assessment (IGA) 5-point disease severity scores, where higher score indicate more disease, defined as decrease of at least two points relative to baseline at the completion of cycles 1,2 3 and 4.

Safety and tolerability based on the incidence and severity of adverse events assessed using National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] v5.0, grade per event, patient, and cycle of treatment.

Proportion of patients who receive subsequent allogeneic HSCT

EFS assessed between treatment start until the date of the earliest of these events: death, progression or off protocol-treatment for any reason using the Kaplan-Meier method

OS assessed between treatment start until death due to any cause using the Kaplan-Meier method

Morphological overall response, defined as either CR or CR as complete remission (CR), CR with incomplete hematologic recovery, CR with incomplete count recovery or MLFS. For patients with MDS/CMML, overall response, defined as either CR or modified CR mCR with haematological improvement (HI) at the end of cycle 1

Response is defined as MRD negativity with and without morphological complete remission (CR), at low level molecular MRD with CR and MRD relapse (coversion MRD negativity to positivity) at the completion of cycle 4.

Response evaluation by 18F-FDG-PET/CT, based on the 5-point scale Deauville criteria for complete metabolic response (defined as as Deauville Score (DS) 1, 2, or 3) or for partial metabolic response (defined as DS of 4 or 5 with decrease in number or activity in bone marrow/EMD disease) at the the completion of cycles 4, 6, 9 and 12

Dermal clinical improvement based on the static investigator global assessment (IGA) 5-point disease severity scores, where higher score indicate more disease, defined as as disease severity score of 1 (almost clear) or 0 (clear) and at least a two grade/point decrease in severity score relative to baseline the completion of cycles 4, 6, 9 and 12

Dermal therapeutic improvement based on the static investigator global assessment (IGA) 5-point disease severity scores, where higher score indicate more disease, defined as decrease of at least two points relative to baseline the completion of cycles 4, 6, 9 and 12.

EFS assessed between treatment start until the date of the earliest of these events: death, progression or off protocol-treatment for any reason assessed

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nivolumab and Oral Cyclophosphamide for R/R AML and HIgh Risk MDS	NCT03417154	Acute Myeloid L... Higher Risk Mye...	Nivolumab Low dose Cyclop... Low dose Cyclop...	18 Years -	Masonic Cancer Center, University of Minnesota
AMG 176 With Azacitidine in Subjects With Myelodysplastic Syndrome /Chronic Myelomonocytic Leukemia	NCT05209152	Higher Risk Mye... Chronic Myelomo...	AMG 176 Azacitidine	18 Years - 85 Years	Amgen
A Study of Bisantrene Combined With Cytarabine or With Decitabine for Adult Subjects With Extramedullary AML and MDS	NCT05456269	Acute Myeloid L... Recurrent Acute... Refractory Acut... Higher Risk Mye... Chronic Myelomo...	Bisantrene Dihy... Bisantrene Dihy... Cytarabine Hydr... Decitabine and ...	18 Years -	Race Oncology Ltd
A Study of Bisantrene Combined With Cytarabine or With Decitabine for Adult Subjects With Extramedullary AML and MDS	NCT05456269	Acute Myeloid L... Recurrent Acute... Refractory Acut... Higher Risk Mye... Chronic Myelomo...	Bisantrene Dihy... Bisantrene Dihy... Cytarabine Hydr... Decitabine and ...	18 Years -	Race Oncology Ltd
Nivolumab and Oral Cyclophosphamide for R/R AML and HIgh Risk MDS	NCT03417154	Acute Myeloid L... Higher Risk Mye...	Nivolumab Low dose Cyclop... Low dose Cyclop...	18 Years -	Masonic Cancer Center, University of Minnesota

Spots Global Cancer Trial Database for higher risk myelodysplastic syndrome