Dose Escalation and Cohort Expansion Study of TEN-010 in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

The Weill Cornell Leukemia Program has recently opened a new clinical trial for men and women who have been diagnosed with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS). The study sponsor is Tensha Therapeutics, Inc. and the principal investigator at Weill Cornell is Dr. Gail Roboz. For more information about the study, please call Tania Curcio, RN at (212) 746-2571 or e-mail tjc9003@med.cornell.edu.

Key Eligibility

  • Men and women age 18 and older with a confirmed diagnosis of AML or MDS
  • Previously treated with at least one prior therapy
  • Subjects with a history of allogeneic (from another person) stem cell transplant are eligible for study participation
  • Life expectancy of at least 2 months
  • Detailed eligibility reviewed when you contact the study team

Study Details

This is a Phase 1, non-randomized, open-label, multi-center study that utilizes the investigational study drug TEN-010. TEN-010 belongs to a group of drugs called bromodomain inhibitors.  Bromodomains are found in cancer cells and bromodomain inhibitors may have promise as a therapy for patients who have cancer.  Currently, there are no bromodomain inhibitors approved by the FDA for humans. Research in the laboratory has shown that TEN 010 kills cancer cells in different types of both blood cancers.

The study is conducted in two parts; Part A and Part B. In Part A, escalating doses of TEN-010 will be administered to patients to evaluate safety and side effects that may limit the amount of TEN-010 given to patients. One of the goals of Part A is to establish the maximum tolerated dose (MTD) of TEN-010. Part B is an expansion study in which patients are treated at the MTD of TEN-010 to identify safety, tolerability, and how well the disease responds to treatment with TEN-010.

All subjects participating in this study will receive the study drug TEN-010 once daily. Subjects will be assigned to one of three different dose levels ranging from 0.06 mg/kg to 0.24 mg/kg .


New Clinical Trial: Randomized, Open Label, Phase 2 Study of Selinexor (KPT-330) vs Physician’s Choice in Patients Greater Than or Equal to 60 Years Old with Relapsed/Refractory Acute Myeloid Leukemia (AML) who are Ineligible for Intensive Chemotherapy and/or Transplant

The Weill Cornell Leukemia Program has recently opened a new clinical trial for men and women who have been diagnosed with Acute Myeloid Leukemia (AML). The study sponsor is Karyopharm Therapeutics and the principal investigator at Weill Cornell is Dr. Gail Roboz. For more information about the study, please call Tania Curcio, RN at (212) 746-2571 or e-mail tjc9003@med.cornell.edu.

Key Eligibility

  • Men and women age 60 and older with a confirmed diagnosis of AML
  • Previously treated with at least one prior therapy
  • Have not undergone and currently  ineligible for stem cell transplant and/or intensive chemotherapy
  • Have not been diagnosed with Acute Promyelotic Leukemia (AML M3),  Chronic Myeloid Leukemia (CML), and Central Nervous System Leukemia
  • Detailed eligibility reviewed when you contact the study team

Study Details

This randomized, open label study has been designed to assess whether Selinexor (KPT-330) can improve the overall survival in patients with relapsed or refractory AML who are not candidates for intensive chemotherapy. Selinexor (KPT-330) works by trapping “tumor suppressing proteins” within the cell and thus causing the cancer cells to die or stop growing.  The study drug has previously been tested in humans to define a safe dose to be administered. Selinexor is currently being tested in other clinical trials in patients with advanced cancers. This study will examine the effects of Selinexor on AML and the side effects that may occur as a result of treatment. It will also compare the effect of Selinexor with the effect of other existing treatments for AML that your physician can recommend.

Potential subjects will be enrolled in of two treatment groups:
Treatment group 1: In group 1, KPT-330 will be given orally (by mouth) twice weekly
Treatment group 2: In group 2, your physician will choose one of the following AML treatments that are currently available:

  • Best supportive care (BSC) including blood product transfusions, antimicrobial drugs, growth factors as needed, and hydroxyurea
  • BSC + low dose Ara-C given twice a day by subcutaneous injection
  • BSC + hypomethylating agent azacitidine given by subcutaneous injection or decitabine administered intravenously

Selinexor will be given orally twice weekly (Monday and Wednesday or Tuesday and Thursday) at a dose of 60-120 mg


Dr. Gail Roboz Discusses Challenges and Progress in Acute Myeloid Leukemia

When Gail J. Roboz, MD, took the stage Wednesday to give her talk on what’s ahead in the treatment of acute myeloid leukemia (AML), she admitted feeling a little jealousy toward her colleagues in the lymphoid diseases.

“AML continues to languish at the bottom of the survival curve. The lymphoid diseases are just doing so much better,” said Roboz, associate professor of Medicine and director of the Leukemia Program at the Weill Medical College of Cornell University and the NewYork-Presbyterian Hospital.

That is not to say, however, that research into myeloid diseases is “completely languishing,” Roboz stressed in her presentation at the 2014 Chemotherapy Foundation Symposium. Real progress has been achieved in understanding AML’s biology, and new targeted agents are being explored to improve outcomes.

For example, Roboz noted, mutations in FLT-3 (FMS-like tyrosine kinase 3) are associated with highly proliferative leukemia and adverse outcomes, while mutations in NPM1 (nucleophosmin 1) and biallelic mutations in CEBPA (CCAAT enhancer-binding protein a) have significantly more favorable survival.

“Although the mechanism of action of AML is much better understood, it’s not simple, and that’s the problem,” Roboz stressed.

Another challenge in treating patients with AML—which Roboz noted results in 10,000 deaths of the approximately 13,000 cases diagnosed each year—is whether more cases will be diagnosed, as patients survive other cancers. “We know that it’s associated with chemo and radiation exposure,” as well as other known environmental risk factors, genetic abnormalities, and benign and hematologic diseases also associated with AML.

Improving on Standard of Care
Although the current cytarabine-based 7+3 regimen remains the standard of care, “we do understand our weapon a little better, and this has certainly resulted in some survival benefit,” said Roboz, adding that this “much-worked-on regimen can be given to much older patients.”

Roboz, who will be leading an AML education session at the American Society of Hematology Annual Meeting in San Francisco next month, reviewed successive efforts by the German AML Study Group “to make chemo better,” through variations on (and additions to) the 7+3 dosing regimen, but these have led to what she described as “superimposable curves.”

“Is it in fact a triumph of hope over experience to add things on to 7+3?” This is a useful question, she elaborated, because “is it that we’re adding new things that aren’t new enough or are we adding them in the wrong place? It’s certainly concerning that all of these efforts over all of these years led to superimposable graphs.”

Other agents are pending, said Roboz, including clofarabine which, she said, “definitely works in AML, but we can’t quite get it right to be where it needs to be an approved drug for AML. We’re anxiously awaiting whether it can ‘beat’ 7+3,” she said.

A phase II study of CPX-351,1 which, Roboz explained, “is taking 7+3 and trying to make it better. This is a formulation that holds cytarabine and daunorubicin in a fixed 5:1 ratio, and we’re waiting to see whether what looked like a benefit in overall survival in a very difficult-to-treat population of secondary AML patients will hold up in a randomized trial, and whether taking the best regimen that we have and making the formulation better will get the job done.”

Roboz also hopes to have data available soon from the multicenter Alliance trial, looking at decitabine versus decitabine plus bortezomib in a 10-day schedule.

Looking ahead, said Roboz, “We have epigenetics, we have targeted therapies, personalized medicine. We must be on the way to improved therapeutic options.”

“Hope springs eternal. We want these agents to work and to synergize with our ‘best regimens,’” she said.


References

  1. 1. Lancet JE, Cortes JE, Hogge DE, et al. Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML [published online March 31, 2014]. Blood.

http://www.onclive.com/conference-coverage/cfs-2014/Roboz-Discusses-Progress-Challenges-in-AML


Dr. Gail Roboz, an associate professor of medicine, was elected chair of the 2014 American Society of Hematology Leukemia Education Session, which will take place during the society’s annual meeting in December in San Francisco. The meeting allows attendees to review more than 3,000 scientific abstracts and access a community of more than 20,000 international hematology experts covering every subspecialty. The American Society of Hematology is the world’s largest professional society concerned with the causes and treatments of blood disorders.


Dr. Gail Roboz to speak at free interactive conference in Philadelphia – Saturday, May 17

On Saturday, May 17, Dr. Gail Roboz will speak at a free interactive conference in Philadelphia for patients and families living bone marrow failure diseases http://bit.ly/1jaCJan The conference is sponsored by the Aplastic Anemia & MDS International Foundation (AA&MDSIF). If you’re in the Philadelphia area from 8:30a to 5p please join Dr. Roboz and other leading experts in what promises to be an engaging discussion to help families of and people living with cancer. For more information and to register: http://bit.ly/1jjQOMK


Dr. Gail Roboz talks with Robin Roberts on Good Morning America about Leukemia

Roboz & RobertsWatch Dr. Gail Roboz’s appearance on Good Morning America with Robin Roberts, where she discusses bone marrow transplants for leukemia and myelodysplastic syndrome (MDS). She also mentions CRUSH!!MDS http://www.crushmds.org/, a comprehensive clinical database initiated by Dr Roboz, M.D. on behalf of the MDS Clinical Research Consortium. The segment with Dr. Roboz starts with 4 minutes left in the video, which can be seen via this link. Photo by Ida Mae Astute/ABC


Dr. Ellen Ritchie Receives $112,200 Contribution to Leukemia Fighters from the Plumbing Industry Promotion Fund of the City of New York and the Association Contracting Plumbers of the City of New York

Leukemia Fighters Donation


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