CPI-0610

                      Well, not a memorable name, that, but hopefully a memorable and successful clinical trial. The study protocol just changed and the dosage increased. Funny thing: the drug is so new the manufacturers haven’t started making higher dose capsules (25 mg is the higest), so David will be taking 12 capsules of unusual size every morning.

            A not-so-funny thing: here’s the warning in the description: “In case of contact with the powder: wash skin immediately with soap and copious amounts of water for at least 15 minutes. If in eyes, rinse with copious amounts of water for at least 15 minutes.”

Here’s the study description of the drug:

CPI-0610 is a small molecule inhibitor of a group of proteins called BET proteins. By blocking BET proteins from binding to certain cancer-causing genes, CPI-0610 may result in these genes being deactivated (switched off). CPI-0610 has shown anti-tumor activity in previous laboratory studies.

(By the way, technically, individual leukemic blood cells are ‘tumors’. The name isn’t exclusive to solid masses.)

            The cycles are 21 days long. He takes the capsules for two weeks, then has a week off (of pill taking; he’ll still visit clinic twice a week). In this first cycle, he’ll have his blood drawn on Day 15 through 19. (Actually, he gets Sunday off.)

Today, Day One, we’ve spent the whole day at the clinic, from 7:30 a.m. to 5 p.m. There have been blood draws, after the first daily dose, at ½, 1, 1 ½, 2, 3, 4, 6, and 8 hours and EKGs (electrocardiogram, which measures electrical activity of the heart) at 1, 2, 4, and 6 hours. The portable EKG machine comes right to the room, so we’ve stayed in room 138 all day. Actually, midday I took the T to Harvard station and walked to the Cambridge Public Library to pick up a score of the Brahms’ German Requiem. We’re attending a concert on April 11^th and I want to learn the music better. I then walked down Broadway from the library to Kendall (the MIT stop). I was going to walk across the Longfellow Bridge, but it started to rain, so I bailed and took the T across the Charles River.

Tomorrow, Day Two, we’ll come in the morning for a blood draw at the 24 hour mark (plus or minus 3 hours, a comfortable window).

            From MGH we’ll drive to Logan airport and pick up Annie at noon. We’ll spend the day with her. Saturday Jim and I fly to Chicago and Annie and David drive to New York City to visit R’el, Peter, Xiomara, and Andrew. David gets a reprieve and doesn’t have to come back to clinic until Tuesday.

No More Decitabine

                   Our optimism about the decitabine took a nosedive today. Although David went through the fourth round without hydroxyurea, today the white blood cell counts are up again: from 8.93 last Thursday to 18.39 on Monday and a whopping 46.07 today. Yes, we’re back to doubling in 3 days. He’ll take 2 gram/day of hydroxyurea again and discuss clinical trial options on Monday. The hydroxyurea can keep the white blood counts low in the short term, but since it doesn’t attack the leukemia factory in the bone marrow, it can’t cure the leukemia.

He had another echocardiogram today: his heart’s poor ejection fraction barred him from certain clinical trials back in August. We hope he has recovered sufficiently to be eligible for a trial now, since the conventional treatments have not been effective in achieving remission.

He also had a bone marrow biopsy today. It was originally scheduled to assess the effect of the decitabine, but based on the blood draws we can see it isn’t working at this point. The clinical trials require biopsies to assess eligibility, so Judy took extra samples for those. We’ll get the preliminary results on Monday, as well as the echocardiogram results.

Jim and I are planning a trip to the Midwest starting 28 March. Originally we envisioned a road trip so that David could come, but he can’t be away from MGH for more than 5 days, so we’ll fly, see Annie in Madison, and Matt and Charlotte in Chicago. If Matt can arrange his schedule, we’ll drive to Wabash College in Crawfordsville, northwest of Indianapolis, where Matt is an admissions officer.

Date of Blood Draw (CBC)	White Blood Cell Count	% Blasts in circulation	Absolute Neutrophils	Hematocrit (red blood cells)
13-Feb-15	3.53	31.0%	0.39	19.40
19-Feb-15	5.89	30.0%	0.47	22.40
23-Feb-15	10.02	25.5%	1.60	21.20
26-Feb-15	9.97	53.0%	1.20	18.20
2-Mar-15	5.48	32.4%	0.51	24.40
5-Mar-15	4.09	28.6%	0.97	22.90
9-Mar-15	5.40	30.3%	1.14	20.40
12-Mar-15	8.93	60.0%	0.54	26.10
16-Mar-15	18.39	56.0%	1.84	23.60
19-Mar-15	46.07	67.0%	4.15	21.20

Decitabine: Hypomethylating Agent

            We saw Dr. Fathi yesterday. David asked him: since the decitabine seems to be effective, would he have chosen it as the initial treatment. He said no: the 7-3 cytarabine/daunorubicin regimen that David started nearly a year ago at Walter Reed is the standard first-line treatment for someone of David’s age with AML (acute myeloid leukemia). Over the whole population it has a remission rate of about 70%. And David did achieve remission from it, it just relapsed. Decitabine therapy has a remission rate of 40% or less. So, based on statistics, which is all we have to go on, the treatment choice was reasonable. Of course, for each individual patient, the remission rate is either zero or 100 percent.

            The current decitabine infusion therapy isn’t technically chemotherapy. At high doses, decitabine can be used as chemotherapy, with the goal of killing leukemic cells (and healthy blood, hair, and gut cells as collateral damage). But at this lower dose, it’s a “hypomethylating agent”. The theory is that the decitabine can reactivate tumor suppression genes in individual cells (cool, huh?) and thus allow the leukemic blasts to mature into healthy cells.

For five days, February 23 through 27, we went to Cox 1 each day for the fourth round of decitabine infusion therapy. The next bone marrow biopsy, probably in about three weeks, will indicate how well the decitabine is working. It will also show the status of the various mutations involved. The bone marrow has its own ecology, like a garden. David has multiple mutations of his white blood cells, like a garden with a variety of weeds. If you pull out one type of weed, there’s the danger that another, existing weed will invade the newly cleared area. Unfortunately, we don’t know how to pull out all the weeds at the same time or speed the spread of beneficial plants.

And speaking of gardens, today we had a thaw: 40 degree weather and puddles in our driveway. Still plenty of snow, but in March there’s always hope of spring.

Last week we had some excitement. My idyllic afternoon dishwashing was interrupted by a sudden crash and breaking glass. My first thought was that a giant icicle (we have several) had hit our bay window. But the staircase landing was full of glass and snow, no ice. Looking through the shattered window, we saw a 12 foot piece of our gutter forming an upside-down V in a snowbank. Roof snow had melted and refrozen into a heavy ice dam on top of the gutter. The ice was probably a few hundred pounds. The weight had broken the gutter in two and sent one piece careening to the ground, bashing the window on its descent. The remaining partial gutter, also full of heavy ice, hung directly over the power line to our house. A contractor friend came to the rescue and successfully removed the gutter. He also gave us some insulating foam board to cover the window until we can get it repaired. Was someone talking about gardens?