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.

PEVONEDISTAT-3001(NCT 03268954): Designed to evaluate the safety and efficacy of pevonedistat plus azacitidine versus single-agent azacitidine as a first-line treatment for patients with higher-risk myelodysplastic syndromes (HR MDS), chronic myelomonocytic leukemia (CMML), or low-blast acute myelogenous leukemia (AML)

Primary endpoint: Event-free survival (EFS)
Key secondary endpoint: Overall survival (OS)
Not a complete list of endpoints.

Enrolling countries
Australia, Belgium, Brazil, Canada, Czech Republic, France, Germany, Greece, Israel, Italy, Japan, Mexico, Poland, Russian Federation, South Korea, Spain, Turkey, UK, USA

For more information, including all inclusion and exclusion criteria
1-844-ONC-TKDA (1-844-662-8532) (US callers)
+1-510-740-1273 (ex-US callers)

www.clinicaltrials.gov or www.takedaoncology.com
For information on enrolling a patient, please contact GlobalOncologyMedInfo@takeda.com.

Pevonedistat is an investigational drug. Efficacy and safety have not been established.

Current Status: Part 1 recruitment complete; Part 2 (Phase 3) is now open for recruitment. For additional details, refer to the Geron press release (08 Aug 2019) at
http://ir.geron.com/news-releases/news-release-details/geron-starts-phase-3-clinical-trial-lower-risk-myelodysplastic

Geron Corporation 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 to be enrolled in the study. This study is being conducted at multiple hospitals and institutions around the world, in approximately 90 sites globally. For more information about this clinical study, please visit www.clinicaltrials.gov (NCT02598661).

Description: Guadecitabine (SGI-110) in MDS or CMML

Study Title: 408-Patient Multicenter, Randomized, Open-Label Study in Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML) After Failure of Prior Azacitidine, Decitabine, or both

For more information on this study and a full list of eligibility requirements please visit www.clinicaltrials.gov, Identifier: NCT02907359 or. ASTRAL-3@astx.com

Description: Oral ASTX727 LD in Lower Risk MDS

Study Title: A Randomized, Open-Label, Phase 1-2 Study of ASTX727 Low Dose (ASTX727 LD) Extended Schedule in Subjects With Lower Risk (IPSS Low or Intermediate-1) Myelodysplastic Syndromes (MDS)

For more information on this study and a full list of eligibility requirements please visit www.clinicaltrials.gov, Identifier: NCT03502668 or. ASTX727-03LD@astx.com

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.

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

MDSF Center of Excellence, Laura and Isaac Perlmutter Cancer Center at NYU Langone Health, is conducting a study on high dose vitamin C and its effect on the TET2 mutation in patients with MDS. Vitamin C may “tell” faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers. Certain genetic changes are known to reduce the ability of an enzyme called TET2 to encourage stem cells to become mature blood cells, which eventually die, in many patients with certain kinds of leukemia and MDS, say the authors. This new study found that vitamin C activated TET2 function in mice engineered to be deficient in the enzyme.

The team at Perlmutter Cancer Center hopes that high doses of vitamin C will eventually be incorporated into cancer therapies. Vitamin C in combination with cancer drugs may provide an alternative approach.

Would you like to participate in this clinical trial?

You may be eligible for this study if you meet the following criteria:

Conditions:

• Myelodysplastic Syndrome
• Between 18 – 99 Years
• Male or Female

Other Inclusion Criteria:

• Histologically confirmed Myelodysplastic Syndrome with positive TET2 mutations
• Myeloblasts account for less than 20% of leukocytes on peripheral blood and bone marrow aspirate
• Adequate organ function

You may not be eligible for this study if the following are true:

• Any cancer-related therapy for the current disease within 2 weeks of screening
• Requirement for systemic immunosuppressive therapy
• Uncontrolled concurrent serious illness

If you are interested, please contact the MDSF or the Center of Excellence directly (Dr. Raoul Tibes via email at Raoul.Tibes@nyulangone.org).

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).

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

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