Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Cytopenia

Thrombocytopenia

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Blood Platelet Disorders

Antineoplastic Agents

All Drugs and Chemicals

Azacitidine

Decitabine

Antimetabolites

Enzyme Inhibitors

500 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles

750 mcg AMG 531 weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles

750 mcg AMG 531 weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles

Placebo weekly via subcutaneous injection + 75 mg/m2 azacitidine for 4 cycles

Placebo weekly via subcutaneous injection + 20 mg/m2 decitabine for 4 cycles

Subjects in the control group will receive a placebo subcutaneous injection on a weekly basis during the 4 cycle treatment period.

Placebo

AMG 531 (Romiplostim) will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during Part A and 750 μg during Part B for the 4 cycle treatment period, depending on randomization.

AMG 531 (Romiplostim)

The purpose of this study is to evaluate the effect of Romiplostim (AMG 531) on the incidence of clinically significant thrombocytopenic events (grade 3 or 4 and/or receipt of platelet transfusions) in subjects with low or intermediate risk Myelodysplastic Syndrome (MDS) receiving hypomethylating agents. It is hypothesized that Romiplostim administration, at the appropriate dose and schedule, will result in reduction in the incidence of clinically significant thrombocytopenic events in low or intermediate risk MDS subjects receiving hypomethylating agents.

Determination of Safe and Effective Dose of Romiplostim (AMG 531) in Subjects With Myelodysplastic Syndrome (MDS)Receiving Hypomethylating Agents

A Randomized, Double Blind, Placebo Controlled Study Evaluating the Efficacy and Safety of Romiplostim (AMG 531) Treatment of Subjects With Low or Intermediate Risk Myelodysplastic Syndrome (MDS) Receiving Hypomethylating Agents

Occurrence of a clinically significant thrombocytopenic event within the participant, defined as any platelet count obtained from day 15 of cycle 1 through the end of the interim follow-up visit that was less than 50 x 10\^9/L or receipt of platelet transfusions at any time through the interim follow-up visit.

Occurrence of hypomethylating agent dose reduction and delay due to thrombocytopenia

CR = decrease in bone marrow blast (≤5%) and improvement in peripheral blood counts (Hgb ≥ 11 g/dL, platelets ≥ 100x10\^9/L, neutrophils ≥ 1x10\^9/L, peripheral blasts=0%). PR = improvement in peripheral blood counts plus a decrease in bone marrow blasts ≥50% but not ≤5, or decrease in International Prognostic Scoring System score.

Occurrence of one or more platelet transfusions from study day 1 through the interim follow-up visit (16 weeks)

Amgen

The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Part A Placebo

Part A Romiplostim 500 µg

Part A Romiplostim 750 µg

Part B Placebo

Part B Romiplostim 750 µg

Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 75 mg/m\^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A)

Romiplostim (AMG 531) Placebo Plus Azacitidine

500 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m\^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A)

Romiplostim (AMG 531) 500 mcg Plus Azacitidine

750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 75 mg/m\^2 azacitidine daily for 7 days during each of four 28-day cycles (Part A)

Romiplostim (AMG 531) 750 mcg Plus Azacitidine

Romiplostim (AMG 531) placebo weekly via subcutaneous injection plus 20 mg/m\^2 decitabine daily for 5 days during each of four 28-day cycles (Part B)

Romiplostim (AMG 531) Placebo Plus Decitabine

750 mcg romiplostim (AMG 531) weekly via subcutaneous injection plus 20 mg/m\^2 decitabine daily for 5 days during each of four 28-day cycles (Part B)

Romiplostim (AMG 531) 750 mcg Plus Decitabine

Total

Age, Continuous

Sex: Female, Male

White or Caucasian

Black or African American

Hispanic or Latino

Asian

Race/Ethnicity, Customized

Study Director

Full Analysis Set, composed of all randomized participants

Occurrence of a Clinically Significant Thrombocytopenic Event

Hypomethylating Agent Dose Reduction and Delay Due to Thrombocytopenia

Achieving an Overall Response (Complete or Partial Response, CR or PR) at the End of the Treatment Period

Platelet Transfusion

Part A

Part B

Cohort 1 in Part A, participants received romiplostim 300 µg subcutaneously once weekly for 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.

Cohort 2 in Part A, participants received romiplostim 700 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.

Cohort 3 in Part A, participants received romiplostim 1000 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.

Cohort 4 in Part A, participants received romiplostim 1500 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.

Part B participants received romiplostim 750 µg subcutaneously (SC) once weekly (QW) for 8 weeks. Participants who complete Part B could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.

Part B participants received romiplostim 750 µg subcutaneously every two weeks (Q2W) for 8 weeks. Participants who complete Part B could continue to receive injections of romiplostim for up to 1 year in the extension treatment phase.

Part B participants received romiplostim 750 µg intravenously (IV) once every two weeks for 8 weeks. Participants who complete Part B could continue to receive romiplostim for up to 1 year in the extension treatment phase.

Romiplostim

The purpose of this study is to evaluate the safety and tolerability of romiplostim in thrombocytopenic patients with low or Intermediate-1 risk MDS. In addition, the study will evaluate the platelet response to romiplostim.

Determination of Safe Dose of Romiplostim (AMG 531) in Patients With Myelodysplastic Syndromes (MDS)

An Open Label, Sequential Cohort, Dose Escalation Study to Evaluate the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

The number of participants experiencing one or more adverse events during the treatment phase or extension phase of Part A.

The number of participants experiencing one or more adverse events during the treatment phase or extension phase of Part B.

Participants with a complete or major response during the treatment phase. A complete platelet response was defined as a platelet count ≥ 100 x 10\^9/L during the treatment phase. A major platelet response was defined as an increase in absolute platelet count of ≥ 30 x 10\^9/L for patients starting with \> 20 x 10\^9/L platelets, or an increase from ≤ 20 x 10\^9/L to \> 20 x 10\^9/L and by at least 100%. Any participant receiving rescue medication was considered a non-responder. Platelet transfusions were considered rescue medication.

The number of participants with a platelet response according to the modified International Working Group (IWG) criteria. Response was defined as an absolute increase of ≥ 30 x 10\^9/L with Baseline platelet count \> 20 x 10\^9/L, or with a Baseline count ≤ 20 x 10\^9/L, increasing to above 20 x 10\^9/L and by at least 100% during the treatment or extension period and maintained for at least 8 consecutive weeks. Platelet transfusion was not considered a rescue medication but platelet counts ≤72 hours after platelet transfusion were excluded from the analysis.

Peak platelet count (10\^9/L) during the treatment period.

Participants achieving first platelet response according to IWG criteria, by study week. Platelet response was defined as an absolute increase of ≥ 30 x 10\^9/L with Baseline platelet count \> 20 x 10\^9/L, or with a Baseline ≤ 20 x 10\^9/L increasing the platelet count to above 20 x 10\^9/L and by at least 100% for 8 consecutive weeks. Platelet counts obtained within 72 hours of platelet transfusion were not evaluable for platelet response.

Duration of platelet response per IWG criteria (absolute increase of ≥ 30 x 10\^9/L with Baseline platelet count \> 20 x 10\^9/L, or with a Baseline ≤ 20 x 10\^9/L increasing the platelet count to above 20 x 10\^9/L and by at least 100% for 8 consecutive weeks).

Maximum observed serum concentration (Cmax) of romiplostim during Week 1

Measured romiplostim concentration at the end of the week 1 dosing interval (Ctrough)

Area under the romiplostim concentration-time curve from time zero to the last time point with quantifiable concentration (AUC0-4) during Week 1

Maximum observed serum concentration (Cmax) of romiplostim during Week 7.

Measured romiplostim concentration at the end of the Week 7 dosing interval (Ctrough)

Area under the romiplostim concentration-time curve from time zero to the last time point with quantifiable concentration (AUC0-4) during Week 7.

Time at which the maximum concentration of romiplostum was observed after subcutaneous administration during Week 1

Time at which the maximum concentration of romiplostum was observed after subcutaneous administration during Week 7

Cohort 1 in Part A participants received romiplostim 300 µg subcutaneously once weekly for 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.

Part A: 300 µg Romiplostim

Part A: 700 µg Romiplostim

Part A: 1000 µg Romiplostim

Part A: 1500 µg Romiplostim

Part B participants received romiplostim 750 µg subcutaneously (SC) once weekly (QW) for 8 weeks. Participants who completed Part B could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.

Part B: 750 µg Romiplostim SC QW

Part B participants received romiplostim 750 µg subcutaneously every two weeks (Q2W) for 8 weeks. Participants who completed Part B could continue to receive injections of romiplostim for up to 1 year in the extension treatment phase.

Part B: 750 µg Romiplostim SC Q2W

Part B participants received romiplostim 750 µg intravenously (IV) once every two weeks for 8 weeks. Participants who completed Part B could continue to receive romiplostim for up to 1 year in the extension treatment phase.

Part B: 750 µg Romiplostim IV Q2W

Cohort 1 in Part A, participants received romiplostim 300 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.

Japanese

American Indian or Alaska Native

Aborigine

Other

Efficacy Analysis Set, composed of all enrolled participants who received romiplostim and completed the treatment phase.

Part A: Number of Participants With a Complete or Major Platelet Response

Part B: Number of Participants With a Complete or Major Platelet Response

Subset of Efficacy Analysis Set, composed of all enrolled participants who received romiplostim and completed the treatment phase, who entered the treatment extension.

Part A: Number of Participants With a Platelet Response Per IWG Criteria

Efficacy Analysis Set, composed of all enrolled participants who received romiplostim and completed the treatment phase

Part B: Number of Participants With a Platelet Response Per IWG

Part B: Peak Platelet Count

Week 1 Day 3

Week 2

Week 3

Week 4

Week 5 or later

Not Observed

Part B: Time to First Platelet Response

Subset of Efficacy Analysis Set, composed of all enrolled participants who received romiplostim and completed the treatment phase, who had a platelet response

Part B: Duration of Platelet Response

Safety Analysis Set, composed of all enrolled participants who received at least one dose of romiplostim

Part B: Week 1 Cmax

Part B: Week 1 Ctrough

Part B: Week 1 AUC0-4

Part B: Week 7 Cmax

Part B: Week 7 Ctrough

Part B: Week 7 AUC0-4

Part B: Week 1 Tmax

Part B: Week 7 Tmax

All participants who received at least one dose of study medication

Part A: Number of Participants With Adverse Events

Part B: Number of Participants With Adverse Events

Treatment Period

Treatment Extension (Optional)

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Participants were treated with 600 mg orally, twice a day for 16 weeks, unless clear evidence of disease progression or toxicity was evident.

INCB024360 is an inhibitor of the enzyme indoleamine 2,3-dioxygenase (IDO) that is proposed for development for the treatment of malignant diseases. Participants were to receive the study drug in 28 day (4 week) cycles of treatment.

INCB024360

Rami Komrokji, M.D.

The primary purpose of this research study is to assess whether the participant's disease, Myelodysplastic Syndromes (MDS), responds favorably to INCB024360. The study will also evaluate the long-term outcomes of the participant's disease after they have finished taking INCB024360.

Phase II INCB024360 Study for Patients With Myelodysplastic Syndromes (MDS)

A Phase II Study to Determine the Safety and Efficacy of INCB024360 in Patients With Myelodysplastic Syndromes

ORR, measured by Response Criteria for Patients with Myelodysplastic Syndrome (MDS). According International Working Group (IWG) 2006 criteria (Cheson et al, 2006). Complete Remission (CR), Partial Remission (PR), Marrow CR, and Hematological Improvement (HI)(any cell line). Stable Disease (SD): Failure to achieve at least PR, but no evidence of progression for \> 8 weeks.

Disease progression defined as progression to int-2 or high risk International Prognostic Scoring System (IPSS) score or AML, based on World Health Organization (WHO) AML Criteria.

Overall Survival (OS) defined as the time between the start of treatment and death. Treatment Duration is 17 weeks plus optional continuation phase. Study Duration is Treatment Phase followed by survival follow-up.

Participants with treatment emergent Grade 3 or 4 SAEs according to the NCI Common Terminology Criteria for Adverse Events Version (CTCAE) V4.0.

Participants with treatment emergent Other (not including serious) Adverse events.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Determination of Safe and Effective Dose of Romiplostim (AMG 531) in Subjects With Myelodysplastic Syndrome (MDS)Receiving Hypomethylating Agents	NCT00321711	MDS Myelodysplastic... Thrombocytopeni...	Placebo AMG 531 (Romipl... Azacitidine Decitabine	18 Years -	Amgen
Determination of Safe Dose of Romiplostim (AMG 531) in Patients With Myelodysplastic Syndromes (MDS)	NCT00303472	Thrombocytopeni... MDS Myelodysplastic... Refractory Cyto...	Romiplostim	18 Years -	Amgen
Phase II INCB024360 Study for Patients With Myelodysplastic Syndromes (MDS)	NCT01822691	Myelodysplastic...	INCB024360	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Determination of Safe Dose of Romiplostim (AMG 531) in Patients With Myelodysplastic Syndromes (MDS)	NCT00303472	Thrombocytopeni... MDS Myelodysplastic... Refractory Cyto...	Romiplostim	18 Years -	Amgen

Spots Global Cancer Trial Database for refractory cytopenias