Description: 408-Patient multicenter, randomized, open-label study in myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) after failure of prior azacitidine, decitabine, or both.

Study Title: A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) versus Treatment Choice (TC) in Adults with Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML) Previously Treated with Hypomethylating Agents

For more information on this study and a full list of eligibility requirements please visit www.clinicaltrials.gov, identifier NCT02907359.

This agent is investigational, efficacy and safety have not been established. There is no guarantee that this agent will become commercially available.

Description: Multicenter, randomized, open-label, crossover PK study of ASTX727 versus IV decitabine.

Study Title: Phase 3, Randomized, Open-Label, Crossover Study of Oral ASTX727 (Cedazuridine and Decitabine Oral Fixed-Dose Combination) versus IV Decitabine in Subjects with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)

For more information on this study and a full list of eligibility requirements please visit www.clinicaltrials.gov, identifier NCT03306264.

This agent is investigational, efficacy and safety have not been established. There is no guarantee that this agent will become commercially available.

INternational Study of Phase III Intravenous RigosErtib

STUDY DESCRIPTION
A Phase III, international, randomized, controlled study of Rigosertib + best supportive care versus physician’s choice of treatment + best supportive care in patients with myelodysplastic syndrome (MDS) after failure of a hypomethylating agent (HMA).

PRIMARY ENDPOINTS
Overall survival in the intention-to-treat population and in patients with very high risk per the Revised International Prognostic Scoring System (Greenberg et al, Blood 2012).

INTERNATIONAL TRIAL
More than 200 trial sites, globally.

For additional information on this study, please call the INSPIRE help line at 1-267-759-3676 or visit www.clinicaltrials.gov, identifier: NCT02562443.

Rigosertib is an investigational agent and is not approved by the FDA or other regulatory agencies worldwide as a treatment for any indication.

A Phase 3, Randomized, Controlled, Open-label, Clinical Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Patients with Higher-Risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Low-Blast Acute Myelogenous Leukemia.

Takeda Pharmaceuticals International Inc. is initiating a Phase 3 clinical study with the study drug Pevonedistat. The purpose of this study is to evaluate the efficacy and safety of pevonedistat plus azacitidine versus single agent azacitidine in participants with higher-risk myelodysplastic syndromes, chronic myelomonocytic leukemia and low blast acute myelogeneous leukemia. This study will look at the overall response, event free survival, and overall survival in people who take pevonedistat and azacitidine when compared to people who take single agent azacitidine.

The study will enroll approximately 450 participants. Once enrolled, participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups in a 28 day treatment cycles: 

• Pevonedistat 20 mg/m2 and azacitidne 75 mg/m2 combination.
• Single agent azacitidine 75 mg/m2.

All participants will receive azacitidine via the intravenous or subcutaneous route. Participants randomized to the combination arm also will receive pevonedistat intravenous infusion).

This multi-center trial will be conducted worldwide.

Patients may qualify for this study if:

• 18 years of age or older.
• Patients have intermediate, high, or very high risk MDS or CMML, based on the Revised International Prognostic Scoring System (IPSS-R), a standard prognostic tool.
• Patients have low-blast AML defined as 20% to 30% myeloblasts in the bone marrow (Low-Blast AML) and ≤30% myeloblasts in the peripheral blood and considered appropriate for azacitidine based therapy.
  

  ---

In order to refer a patient with MDS, CMML, or low blast AML for enrollment to this study and review eligibility criteria, physicians/health care providers should visit: www.clinicaltrials.gov (NCT03268954)

Contact: Takeda Study Registration Call Center +1-877-825-3327; medicalinformation@tpna.com

Takeda Oncology is a trademark of Takeda Pharmaceutical Company Limited. Millennium Pharmaceuticals, Inc. is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. ©2016 Millennium Pharmaceuticals, Inc.

Study Description: A Phase 1/1b study for patients with MDS or AML that have been treated with at least one prior therapy and have a wild-type TP53 gene. MDS patients must have high-risk disease and have failed or relapsed after treatment with azacitidine or decitabine. Patients are being treated with the investigational drug ALRN-6924, either alone (MDS and AML patients) or in combination with a low dose of cytarabine (only MDS patients and some AML patients who recently transformed from MDS). Doses and schedules available may vary over time.

Study Title: A Phase 1/1b Open-Label Study to Determine the Safety and Tolerability of ALRN-6924 alone and in combination with cytarabine (Ara-C) in Patients with Relapsed/Refractory Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome with Wild-Type TP53

Key Inclusion Criteria:

• AML or high-risk MDS that is no longer amenable to standard therapies
• Confirmed or anticipated wild-type TP53
• ECOG (Eastern Cooperative Oncology Group) performance status 0-2
• Adequate liver and kidney function

Key Exclusion Criteria:

• Myelodysplastic/myeloproliferative neoplasms
• The required use of any concomitant medications that are predominantly cleared by hepatobiliary transporters, organic anion transporter polypeptide [OATP] members OATP1B1 and OATP1B3, on the day of or within 48 hours after an ALRN-6924 infusion
• Prior allogeneic stem cell transplantation
• Leukemic blast count >25,000/µl
• Deletion of chromosome 17, or del(17p), unless one WT TP53 allele has been maintained
• Acute promyelocytic leukemia or AML with del(5q)
• Current central nervous system leukemic involvement

For more information on this study and a full list of eligibility requirements please visit www.clinicaltrials.gov, identifier NCT 02909972.

This study is currently being conducted at : Institute for Translational Oncology Research , Greenville, SC; Moffitt Cancer Center, Tampa, FL; Montefiore Einstein Cancer Center Bronx, NY; Oregon Health and Science University, Portland, OR; Sarah Cannon Research Institution, Denver, CO; Sarah Cannon Research Institution, Nashville, TN.

ALRN-6924 is an investigational agent and is not approved by the FDA or other regulatory agencies worldwide as a treatment for any indication

A Phase 1 open-label, non-randomized immunotherapy trial to assess the safety of an adoptive T cell therapy for patients with higher risk myelodysplastic syndrome (MDS)

PersImmune, Inc., a San Diego based company founded in 2010, is developing a personalized adoptive cell therapy for myelodysplastic syndrome (MDS) using its proprietary PACTN (Personalized Adoptive immunotherapy by Cytotoxic T lymphocytes targeted to patient-specific neoplastic cell Neoantigens) technology. PACTN consists of an infusion of T cells that specifically recognize and destroy the patient’s neoplastic cells while sparing normal tissue. The therapy is intended for patients with intermediate, high, or very high risk MDS who have an inadequate response to or who decline standard therapy.

PersImmune has initiated enrollment of MDS patients in an open-label, non-randomized phase I clinical trial that will assess the safety of PACTN infusion for eligible patients. This approach uses patient’s own T-cells (collected when the patient is diagnosed with MDS) to target mutations uniquely expressed by the malignant cells but not by normal ones (MDS-specific). The primary endpoints of this trial are to assess the safety, tolerability and maximum tolerated dose of the T cell therapeutic product. The observational secondary endpoints include assessment of disease response and measurement of survival of the infused T cells.

The study will enroll 9 to 15 participants and is still recruiting new patients.

Eligibility criteria:

• 18 years of age or older with MDS, preferably higher risk and a candidate for hypomethylating therapy.
• IMPORTANT: Patients must first be enrolled in PersImmune’s blood collection protocol, at or shortly after initial diagnosis, in order for PersImmune to identify immunogenic MDS mutations and generate the PACTN T-cell product.
• Patients must be unresponsive to or decline standard MDS therapy (i.e., hypomethylating agents) and are not eligible for hematopoietic stem cell transplantation

Additional information for physicians and health care providers interested in referring a patient with MDS is available at www.clinicaltrials.gov (NCT03258359)

This study is currently being conducted at only at the University of California, San Diego, Medical Center, but additional sites in southern California are being recruited to participate.

PersImmune, Inc., a San Diego based company founded in 2010, is developing a personalized adoptive cell therapy for myelodysplastic syndrome (MDS) using its proprietary PACTN (Personalized Adoptive immunotherapy by Cytotoxic T lymphocytes targeted to patient-specific neoplastic cell Neoantigens) technology. PACTN consists of an infusion of T cells that specifically recognize and destroy the patient’s neoplastic cells while sparing normal tissue. The therapy is intended for patients with intermediate, high, or very high risk MDS who have an inadequate response to or who decline standard therapy.

PersImmune has initiated enrollment of MDS patients in an open-label, non-randomized phase I clinical trial that will assess the safety of PACTN infusion for eligible patients. This approach uses patient’s own T-cells (collected when the patient is diagnosed with MDS) to target mutations uniquely expressed by the malignant cells but not by normal ones (MDS-specific). The primary endpoints of this trial are to assess the safety, tolerability and maximum tolerated dose of the T cell therapeutic product. The observational secondary endpoints include assessment of disease response and measurement of survival of the infused T cells.

The study will enroll 9 to 15 participants and is still recruiting new patients.

Eligibility criteria:

• 18 years of age or older with MDS, preferably higher risk and a candidate for hypomethylating therapy.
• IMPORTANT: Patients must first be enrolled in PersImmune’s blood collection protocol, at or shortly after initial diagnosis, in order for PersImmune to identify immunogenic MDS mutations and generate the PACTN T-cell product.
• Patients must be unresponsive to or decline standard MDS therapy (i.e., hypomethylating agents) and are not eligible for hematopoietic stem cell transplantation

Additional information for physicians and health care providers interested in referring a patient with MDS is available at www.clinicaltrials.gov (NCT03258359)

This study is currently being conducted at only at the University of California, San Diego, Medical Center, but additional sites in southern California are being recruited to participate.

Myelodysplastic Syndromes (MDS) remain difficult to treat, in part because these blood disorders are rare and researchers don’t have enough samples from patients to study. The National Myelodysplastic Syndromes Natural History Study is a chance to help improve MDS treatment in the future. For the first time ever in the U.S., this study will collect information and samples from patients with MDS, and follow those patients for years to answer questions about what causes MDS, how it gets worse over time, and what treatments are most likely to work. This National Institutes of Health (NIH) sponsored study will create a public resource by collecting clinical information and blood, bone marrow, and tissue samples from up to 2,000 people with, or suspected to have, MDS.

You may be eligible for this study if you are at least 18 years old and either:

• Your doctor thinks you may have MDS and is planning to test your bone marrow

          OR

• Your doctor diagnosed you with MDS during the past 6 months but you have not yet been treated for MDS

If you participate in this study, you will receive your normal care and treatment from your doctor but will not receive additional treatment as part of this study. Instead, your normal care and treatment will be followed. This will also include following your quality of life during your time on the study.

For more information on the study, including how to find a participating hospital near you, please visit the study website at https://thenationalmdsstudy.net/ or https://clinicaltrials.gov/ (NCT02775383).

Current Status: Part 1 recruitment complete; Part 2 is not yet open for recruitment. For additional details, refer to the Geron press release (12Sep2016) at http://ir.geron.com/phoenix.zhtml?c=67323&p=irol-newsArticle&ID=2201055.

Janssen Research & Development, LLC is conducting a Phase 2/3 clinical study referred to as “IMerge”, with the study drug Imetelstat, which is a first-in-class telomerase inhibitor. With its novel mechanism of action, Imetelstat may provide clinical benefit to MDS patients. In this study, Imetelstat is administered as a 2-hour intravenous infusion every 28 days.

IMerge is a study for people with MDS who need blood transfusions due to anemia (low red blood cell counts). People with low or intermediate-1 risk MDS that has relapsed or is refractory to Erythropoiesis-Stimulating Agents (ESAs) treatment are enrolled in the study. This study is being conducted at multiple hospitals and institutions around the world, in approximately 80 sites globally.

For more information about this clinical study, please visit www.clinicaltrials.gov (NCT02598661).

This is a phase 2 study of selinexor for MDS patients (with up to 30% blasts) and CMML who have received prior decitabine or 5-azacytidine. The primary endpoint is to determine the response rate of this novel drug in patients who have refractory or relapsed disease after receiving either decitabine or 5-azacytidine.

Secondary Objectives of the study are to determine if selinexor improves the survival of people with MDS and CMML after receiving 5-azacytidine and CMML. Additional secondary endpoints include an assessment of response duration and tolerability of selinexor, and to perform research studies on blood and bone marrow samples to better understand the mechanism of selinexor in MDS and CMML.

ClinicalTrials.gov Identifier: 

NCT02228525

Now Enrolling: NCT02367456

Pfizer is conducting a clinical study to determine the safety, efficacy, PK and PD of Glasdegib (PF-04449913) or placebo when combined with azacitidine in patients with previously untreated Intermediate-2 or High Risk Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML) with 20-30% blasts and multi-lineage dysplasia, or Chronic Myelomonocytic Leukemia (CMML).

This study is being conducted at multiple hospitals and institutions around the world and includes two components: (a) a Phase 1b open -label safety lead in component and (b) a Phase 2 randomized double-blind component. In the Phase 1b component, approximately 10 patients will be enrolled and will receive Glasdegib (PF-04449913) and azacitidine and in the Phase 2 component, 160 patients will be randomized to receive to receive either Glasdegib (PF-04449913) (Arm A) or placebo (Arm B) in combination with azacitidine.

If you are a physician or health care provider and would like to refer a patient for enrollment into this clinical trial OR if you are an MDS, AML, or CMML patient please see additional information and contact details at the following websites:

• https://clinicaltrials.gov/ct2/show/NCT02367456
• https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1371012&StudyName=A%20STUDY%20OF%20PF%2004449913%20IN%20COMBINATION%20WITH%20AZACITIDINE%20IN%20PATIENTS%20WITH%20PREVIOUSLY%20UNTREATED%20INTERMEDIATE%202%20OR%20HIGH%20RISK%20MYELODYSPLASTIC