DR LOVE: What kinds of trials are being looked at right now with all these different FLT3 inhibitors, including gilteritinib? What’s the strategy? How are the trials going to be run?

DR STONE: The trials that are looking for approval with gilteritinib and quizartinib are very similarly designed to each other. And they are both looking for single-agent approval based on Jorge’s data for the quizartinib and based on this data with the gilteritinib. Simply, it is, if you’ve got relapsed/refractory FLT3-mutant disease, for quizartinib it has to be ITD. For gilteritinib, it can be either the ITD or the TKD.

You’re randomized to the study drug, the FLT3 inhibitor, or dealer’s choice chemotherapy. And there’s a menu of chemotherapy options that people get in the control arm. These are big Phase III trials where survival is the primary endpoint. And we’ll see what happens.

DR CORTES: And I think that where these partnerships are not only feasible but now become critical is because now you’re not talking about a trial in AML. You’re talking about a trial on a subset of patients with AML. And if this trial took that long, if you were to do it in just a very confined environment, it’s impossible to accrue, because they’re so subset-defined.

DR STONE: So we need —

DR CORTES: — targets.

DR STONE: I think this brings up the notion that as a community, we can’t wait for 10 years, as Dr Ravandi asked me quite appropriately at the end of my talk at ASH, “Can we afford to wait another 10 years for a new drug?” And the answer is, of course, “No.”

So we need new trial designs, maybe MRD as an endpoint. If Drug A is better than Drug B, not by improving CR rate or survival, but if the MRD rate is lower with Drug B, then Drug B might be approved on that basis.

DR LOVE: What about getting community-based physicians being involved? Anything you want to comment on that or maybe ask them about that?

DR JOHL: Yes, the challenge is to certainly get these trials in the community setting. But I just want to go back to the comment earlier that leukemia is a very heterogeneous disease, and there’s a lot of different clones. So in the salvage setting, how come the FLT3 inhibitors are not being combined with chemotherapy for a better outcome?

DR STONE: They were. One was, at least. That was Levis’ trial that was MEC or high-DAC in relapsed AML, FLT3-positive, versus MEC or high-DAC plus lestaurtinib. And that was a negative trial, possibly just on the basis of the fact that the PK values for the lestaurtinib weren’t that great. In most of the patients, the drug levels weren’t high enough based on an assay that he did.

So I think they can be combined, and they should be combined. But when you’re in relapse, you’re likely to have a lot more mutations, a lot more resistance mechanisms than you did when you start out. So like any drug in oncology, as you well know, the best time to test it, if you can, is in the up-front situation.

I think it’s really critical that the trials are done in the community for 2 reasons. One, that gives patients who don’t live in Manhattan or in Back Bay, Boston to get access to a trial or can fly to Houston. B, that’s the real world. I mean, if an academic center like MD Anderson or Dana-Farber shows something’s good, sometimes it can’t be replicated in the community. Not because we’re lying, I hope, but because it’s a different patient — we have very select people who can make it to our institutions.

So to accomplish that, I think we need a couple of things. We need a different regulatory environment. The newest drugs can’t be given in the community, because the clinical trial requirements are so strict that it just can’t be shipped out. At Dana-Farber, we have a bunch of satellites that we actually own them. But because of regulations, it’s very difficult to open trials there.

I want to make a plug for Cooperative Group trials, because that’s the purpose of the Cooperative Group and the National Cancer Trials Network is to bring drugs to the community. Indeed, the work on the RATIFY trial that we talked about earlier, there were plenty of community practices that were involved in that.

But we really need a willingness of drug companies to work with public money to do these kinds of trials. And I hope that we can do more of that. The government’s talking about doing that. They have made the NCTN a more egalitarian system, but we need the drug companies to agree to go into that environment and so we can have more trials that can be done in the community.

Module 1: Current and future approaches to targeted therapy for acute myeloid leukemia (AML)

Module 2: Other clinical issues in AML management

Module 3: Case discussions