Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Antineoplastic Agents

All Drugs and Chemicals

Azacitidine

Antimetabolites

Enzyme Inhibitors

Combination of azacitidine at maximum tolerated dose and LDE255 at dose escalation, the starting dose will be 400 mg

Azacitidine at maximum tolerated dose. LDE255 at dose escalation (200, 400 or 800 mg)

Azacitidine and LDE255

Thomas PREBET, MD

Pierre FENAUX, MD, PHD

This study is a phase Ib add-on study of the combination of LDE255 to azacitidine in patients without marrow response after at least 6 cycles of azacitidine.

Dose escalation of LDE255 will be performed over time using a rolling 6 design to determine the safety of the combination with azacitidine. The starting dose will be 400 mg. Azacitidine will be continued at maximum tolerated dose (MTD). Evaluation will be based on cycle 1 toxicity profile. Once MTD will be determined, 20 additional patients will be treated at recommended dose.

A Study of LDE255 in Combination With Azacitidine for High Risk Myelodysplastic Syndrome Patients

A Single-arm Dose Finding Phase Ib Multicenter Study of the Oral Smoothened Antagonist LDE255 in Combination With Azacitidine for High Risk Myelodysplastic Syndrome Patients

Overall survival measured from the date of enrollment to death or the date of last contact

Novartis

Groupe Francophone des Myelodysplasies

Anti-Infective Agents

Decitabine

Thalidomide

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Angiogenesis Inhibitors

Growth Inhibitors

5-AZA-Cytidine 75mg/m2 5 days a month. 12 months. Thalidomide 50mg orally daily for 6 months.

5-aza-cytidine and Thalidomide

Moshe Mittelman, MD

Elizabeth Naparstek, MD

Study Objectives The aim of the study is to evaluate the safety and efficacy of the combination of 5-Aza-Cytidine + Thalidomide on the course of hrMDS patients.

Primary end point:

• To evaluate the overall response rate (CR+PR) of the combination of 5-Aza-Cytidine + Thalidomide in hrMDS patients (INT-2 and High risk as defined by IPSS).

Secondary end points:

* To evaluate the safety of the combination of Thalidomide+5-Aza-Cytidine in high risk MDS patients.
* Hematological improvement rate.
* Cytogenetic response.
* Progression free survival (PFS).
* Quality of life assessment (FACT: MDS and peripheral neuropathy QOL Questionnaires).

Study design:

This is a multicenter, phase II, single arm study designed to evaluate the safety and efficacy of the combination of Thalidomide+5-Aza-Cytidine in high risk MDS patients (INT-2 and High risk defined by IPSS) who are older than 18 years of age. Potential study subjects will sign an informed consent prior to undergoing any study related procedure. Number of patients to be enrolled 50.

Treatment plan: 5-aza-cytidine (75 mg m2/d) will be injected subcutaneously in 5-day cycle every 28 days, for a total of 12 cycles.

Thalidomide will be given at the dose of 50 mg/d, from day 1 until for 6 months together with 5-aza-cytidine .

Treatment period includes 5-aza-cytidine (75 mg m2/d) will be injected subcutaneously in 5-day cycle every 28 days. Total number of 12 cycles or until progression or toxicity. Cycle delay of maximum 2 weeks in case of hematological toxicity grade 3-4 at investigator discretion.

Duration of the follow up period is 6 months. Duration of study The duration of the treatment period is approximately 12 months. This time is required to complete the treatment, and to determine the safety profile and the response rate. The duration of the Follow period will be approximately a half year. The occurrence of PD will determine the duration of progression-free survival of each patient.

Safety and Efficacy of Azacitidine, and Thalidomide in Higher Risk MDS (Myelodysplastic Syndrome)

A Phase 2, Single Arm Study to Determine the Safety and Efficacy of Azacitidine, and Thalidomide in Higher Risk Myelodysplastic Syndrome

Tel-Aviv Sourasky Medical Center

Micronutrients

Deferasirox

Iron

Chelating Agents

Iron Chelating Agents

azacitidine 75mg/m2 7 days/28 day cycle deferasirox 10 mg/kg/day

SC or IV AZA at 75mg/m2 7 days/28 day cycle

SC or IV AZA at 75mg/m2 7 days/28 day cycle DFX 10mg/kg/day

Azacitidine plus Deferasirox

Novartis Pharmaceuticals

The primary objective of the study is to compare the overall response rate (inclusive of complete response, partial response and hematologic improvement) per IWG 2006 criteria in patients with higher risk MDS treated with azacitidine with or without deferasirox achieved over the course of one year. Hematologic improvement must be maintained for at least 8 weeks.

Phase II Study to Evaluate Overall Response in Patients With Higher Risk Myelodysplastic Syndromes (MDS) Treated With Azacitidine With or Without Deferasirox.

A 2-year, Multi-center, Phase II, Open-label, Fixed-dose, Randomized Comparative Trial of Azacitidine, With or Without Deferasirox in Patients With Higher Risk Myelodysplastic Syndromes

ORR (inclusive of CR, PR and HI) per IWG 2006 criteria including erythroid response, platelet response and neutrophil response over the course of one year. Hematologic improvement must be maintained for at least 8 weeks in order to count as HI.

Time to response is defined as time from the date of the first dose of study treatment to the date of the first documented hematologic improvement.

Duration of response is defined as time from the date of the first observed hematologic improvement to the date of the first subsequent documented disease progression or relapse per IWG 2006 criteria.

Progression free survival is defined as time from the date of the first dose of study treatment to the date of the first documented disease progression or relapse per IWG 2006 criteria.

Overall survival is defined as time from the date of the first dose of study treatment to the date of death from any cause.

Time to AML transformation is defined as time from the date of the first dose of study treatment to the date of the first documented bone marrow blast count ≥ 20% per WHO classification 1999.

Incidence of adverse events (AEs) overall and by severity, and serious adverse events (SAEs).

Median number of infections (positive bacterial, viral or fungal culture, or infection requiring IV antimicrobial, or infection resulting in hospitalization or death) in patients treated with azacitidine alone vs. azacitidine + deferasirox

Prevalence of the following mutations in the study population (TP53, EZH2, ETV6, RUNX1, ASXL1, other mutation that is present in ≥ 5% of patients)

Age, Categorical

Sex: Female, Male

No conclusion pertaining to efficacy and/or safety was drawn, only one patient was randomized to the study and their study participation was terminated prematurely due to fatal outcome of SAE.Only one patient in trial.No analysis will ever be done.

Clinical Disclosure Office

Only one patient in trial. No analysis will ever be done.

Overall Response Rate Per IWG 2006 Criteria

Time to Response

Duration of Response

Progression Free Survival

Overall Survival

Time to AML Transformation

Change in Serum Ferritin

Incidence of Adverse Events

Rate of Infection

Prevalence of MDS/AML Related Gene Mutations

Overall Study

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Panobinostat

Histone Deacetylase Inhibitors

10mg upto 40mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every week; duration: one year

Start of Arm B after completion of Arm A; initial dose-level: one level below MTD of Arm A; 10mg upto 60mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every other week; duration: one year

Gesine Bug, MD

The study's primary objective is to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of Panobinostat when administered within 150 days after hematopoietic stem cell transplantation (HSCT) and given in conjunction with standard immunosuppressive therapy after HSCT for patients with high-risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML).

Secondary objectives are

* To determine safety and tolerability of panobinostat
* To determine overall and disease-free survival at 12 months after HSCT
* To evaluate immunoregulatory properties of panobinostat
* To evaluate patient-reported health-related quality of life (HRQL)

The hypothesis of this study is that panobinostat can be an effective drug in preventing relapse of MDS and AML patients with high-risk features after hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC-HSCT) while at the same time reducing graft-versus-host disease (GvHD) with preservation of graft-versus-leukemia (GvL) effect.

Phase I/II Study With Oral Panobinostat Maintenance Therapy Following Allogeneic Stem Cell Transplantation in Patients With High Risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)

Phase I/II Study With Oral Panobinostat Maintenance Therapy Following Allogeneic Stem Cell Transplantation in Patients With High Risk MDS or AML (PANOBEST)

Johann Wolfgang Goethe University Hospital

Senior physician hematology

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Lirilumab by vein over about 60 minutes 1 time each 28 day cycle.

Nivolumab by vein over about 60 minutes every 2 weeks during Cycles 1-9. Lirilumab by vein over about 60 minutes 1 time each cycle. Cycle is 28 days.

Azacitidine by vein over about 60 minutes on Days 1-7 of each 28 day cycle. Lirilumab by vein over about 60 minutes on Day 7 of each 28 day cycle.

Azacitidine by vein over about 60 minutes on Days 1-7 of each 28 day cycle. Lirilumab by vein over about 60 minutes on Day 7 of each 28 day cycle. On Days 7 and 21 of Cycles 1-9 and then on Day 7 of Cycles 10 and beyond, Nivolumab by vein over about 60 minutes.

Lirilumab

3 mg/kg by vein on Days 7 and 21 of a 28 day cycle.

75 mg/m\^2 by vein for 7 days of a 28 day cycle.

Guillermo Garcia-Manero, MD

The goal of this clinical research study is to learn if lirilumab and Opdivo (nivolumab), alone or in combination with Vidaza (azacitidine), can help to control MDS. The safety of these drug combinations will also be studied.

This is an investigational study. Lirilumab is not FDA approved or commercially available. It is currently being used for research purposes. Nivolumab is FDA approved and commercially available for the treatment of melanoma and non small cell lung cancer (NSCLC). Azacitidine is FDA approved and commercially available for the treatment of MDS. The study doctor can explain how the study drugs are designed to work.

Up to 80 participants will be enrolled in this study. All will take part at MD Anderson.

Study Groups and Study Drug Administration:

If you are found to be eligible to take part in this study, you will be assigned to 1 of 2 study groups based on the status of the disease and then you will be assigned to a cohort based on when you join this study. Each study group will be made up of 2 cohorts. Group 1 is made up of Cohorts A and B. Group 2 is made up of Cohorts C and D. Each cohort will enroll up to 20 participants each.

Each study cycle is 4 weeks.

If you have low risk (low or intermediate-1) MDS, you will be enrolled in Group 1.

* If you are assigned to Cohort A, you will receive lirilumab by vein over about 1 hour 1 time each cycle.
* If you are assigned to Cohort B, you will receive nivolumab by vein over about 1 hour every 2 weeks during Cycles 1-9 and then 1 time each cycle after that. You will also receive lirilumab by vein over about 1 hour 1 time each cycle.

If you have high risk MDS, you will be enrolled in Group 2.

* If you are assigned to Cohort C, you will receive azacitidine by vein for up to 40 minutes on Days 1-7 of each cycle. You will also receive lirilumab by vein over about 1 hour on Day 7 of each cycle.
* If you are assigned to Cohort D, you will receive azacitidine by vein for up to 40 minutes on Days 1-7 of each cycle. You will receive lirilumab by vein over about 1 hour on Day 7 of each cycle. On Days 7 and 21 of Cycles 1-9 and then on Day 7 of Cycles 10 and beyond, you will also receive nivolumab by vein over about 1 hour.

If you are assigned to Cohorts B or D, you will need to stay in the clinic for up to 1 hour after your dose of nivolumab so the study staff may check your vitals and monitor your health for any side effects.

Both you and the study doctor will know to which group you have been assigned.

Study Visits:

One (1) time each week during Cycle 1 and then 1 time during each cycle after that:

* You will have a physical exam.
* Blood (about 2-3 teaspoons) will be drawn for routine tests. These tests may be done more often if your doctor thinks it is needed.

If the doctor thinks it is needed, on Day 28 of Cycle 1 and then every 3 months after that, you will have a bone marrow aspiration to check the status of the disease and for cytogenetic testing.

Every 6 weeks, if you can become pregnant, blood (about 1 teaspoon) or urine will be collected for a pregnancy test.

Length of Study:

You may continue receiving the study drug(s) as long as the study doctor thinks it is in your best interest. You will no longer be able to take the study drug(s) if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

You participation on this study, if you cannot become pregnant, will end after your last dose of study drug(s). If you can become pregnant, your participation on this study will be over after the follow-up pregnancy tests.

Follow-Up Pregnancy Tests:

If you can become pregnant, at 30 days and 70 days after you have stopped taking the study drug(s), blood (about 1 teaspoon) or urine will be collected for a pregnancy test.

Lirilumab and Nivolumab With 5-Azacitidine in Patients With Myelodysplastic Syndromes (MDS)

Phase II Combination of Lirilumab and Nivolumab With 5-Azacitidine in Patients With Myelodysplastic Syndromes (MDS)

Overall response rate (ORR) defined as complete response plus partial response (CR + PR) and hematological improvement (HI). MDS International Working Group criteria used to assess response.

Bristol-Myers Squibb

M.D. Anderson Cancer Center

Initially, a sample size of 20 patients for each cohort was planned, but the enrollment was stopped after the sponsor's decision not to pursue the development of lirilumab for myeloid malignancies. The study did not enroll long enough to reach the arms that combined Nivolumab + Lirilumab +/- Azacitidine.

Lirilumab by vein over about 60 minutes 1 time each 28 day cycle.

Lirilumab: 3 mg/kg by vein every 4 weeks.

Low or Intermediate-1 MDS Group - Lirilumab

Nivolumab by vein over about 60 minutes every 2 weeks during Cycles 1-9. Lirilumab by vein over about 60 minutes 1 time each cycle. Cycle is 28 days.

Lirilumab: 3 mg/kg by vein every 4 weeks.

Nivolumab: 3 mg/kg by vein on Days 7 and 21 of a 28 day cycle.

Low or Intermediate-1 MDS Group - Nivolumab + Lirilumab

Azacitidine by vein over about 60 minutes on Days 1-7 of each 28 day cycle. Lirilumab by vein over about 60 minutes on Day 7 of each 28 day cycle.

Lirilumab: 3 mg/kg by vein every 4 weeks.

Azacitidine: 75 mg/m\^2 by vein for 7 days of a 28 day cycle.

High Risk MDS Group - Azacitidine + Lirilumab

Azacitidine by vein over about 60 minutes on Days 1-7 of each 28 day cycle. Lirilumab by vein over about 60 minutes on Day 7 of each 28 day cycle. On Days 7 and 21 of Cycles 1-9 and then on Day 7 of Cycles 10 and beyond, Nivolumab by vein over about 60 minutes.

Lirilumab: 3 mg/kg by vein every 4 weeks.

Nivolumab: 3 mg/kg by vein on Days 7 and 21 of a 28 day cycle.

Azacitidine: 75 mg/m\^2 by vein for 7 days of a 28 day cycle.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of LDE255 in Combination With Azacitidine for High Risk Myelodysplastic Syndrome Patients	NCT02323139	MDS	Azacitidine and...	18 Years -	Groupe Francophone des Myelodysplasies
Safety and Efficacy of Azacitidine, and Thalidomide in Higher Risk MDS (Myelodysplastic Syndrome)	NCT00704704	Myelodysplastic...	5-aza-cytidine ...	18 Years -	Tel-Aviv Sourasky Medical Center
Safety and Efficacy of Azacitidine, and Thalidomide in Higher Risk MDS (Myelodysplastic Syndrome)	NCT00704704	Myelodysplastic...	5-aza-cytidine ...	18 Years -	Tel-Aviv Sourasky Medical Center
Phase II Study to Evaluate Overall Response in Patients With Higher Risk Myelodysplastic Syndromes (MDS) Treated With Azacitidine With or Without Deferasirox.	NCT02159040	High Risk MDS	Azacitidine Azacitidine plu...	18 Years - 80 Years	Novartis
Phase I/II Study With Oral Panobinostat Maintenance Therapy Following Allogeneic Stem Cell Transplantation in Patients With High Risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)	NCT01451268	Myelodysplastic... Acute Myeloid L...	Panobinostat Panobinostat	18 Years -	Johann Wolfgang Goethe University Hospital
Lirilumab and Nivolumab With 5-Azacitidine in Patients With Myelodysplastic Syndromes (MDS)	NCT02599649	Leukemia	Lirilumab Nivolumab Azacitidine	18 Years -	M.D. Anderson Cancer Center
Lirilumab and Nivolumab With 5-Azacitidine in Patients With Myelodysplastic Syndromes (MDS)	NCT02599649	Leukemia	Lirilumab Nivolumab Azacitidine	18 Years -	M.D. Anderson Cancer Center
Phase II Study to Evaluate Overall Response in Patients With Higher Risk Myelodysplastic Syndromes (MDS) Treated With Azacitidine With or Without Deferasirox.	NCT02159040	High Risk MDS	Azacitidine Azacitidine plu...	18 Years - 80 Years	Novartis
A Study of LDE255 in Combination With Azacitidine for High Risk Myelodysplastic Syndrome Patients	NCT02323139	MDS	Azacitidine and...	18 Years -	Groupe Francophone des Myelodysplasies
Safety and Efficacy of Azacitidine, and Thalidomide in Higher Risk MDS (Myelodysplastic Syndrome)	NCT00704704	Myelodysplastic...	5-aza-cytidine ...	18 Years -	Tel-Aviv Sourasky Medical Center

Spots Global Cancer Trial Database for high risk mds