Clinical Trial - NCT03515512

IDH2 Inhibition Using Enasidenib as Maintenance Therapy for IDH2-mutant Myeloid Neoplasms Following Allogeneic Stem Cell Transplantation

Recruiting

Sponsor: Massachusetts General Hospital

Collaborators: Celgene

Information provided by (Responsible party): Principal Investigator Massachusetts General Hospital Amir Fathi Principal Investigator

ClinicalTrials.gov Identifier: NCT03515512

Protocol Info

Short Description: Phase I of Enasidenib as Maintenance for IDH2-mutant Myeloid Neoplasms Following ASCT
Long Description: A Phase I Study of IDH2 Inhibition Using Enasidenib as Maintenance Therapy for IDH2-mutant Myeloid Neoplasms Following Allogeneic Stem Cell Transplantation
MGH Status: Open
Sponsor: DF/HCC
Disease Program: BMT

Next Steps


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Purpose

This research study is studying a targeted therapy drug as a possible treatment for IDH2 mutant acute myeloid leukemia or chronic myelomonocytic leukemia while undergoing hematopoietic stem cell transplantation. The drug involved in this study is: -Enasidenib.
Condition Title Intervention Phase
Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia Enasidenib Phase 1
Study Type Interventional
Official Title A Phase I Study of IDH2 Inhibition Using Enasidenib as Maintenance Therapy for IDH2-mutant Myeloid Neoplasms Following Allogeneic Stem Cell Transplantation

Primary Outcome Measures

Maximum Tolerated Dose (MTD) [Time Frame: 28 Days] [Designated as safety issue: ]

Number of participants with dose limiting toxicities (DLT) [Time Frame: 28 days] [Designated as safety issue: ]


Secondary Outcome Measures

The number of participants with Enasidenib related adverse events [Time Frame: From the start of treatment until 30 days after the end of treatment, treatment may continue for up to 12 28-day cycles] [Designated as safety issue: ]

Cumulative incidence of acute GVHD [Time Frame: Cycle 1 days 1, 8, and 15; day 1 of every subsequent cycle (cycles are 28-days), up to 100 days after the start of treatment] [Designated as safety issue: ]

Cumulative incidence of chronic GVHD [Time Frame: Cycle 1 days 1, 8, and 15; Day 1 of cycles 2-12 (1 cycle is 28-days), up to 1 year of total follow-up] [Designated as safety issue: ]

Plasma and marrow 2-hydroxyglutarate levels [Time Frame: Screening, cycle 1 days 8 and 15, day 1 of cycles 2 and 3, at the time of relapse, up to one year total follow-up] [Designated as safety issue: ]

IDH clonal evolution via whole genome sequencing [Time Frame: Screening, cycle 1 days 8 and 15, day 1 of cycles 2 and 3, at the time of relapse, up to one year total follow-up] [Designated as safety issue: ]

IDH Mutational burden via next-generation sequencing [Time Frame: Screening, cycle 1 days 8 and 15, day 1 of cycles 2 and 3, at the time of relapse, up to one year total follow-up] [Designated as safety issue: ]

Estimated Enrollment: 22
Study Start Date: July 2018
Estimated Study Completion Date: May 2024
Estimated Primary Completion Date: May 2021
Arms Assigned Interventions

Experimental:Enasidenib

Enasidenib will be administered orally once daily in 28-day cycles
Drug:Enasidenib
Enasidenib may help block the over production of IDH2, which when mutated, can overproduce metabolites and compounds that contribute to the growth of tumors and cancerous cells

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Pathologically confirmed diagnosis of IDH2-mutant acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML).
  • IDH2 mutations will include any IDH2 R140 or R172 alterations
  • Eligibility and enrollment will be based on local IDH2 mutational testing performed at any center. The presence of an IDH2 mutation at the time of initial diagnosis or any other time thereafter is necessary and sufficient. The presence of an IDH2 mutation at time of enrollment is not necessary for the purposes of eligibility.
  • Between the ages of 18 and 75 years
  • Will undergo first allogeneic hematopoietic stem cell transplantation (HSCT) for their malignancy. Conditioning may have been either conventional myeloablative (MAC) or reduced intensity conditioning (RIC).
  • HSCT Donor will be one of the following:
  • 5/6 or 6/6 (HLA-A, B, DR) matched related donor
  • 7/8 or 8/8 (HLA-A, B, DR, C) matched unrelated donor. Matching in the unrelated setting must be at the allele level.
  • Haploidentical related donor, defined as ≥ 3/6 (HLA-A, B, DR) matched --≥ 4/6 (HLA-A, B, DR) umbilical cord blood (UCB). Matching in the UCB setting is at the antigen level. Recipients may receive either one or two UCB units. In the case of 2 UCB units, both units must have been at least 4/6 matched with the recipient.
  • 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 50%, as measured by MUGA scan or echocardiogram
  • Female patients of childbearing potential must have a negative pregnancy test, as measured by serum or urine testing
  • The effects of enasidenib on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during the entire study treatment period and through 6 months 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.
  • Evidence of relapsed/recurrent/residual 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 < 50%, as measured by MUGA scan or echocardiogram)
  • Current or history of ventricular or life-threatening arrhythmias or diagnosis of long-QT syndrome
  • Systemic infection requiring IV antibiotic or antifungal or antiviral therapy within 7 days preceding the first dose of study drug, or other severe infection
  • Known dysphagia, short-gut syndrome, gastroparesis, or other condition(s) that limits the ingestion or gastrointestinal absorption of drugs administered orally
  • Uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or diastolic BP > 100 mmHg)
  • 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
  • Concomitant receipt of the following sensitive CYP substrate medications that have a narrow therapeutic range (unless the participant can be transferred to other medications at least 5 half-lives prior to the start of study treatment): paclitaxel and docetaxel (CYP2C8), phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline, and tizanidine (CYP1A2)
  • Concomitant receipt of the breast cancer resistance protein (BCRP) transporter-sensitive substrate rosuvastain (unless the participant can be transferred to another medication at least 5 half-lives prior to the start of study treatment)
  • Uncontrolled intercurrent illness that would limit compliance with study requirements.
  • HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with study drug. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03515512

Locations

  • United States, Maryland
    • Johns Hopkins Cancer Center Baltimore, Maryland, United States, 21287
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02214
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Ohio
    • Ohio State University Comprehensive Cancer Center Columbus, Ohio, United States, 43210

Sponsors and Collaborators

Massachusetts General Hospital

Celgene

More Information

No publications provided

Responsible Party: Principal Investigator Massachusetts General Hospital Amir Fathi Principal Investigator
ClinicalTrials.gov Identifier: NCT03515512
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Massachusetts General Hospital:

Acute Myeloid Leukemia

Chronic Myelomonocytic Leukemia

Additional relevant MeSH terms:

Leukemia

Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Myelomonocytic, Acute

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on July 18, 2019