Phase I Trial of Brentuximab Vedotin With Re-induction Chemotherapy in Patients With Relapsed, CD30 Expressing, Acute Myeloid Leukemia (AML)
If patients agree to participate in this research study they will be asked to undergo some
screening tests or procedures to determine eligibility. Many of these tests and procedures
are likely to be part of regular cancer care and may be done even if it turns out that
patients do not take part in the research study. If patients have had some of these tests or
procedures recently, they may or may not have to be repeated. These tests and procedures
will include: a medical history, physical exam, performance status, pregnancy test, urine
test, electrocardiogram, echocardiogram, blood tests, and bone marrow aspirate/biopsy. If
these tests show that patients are eligible to participate in the research study, they will
begin the study treatment. If patients do not meet the eligibility criteria, they will not
be able to participate in this research study.
To start re-induction therapy, patients will receive brentuximab vedotin alone on Day 1.
They will begin treatment with MEC (mitoxantrone, etoposide and cytarabine) a few days later
(on Day 3). Since investigators are looking for the highest dose at which brentuximab
vedotin can be safely administered with MEC without severe or unmanageable side effects in
those with AML, not everyone who participates in this research study will receive the same
dose of the study drug. The dose a patient receives will depend on the number of
participants who have been enrolled in the study before that patient and how well they have
tolerated their doses.
For this study, treatment will be broken up into segments. Study treatment will occur in two
segments: 1) Re-Induction Therapy; and 2) Maintenance Therapy. Re-induction therapy, as
described above, will be the combination of brentuximab vedotin followed on day 3 by MEC
chemotherapy. The maintenance phase of therapy will only include brentuximab vedotin
administered every 21 days for a total period of 12 months, and does not include any other
chemotherapy. The treatment and assessments that may be required fo patients during these
phases of therapy are explained below. The following assessments will be completed while
patients are on the trial: physical exam, performance status, urine test, blood tests and
bone marrow aspirate/biopsy.
The first part of the study treatment is called "re-induction". During re-induction,
patients will be admitted to the Massachusetts General Hospital and will receive study
treatment on an in-patient basis. Patients will receive brentuximab vedotin IV
(intravenously or through a vein) alone on Day 1. They will then receive the following
standard drugs (the MEC regimen) starting on day 3. This regimen includes the chemotherapy
drugs mitoxantrone, etoposide, and cytarabine, all given by IV and beginning on Day 3 and
continuing through Day 7.
If at the end of the re-induction course, the number of leukemia cells have not decreased as
much as expected or desired, patients will be removed from the study and given alternative
The second part of study treatment is called "maintenance" and can be given on an outpatient
basis in clinic. During maintenance, patients will be administered brentuximab vedotin once
every 21 days, at the same dose as that given during the re-induction course. This 21 day
period will be called a cycle, and will be repeated until 12 months have passed from the
start of the maintenance therapy phase. During this phase, participants will not receive
other chemotherapies and will not be hospitalized for treatment. During the maintenance
phase, investigators will continue to collect approximately 2 to 3 teaspoons of blood for
research purposes every 3-4 weeks.
Investigators would like to keep track of patients' medical condition and overall health
following the 12 months of treatment on study. Investigators may ask patients questions
about their general health, current medications and disease status. Investigators will also
check on any new anticancer therapy patients may have started.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Define Maximum Tolerated Dose of Brentuximab Vedotin + MEC
The primary objective of this trial is to define the maximum tolerated dose (MTD) of the CD30 antibody drug conjugate brentuximab vedotin in combination with MEC re-induction chemotherapy in patients with relapsed acute myeloid leukemia and expression of CD30.
Amir Fathi, MD
Massachusetts General Hospital
United States: Food and Drug Administration
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|