Ivosidenib as Post-HSCT Maintenance for AML
A Randomized, Placebo-Controlled Phase 2 Study of IDH1 Inhibition Using Ivosidenib as Maintenance Therapy for IDH1-mutant Acute Myeloid Leukemia Following Allogeneic Stem Cell Transplantation
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years to 75 Years
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Time periods mentioned: 24 months
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "The estimated length of participation in the study is 3.5 years from screening to the end of planned follow-up, including up to 24 months of study treatment."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This Phase 2 study compares ivosidenib with a placebo, a pill with no active drug, after a donor stem cell transplant. It is for adults with acute myeloid leukemia (AML), a blood cancer, that has a change in the IDH1 gene. Ivosidenib blocks the changed IDH1 protein.
This is a Phase 2 study of the study drug, ivosidenib (a mutant IDH1 inhibitor), compared to placebo, given to patients with IDH1-mutant acute myeloid leukemia (AML) after hematopoietic stem cell transplantation (HCT).
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be 18 to 75 years old and have confirmed AML with the IDH1(R132) gene change.
- Plan to have a stem cell transplant from a donor.
- Be able to care for yourself and be out of bed for at least half of your waking hours.
- Meet blood count, liver, and kidney test limits. Before joining, you must have had no drugs to boost infection-fighting cells or platelet transfusions in the past 7 days.
- Have a heart that pumps out at least 40% of its blood with each beat.
- If you could become pregnant, have a negative pregnancy test. Women who could become pregnant and men must use birth control or avoid sex during treatment and for 90 days afterward.
- Understand the study, sign a consent form, and still want to take part when treatment starts.
- Start treatment 45 to 90 days after transplant. At least 70% of the blood or bone marrow cells tested must come from the donor, with no signs of leukemia and blood counts and organ tests meeting study limits.
Who can't join
- Have had a previous stem cell transplant from a donor.
- Have AML that has returned or has not responded to treatment, based on a bone marrow test within 42 days before joining.
- Have had another cancer, unless you have been cancer-free for at least 5 years and the study doctor finds a low risk of return. Certain early cervical cancers and basal or squamous cell skin cancers are allowed.
- Have active hepatitis B or C, which are liver infections.
- Have severe heart failure, a history of poor heart pumping, dangerous heart rhythms, long-QT syndrome, or heart test results or other factors that raise the risk of dangerous rhythms.
- Have an uncontrolled illness that would prevent you from following study rules, or a severe infection when treatment starts. An infection throughout the body needing IV antibiotics within the prior 7 days also prevents starting.
- At treatment start, have acute graft-versus-host disease, when donor cells attack your body, needing prednisone-equivalent doses of at least 0.5 mg/kg/day within the prior week, or increased immune-suppressing treatment within the prior 2 weeks.
- Use an experimental drug that is not approved for any use while on the study.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: * Pathologically confirmed diagnosis of IDH1(R132)-mutant acute myeloid leukemia (AML). IDH1 mutations could have been detected by any mutational technique at any prior point including at diagnosis or remission. * Between the ages of 18 and 75 years * Will undergo allogeneic hematopoietic stem cell transplantation (HSCT) for their malignancy. Conditioning may be either conventional myeloablative (MAC) or reduced intensity conditioning (RIC). There will be no restrictions on type of graft source. * ECOG performance status ≤ 2 * Participants must have normal organ and marrow function as defined below: * Absolute neutrophil count ≥ 1000/µL without growth factor support (e.g. GCSF) in the previous 7 days. * Platelet count ≥ 50,000/µL without transfusional support in the previous 7 days. * AST (SGOT), ALT (SGPT) and Alkaline phosphatase \< 3x institutional upper limit of normal (ULN) * Direct bilirubin \< 2.0 mg/dL * Calculated creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula) * LVEF must be equal to or greater than 40%, as measured by MUGA scan or echocardiogram * Female patients of childbearing potential must have a negative pregnancy test * The effects of ivosidenib on the developing human fetus are unknown. For this reason female participants of child-bearing potential and male participants must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during the entire study treatment period and through 90 days after the last dose of treatment * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Prior allogeneic hematopoietic stem cell transplants. * Morphologically relapsed or refractory disease, as assessed by bone marrow aspirate and biopsy performed within 42 days prior to study entry * History of other malignancy(ies) unless * the participant has been disease-free for at least 5 years and is deemed by the investigator to be at low risk of recurrence of that malignancy, or * the only prior malignancy was cervical cancer in situ and/or basal cell or squamous cell carcinoma of the skin * Known diagnosis of active hepatitis B or hepatitis C * Current or history of congestive heart failure New York Heart Association (NHYA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (LVEF \< 40%, as measured by MUGA scan or echocardiogram) * Current or history of ventricular or life-threatening arrhythmias or diagnosis of long-QT syndrome * QTc interval (i.e., Friderica's correction \[QTcF\]) ≥ 450 ms or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) at screening * Uncontrolled intercurrent illness that would limit compliance with study requirements. Post-transplantation Pre-Treatment Criteria Treatment may begin at any time between day 45 and day 90 following stem cell transplantation. However, at time of treatment start, it must be ensured that: * The patient has continued willingness and interest in participating in the study. * There is no systemic infection requiring IV antibiotic therapy within 7 days preceding the first dose of study drug, or other severe infection * Chimerism studies reveal that ≥ 70% of blood or bone marrow cells, or of the CD33 expressing fraction, are of donor origin, * There is no acute graft versus host disease (GVHD), requiring an equivalent dose of ≥ 0.5mg/kg/day of prednisone within one week of starting ivosidenib / placebo, or have escalation of systemic immunosuppression in terms of increase of corticosteroids or addition of new agent/modality within two weeks of starting ivosidenib / placebo. * For prophylaxis for GVHD, agents that are permitted for administration on study: * Tacrolimus * Cyclosporine * Sirolimus * Cyclophosphamide * Mycophenolate Mofetil * Methotrexate * ATG * Ruxolitinib * Vedolizumab * As standards of care may change, any other prophylactic agents used should be discussed with the PI. * Investigational agents, defined as not approved for any indication, are forbidden unless the participant comes off study. * Agents used to treat GVHD that are permitted for administration on study: * Any agent used in prophylaxis may be continued (see list above) * Ruxolitinib * Etanarcept * ATG * Belumosidil * Axatilimab * Rituximab * Fecal microbiota transplantation * Alpha1-Antitrypsin * Pregnyl * Extracorporal photopheresis (ECP) * As standards of care may change, any other treatment agents used should be discussed with the PI. * Investigational agents, defined as not approved for any indication, are forbidden unless the participant comes off study. * There is no evidence of relapsed/recurrent/residual disease. * Prior to the start of ivosidenib / placebo administration, the participant must have adequate hematological function, defined as: * ANC ≥ 1000/µL * Platelets ≥ 50,000/µL and adequate organ function defined as * Direct bilirubin level \< 2.0 mg/dL * AST (SGOT), ALT (SGPT) and Alkaline phosphatase \< 3x institutional upper limit of normal (ULN) * No presence of congestive heart failure, defined by New York Heart Association (NHYA) criteria as class 3 or 4 * Calculated creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula)
Study sites (7)
GA
- Emory University Hospital · Atlanta, GA 30322Amelia Langston, MD · Study contact · 404-778-0519 · alangst@emory.eduAmelia Langston, MD · Principal investigatorMore trials in Atlanta
KS
- Kansas University Medical Center · Kansas City, KS 66160Sunil Abhyankar, MD · Study contact · 913-588-1227 · sabhyankar@kumc.eduSunil Abhyankar, MD · Principal investigatorMore trials in Kansas City
MA
- Massachusetts General Hospital · Boston, MA 02114Amir T Fathi, MD · Study contact · 617-724-1124 · afathi@mgh.harvard.eduAmir Fathi, MD · Principal investigatorMore trials in Boston
- Dana Farber Cancer Institute · Boston, MA 02115Robert Soiffer, MD · Study contact · 617-632-4731 · Robert_Soiffer@dfci.harvard.eduRobert Soiffer, MD · Principal investigatorMore trials in Boston
OH
- Ohio State University Wexner Medical Center- James Cancer Hospital · Columbus, OH 43210Jiasheng Wang, MD · Study contact · 614-293-3196 · jiasheng.wang@osumc.eduJiasheng Wang, MD · Principal investigatorMore trials in Columbus
UT
- Huntsman Cancer Institute, University of Utah · Salt Lake City, UT 84112Sagar Patel, MD · Study contact · 801-587-9014 · Sagar.Patel@hci.utah.eduSagar Patel, MD · Principal investigatorMore trials in Salt Lake City
WI
- Froedtert Hospital & the Medical College of Wisconsin · Milwaukee, WI 53226Sameem Abedin, MD · Study contact · 414-805-4600 · sabedin@mcw.eduSameem Abedin, MD · Principal investigatorMore trials in Milwaukee