trialsTrialMixed

MORPHO

aka BMT CTN 1506, 2215-CL-0304

MORPHO asked whether taking the FLT3 blocker gilteritinib for two years after a stem-cell transplant keeps leukaemia from returning; across everyone the benefit fell just short of statistical proof, but in the half of patients whose blood tests still showed traces of leukaemia the drug clearly cut relapses.

MORPHO (BMT CTN 1506) was a double-blind, placebo-controlled phase 3 trial run by Astellas with the Blood and Marrow Transplant Clinical Trials Network. Adults with FLT3-ITD acute myeloid leukaemia in first remission who had undergone allogeneic transplant were randomised to gilteritinib or placebo for 24 months. The primary endpoint was relapse-free survival; measurable residual disease (MRD) for FLT3-ITD was assessed before and after transplant with a highly sensitive assay.

Relapse-free survival favoured gilteritinib but the difference was not statistically significant (hazard ratio 0.679, two-sided p 0.0518). About half of participants had detectable MRD before or after transplant, and in that prespecified subgroup gilteritinib halved the hazard of relapse or death, while patients without detectable MRD gained nothing. The trial is one of the first to support choosing post-transplant therapy by MRD, and the standard-of-care text for acute myeloid leukaemia describes FLT3 inhibitor maintenance after transplant for MRD-positive disease on this evidence.

Setting

FLT3-ITD acute myeloid leukaemia in first remission after allogeneic transplant: gilteritinib 120 mg or placebo daily for 24 months as post-transplant maintenance, with measurable residual disease measured before and after transplant

Phase

Phase 3

Sponsor

Astellas Pharma Global Development, Inc.

Registry

NCT02997202

Headline result

Relapse-free survival hazard ratio 0.679 for gilteritinib against placebo, not statistically significant overall; in the prespecified MRD-positive half of patients the hazard ratio was 0.515, with no benefit in MRD-negative patients.

Reported

2024

Enrolled

356 enrolled

Outcomes

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In plain words

What these results mean for people, not percentages

356 enrolled

Relapse-free survivalprimarysurrogate endpoint

The treated group had about 32 percent lower chance of the event at any given time (hazard ratio 0.679).
The absolute difference, how many more people out of 100 were helped, is not reported here.
Median not reached in either arm; 356 randomised

The likely range for the hazard ratio crosses 1, so the difference could be due to chance.

Relapse-free survival, MRD detectable before or after transplant (prespecified subgroup, 50.5% of participants)surrogate endpoint

The treated group had about 49 percent lower chance of the event at any given time (hazard ratio 0.515).
The absolute difference, how many more people out of 100 were helped, is not reported here.

Relapse-free survival, MRD not detectablesurrogate endpoint

The treated group had about 21 percent higher chance of the event at any given time (hazard ratio 1.213).
The absolute difference, how many more people out of 100 were helped, is not reported here.

The likely range for the hazard ratio crosses 1, so the difference could be due to chance.

Caveats

This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
These results apply to the people the trial enrolled: FLT3-ITD acute myeloid leukaemia in first remission after allogeneic transplant: gilteritinib 120 mg or placebo daily for 24 months as post-transplant maintenance, with measurable residual disease measured before and after transplant. People in a different situation may not see the same effect.
The trial selected people by a biomarker (FLT3); the result should not be assumed for people whose cancer does not have it.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

356 enrolled.

Relapse-free survivalprimary

HR 0.679 (0.459 to 1.005) · p = 0.0518

Median not reached in either arm; 356 randomised

Source

Relapse-free survival, MRD detectable before or after transplant (prespecified subgroup, 50.5% of participants)

HR 0.515 (0.316 to 0.838) · p = 0.0065

Numbers not yet public.

Source

Relapse-free survival, MRD not detectable

HR 1.213 (0.616 to 2.387) · p = 0.575

Numbers not yet public.

Source

Endpoint	Arm	n	Value	HR (95% CI)	p	Source
Relapse-free survivalprimary	Gilteritinib maintenance	-	Median not reached in either arm; 356 randomised	0.679 (0.459 to 1.005)	0.0518	link
Relapse-free survivalprimary	Placebo	-	-	0.679 (0.459 to 1.005)	0.0518	link
Relapse-free survival, MRD detectable before or after transplant (prespecified subgroup, 50.5% of participants)	Gilteritinib maintenance	-	-	0.515 (0.316 to 0.838)	0.0065	link
	Placebo	-	-	0.515 (0.316 to 0.838)	0.0065	link
Relapse-free survival, MRD not detectable	Gilteritinib maintenance	-	-	1.213 (0.616 to 2.387)	0.575	link
Relapse-free survival, MRD not detectable	Placebo	-	-	1.213 (0.616 to 2.387)	0.575	link

Key papers

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rctJournal of Clinical Oncology 2024changed practice187 citations

MORPHO: gilteritinib as post-transplant maintenance for FLT3-ITD acute myeloid leukaemia

Post-transplant FLT3 inhibitor maintenance helps patients with detectable FLT3-ITD residual disease and can probably be spared in those without it; guidelines now describe maintenance for MRD-positive disease on this evidence.