Results from phase 1 of the MANIFEST clinical trial to evaluate the safety and tolerability of pelabresib in patients with myeloid malignancies

Eytan M. Stein, Amir T. Fathi, Wael A. Harb, Gozde Colak, Andrea Fusco & James K. Mangan

 

ABSTRACT

Pelabresib (CPI-0610), a BET protein inhibitor, is in clinical development for hematologic malignancies, given its ability to target NF-κB gene expression. The MANIFEST phase 1 study assessed pelabresib in patients with acute leukemia, high-risk myelodysplastic (MDS) syndrome, or MDS/myeloproliferative neoplasms (MDS/MPNs) (NCT02158858). Forty-four patients received pelabresib orally once daily (QD) at various doses (24–400 mg capsule or 225–275 mg tablet) on cycles of 14 d on and 7 d off. The most frequent drug-related adverse events were nausea, decreased appetite, and fatigue. The maximum tolerated dose (MTD) was 225 mg tablet QD. One patient with chronic myelomonocytic leukemia (CMML) showed partial remission. In total, 25.8% of acute myeloid leukemia (AML) patients and 38.5% of high-risk MDS patients had stable disease. One AML patient and one CMML patient showed peripheral hematologic response. The favorable safety profile supports the ongoing pivotal study of pelabresib in patients with myelofibrosis using the recommended phase 2 dose of 125 mg tablet QD.

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Three Key Relationships Bring New Drugs to the MPN Community

 Byline:  Ann Brazeau, CEO & Founder

MPN Advocacy and Education International prides itself on bringing the experts to the MPN Community to ensure they are receiving accurate and updated information about clinical trials, treatment options, quality of life issues, and everything that could affect them medically.  It also brings biopharmaceutical companies together with the researchers/clinicians at all of their programs in an effort to inform both physician and patient who is doing what in the laboratories around the world that could bring a new drug to commercialization for their use.

These three relationships are critical to new drug development.  Our Industry Partners’ research and development teams work tirelessly in their labs to find answers to perplexing questions myeloproliferative neoplasms present.  The MPN specialists who give so much of their time to speak at our programs, spend hours in their labs and also see patients throughout each day to understand the complexities of MPNs and how to best treat each patient, and many participate in heading trials at their academic and medical institutions.  Patients participate and commit to lengthy clinical trials to help discover what works and what doesn’t.  Without them, drugs would not be developed or approved. Drugs have to be tested for safety and efficacy in patients.  There is no way around this fact.  Hats off to those who volunteer to participate in clinical trials in hopes that the drug may one day benefit others who have the same condition as theirs.  Participation in a clinical trial is a major contribution to our society.

Learn more about MPN clinical trials

This intricate connection is the key to so many discoveries that have saved lives, cured the common headache, stopped seizures, and cured some cancers.  While preclinical research answers basic questions about a drug’s safety, it is not a substitute for studies of ways the drug will interact with the human body.  People living with a chronic disease, like an MPN, benefit enormously from the pipeline of medications brought to market by hard-working clinical researchers who design and carry out clinical trials that show promise after testing in animals.

Education is critical to the success of clinical trials and participation.  If physicians that treat you are not aware of the numerous trials currently underway, is it your responsibility to share what you know? We would say yes.  Our programs for physicians that treat MPN patients always includes updates about current trials to be sure they are made aware of every single trial in the MPN space.  This information coupled with site locations and trial criteria are essential to connecting the patient to a specific trial.

In this era of individualized treatment protocols and combination therapies, which will eventually be widespread in not only MPNs but other disease areas, it would be a shame to miss opportunities where potentially good therapies might fall off the grid for lack of trial participants and trial sites due to already strained programs.  With the robust activity in MPNs currently, the challenges accompany the gains.  Thus, the relationships among the three groups is even more important.

MPN Advocacy and Education International understands the challenges experienced by all three entities.  Each plays an integral role in bringing new drugs to the shelves and ultimately to patients.  Researchers who participate in trials and see patients can be overwhelmed.  Patients may have financial issues that prohibit a commitment to a trial even if they want to participate.  There are social and cultural factors that have historically left many trials with one demographic of participants, namely white, insured, and often retired.

The good news is organizations and our partners want to understand the challenges and want to help in all ways.  In the seventeen years I’ve been working in MPNs, I am seeing the fruits of our advocating and educational efforts not only for patients, but in our relationships with biopharmaceutical companies and the hundreds of physicians who are not necessarily MPN specialists that see MPN patients.  Our engagement and desire to grow a deeper understanding of the many challenges patients face has created a real interest in finding ways to close the gaps in areas of access, participation, education, and support.

Without collaboration and communication, the momentum needed for new drug development would quickly lose steam.  MPN Advocacy and Education International remains committed to providing a platform for the dialogue necessary to keep the wheels in motion.

View our MPN Clinical Trials 101 Webinar

 

 

A Caregiver’s Story: The Journey of a Spouse Through the Transplant Process

In March, MPN Advocacy & Education International highlighted the story of a recent stem cell patient, Andrea (click here to view story). This month, Andrea’s wife, Denise, shares her story as a caregiver in an interview with us. 

Andrea and Denise

How did you feel about your spouse’s decision to have a transplant? Were you apprehensive? 

I have been a part of Andrea’s medical journey since her diagnosis from ET to myleofibrosis.  I recall it took me about a week to learn how to pronounce the name correctly, and it has been an education ever since.  Being present during doctor appointments and multiple clinical trials provided first-hand information in addition to our ongoing discussions.  Observing and experiencing her five years of transfusion independence was a gift.  We took advantage of the opportunity to cycle and travel together and separately. Knowing the clinical trial would either end or the drug would quit working was only a matter of time.  And knowing how she physically felt prior to and after this time period played a role in my ‘wrapping my head’ around a possible future transplant.  All the while, we adjusted and modified activities as needed in order to continue allowing her to live life to the fullest.

When medications were no longer yielding the same results, and Andrea’s blood transfusions became more frequent, the doctors felt the alternatives were to continue clinical trials and hope for the best or discuss a stem cell or bone marrow transplant. I felt she was strong enough physically to beat the odds. It was now or never. I never doubted our decision, and have had no regrets.

How did you prepare yourself as a caregiver? 

In order to prepare, I scoured MD Anderson’s educational resources to understand what a ‘typical’ transplant journey would entail.  I developed multiple spreadsheets to track medications, nutrition, recovery, therapy, etc. I left the online myleofibrosis forum readings to Andrea as she would report her findings from reading first-hand accounts.  She also talked to many individuals who had had transplants, pummeling them with questions.

Another important piece of this journey was my mindset.  I focused on the end goal – her successful transplant and healthy recovery.  I looked at the journey in three parts:

  1. Pre-transplant
  2. Transplant/hospital stay
  3. Post-transplant

My goal was to have as much of her daily care and needs become second nature to me prior to her hospital release. When she was released, the additional environmental interaction was familiar without the distraction of ‘everything new all at one time’.

What tools did you find useful as the caregiver and advocate?

I created a 3-ring notebook with tabs to manage spreadsheets, medical records/test,  and doctor questions, so I could access information easily and quickly. I created a spreadsheet to track her medication schedule.  The purpose was to help me identify what was needed, including dosage when refilling medications both inside and outside the hospital. Click here to view medication tracker template. (For an Excel spreadsheet version of the attached please email kmichael@mpnadvocacy.com).

I also knew there was a good possibility that after her hospital release and within the first 100 days, she would have a trip to the emergency room and be re-admitted to the hospital.  Therefore, medications and ‘the notebook’ were kept in one location and easily picked up and transported with us.  The notebook was with us each time we visited the care team.

I created additional spreadsheets to help track:

  • Food and water daily intake and output. This is useful for doctor & nutrition appointments.
  • Daily stats: blood pressure, temperature, pain levels, exercise, spirometer therapy.  This is useful for tracking blood pressure and temperature anomalies.  Because if her temperature rose to a specific number, she had to go to the emergency room immediately.
  • Signs of graft vs host disease (GVHD).
  • I choose to stay in the hospital 24/7 to understand how the nursing staff/care team handled her care. This experience helped me understand her routine.
  • I figured if I learned her hospital routine, it would be familiar when she was released.
  • I used my smartphone and set alarms with labels so I knew what drugs were due when. (Used upon hospital release.)
  • I utilized Caring Bridge (www.caringbridge.org) to communicate Andrea’s transplant journey to her friends and family. My intent with each post was to create an engaging story yet convey “a day in her life” so everyone could get a sense of being there.

What was the most challenging part of your role and why?

Coming home and changing environments automatically kicked us back to normal behaviors and patterns. I felt we had to be more careful and diligent in preventing infection.  Even though we were home, I had to be more watchful because familiarity brings about a relaxed state.  Her immune system was developing and the risk of infection was too great.  Andrea quickly tired of me saying “No, you can’t do that or touch that.”

Once home, Andrea’s friends visited.  This was a considerable risk to her because the natural tendency is to hug and touch. To reduce her risk, we asked people to use hand sanitizer when they were around her.  We developed a routine where I would greet her friends first with a hug and explain she couldn’t hug yet. Andrea stood back a few feet to reduce her availability.

What I learned :

Every recovery and journey is different.

While it’s tempting, don’t measure your progress against someone else.  It’s your journey.  That goes for both the patient and caregiver!

The “notebook” was a great tool.  It kept us on schedule for all medications and were able to provide information to the doctors as needed.

The hospital care team staff is a critical part of your recovery.  Don’t opt for staying close to home if you feel a facility’s care team is better in another location.

Deciding where to have the transplant included researching the number of myleofibrosis transplants, versus other blood disease transplants, and the success that facility had.

Participate in the journey. I chose to shave my head at the same time Andrea did.  It sure made showering quick and easy!

Take in the outdoors and/or change the scenery.

Exercise or go for walks.  Listen to music.  Visit a friend. Go to the grocery store.  Do something to clear your head and regain perspective.

Have a confidante. It’s normal to question, or become frustrated, and to second guess.  But remember – it’s temporary.

You are the coach, cheerleader, and guardian all at once.  Embrace the many hats you will wear!

Click here to read Andrea’s Transplant Story 

MPN Patient Daily Stats 06-10-18