Trial Title:
Olutasidenib for the Treatment of Patients With IDH1 Mutated AML, MDS or CMML After Donor Hematopoietic Cell Transplant
NCT ID:
NCT06543381
Condition:
Acute Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Myelodysplastic Syndrome
Conditions: Official terms:
Leukemia
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (olutasidenib)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Olutasidenib
Description:
Given PO
Arm group label:
Treatment (olutasidenib)
Other name:
FT 2102
Other name:
FT-2102
Other name:
FT2102
Other name:
IDH1-R132 Inhibitor FT-2102
Other name:
Rezlidhia
Summary:
This phase I trial tests the safety, side effects, and effectiveness of olutasidenib in
preventing the return of disease (relapse) in patients who have undergone donor
(allogeneic) hematopoietic cell transplant for acute myeloid leukemia (AML),
myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML) carrying an
IDH1 mutation. Olutasidenib is in a class of medications called IDH1 inhibitors. It works
by slowing or stopping the growth of cancer cells. Giving olutasidenib may be safe,
tolerable and/or effective in preventing relapse in patients with IDH1 mutated AML, MDS
or CMML after an allogeneic hematopoietic cell transplant.
Detailed description:
PRIMARY OBJECTIVE:
I. Evaluate the safety and tolerability of olutasidenib as maintenance therapy after
allogeneic hematopoietic cell transplantation (HCT) in patients with IDH1-mutated acute
myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic
leukemia (CMML).
SECONDARY OBJECTIVES:
I. Assess overall survival (OS) and leukemia-free survival (LFS) at 1 and 2 years after
first dose of olutasidenib.
II. Estimate cumulative incidence of relapse (CIR), non-relapse mortality (NRM),
graft-versus-host disease (GVHD) free, relapse-free survival (GRFS) at 1 and 2 years
after first dose of olutasidenib.
III. Rate and grading of acute GVHD of grades 2-4 and 3-4 at day 100 post allogeneic HCT.
IV. Incidence and grading of chronic GVHD of all grades at 1 and 2 years after first dose
of olutasidenib.
EXPLORATORY OBJECTIVES:
I. Monitor disease status by multiparameter flow cytometry among a subset of patients
with minimal residual disease (MRD)+ disease when starting olutasidenib.
II. Molecular monitoring of disease status by HopeSeq complete (at City of Hope [COH])
and equivalent next generation sequencing (NGS) assay at Cleveland Clinic.
III. Monitor immune reconstitution by flow cytometry during protocol therapy. IV. Mutant
(m)IDH1 testing on peripheral blood samples with standard polymerase chain reaction
(PCR).
V. Investigate IFN-ɣ signaling in immune cell subsets before and during maintenance
therapy.
VI. Monitor mIDH1 variant allele fraction (VAF) by droplet digital PCR (ddPCR) beads,
emulsion, amplification, magnetics (BEAM)ing technology on peripheral blood.
OUTLINE:
Starting 50-120 days after bone marrow transplant, patients receive olutasidenib orally
(PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days for up to
24 cycles in the absence of disease progression or unacceptable toxicity. Patients also
undergo blood sample collection on study.
After completion of study treatment, patients are followed up at 30 days and then up to 2
years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Documented informed consent of the participant and/or legally authorized
representative
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If
unavailable, exceptions may be granted with study principal investigator (PI)
approval
- Age: ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) ≤ 2 or Karnofsky performance status (KPS)
≥ 70
- Patients who are scheduled to receive or have already undergone allogeneic
hematopoietic cell transplantation (alloHCT) from any donor type, any conditioning
regimen, and regardless of GVHD prophylaxis will be include
- Patients must have AML, MDS, or CMML with mIDH1 diagnosis at diagnosis (regardless
of time from HCT). Note: Patient with pre-HCT disease relapse will no be included if
mIDH1 is not detected after relapse
- Day 30 marrow post alloHCT should show evidence of morphologic remission with < 5%
bone marrow (BM) blasts. Patients with MRD-positive status either by flow cytometry
or IDH1 mutation testing will be eligible
- Patients with previous therapy with IDH1 inhibitors will be included
- Absolute neutrophil count (ANC) > 1000/mm^3 (within 28 days prior to day 1 of
protocol)
- Hemoglobin ≥ 8.0 gm/dL (within 28 days prior to day 1 of protocol)
- Platelets ≥ 50,000/mm^3 (within 28 days prior to day 1 of protocol) Note: Patients
with lower counts can enroll if infection cytomegalovirus (CMV)/human herpes virus 6
(HHV6), etc. is being treated actively
- Bilirubin ≤ 2 x upper limit of normal (ULN) (within 28 days prior to day 1 of
protocol) (unless has Gilbert's disease). Patients with abnormal liver function
tests (LFTs) due to active GVHD will not be eligible
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT])
≤ 2 x ULN (within 28 days prior to day 1 of protocol). Patients with abnormal LFTs
due to active GVHD will not be eligible
- Creatinine clearance of ≥ 30/min/1.73 m^2 for participants with creatinine levels
above institutional normal per 24 hour urine test or the Cockcroft-Gault formula
(within 28 days prior to day 1 of protocol)
- Corrected QT interval (QTc) ≤ 480 ms (Note: To be performed within 28 days prior to
day 1 of protocol therapy)
- Seronegative for HIV antigen/antibody (Ag/Ab) combo, hepatitis C virus (HCV) (if
positive, hepatitis C ribonucleic acid [RNA] quantitation must be performed), active
hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma
reagin [RPR]) (within 28 days prior to day 1 of protocol)
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
(within 28 days prior to day 1 of protocol). If the urine test is positive or cannot
be confirmed as negative, a serum pregnancy test will be required
- Agreement by females and males of childbearing potential, defined as not being
surgically sterilized (men and women) or have not been free from menses for > 1 year
(women only), to use an effective method of birth control or abstain from
heterosexual activity for the course of the study through at least 3 months after
the last dose of protocol therapy
Exclusion Criteria:
- Patients with more than one allogeneic HCT
- History of allergic reactions attributed to compounds of similar chemical or
biological composition to study agent
- Active diarrhea considered clinically significant and may impair oral drug
administration
- Clinically significant uncontrolled illness
- Uncontrolled infection requiring systemic antimicrobials
- Active infection: Patients with treated viral, bacterial or fungal infections
that are controlled on therapy will be allowed to participate
- Participant has detectable human immunodeficiency virus (HIV) viral load within the
previous 6 months (must have viral load testing prior to study enrollment if
participant has a known history of HIV 1/2 antibodies)
- Active hepatitis B or C, or HIV
- Other active malignancy. Participants with history of prior malignancy treated with
curative intent who achieved CR more than 2 years before study entry are eligible.
This exclusion rule does not apply to non-melanoma skin tumors and in-situ cervical
cancer
- Females only: Pregnant or breastfeeding
- Active grade II-IV acute GVHD per Mount Sinai Acute Graft Versus Host Disease
International Consortium (MAGIC) criteria and/or requiring systemic steroids with
prednisone dose equivalent of ≥ 0.25 mg/kg at end of 4 weeks. Patients with a mild
form of acute GVHD involving skin, gut or liver requiring topical steroid creams or
oral beclomethasone (8 mg/day), entocort, (9 mg/day) and/or solumedrol (and
equivalent prednisone) will be allowed
- Any other condition that would, in the investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to
comply with all study procedures (including compliance issues related to
feasibility/logistics)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amandeep Salhotra
Phone:
626-218-2405
Email:
asalhotra@coh.org
Investigator:
Last name:
Amandeep Salhotra
Email:
Principal Investigator
Facility:
Name:
Cleveland Clinic Cancer Center
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Abhay Singh, MD, MPH
Phone:
866-320-4573
Email:
singha21@ccf.org
Investigator:
Last name:
Abhay Singh, MD, MPH
Email:
Principal Investigator
Start date:
December 15, 2024
Completion date:
February 5, 2027
Lead sponsor:
Agency:
City of Hope Medical Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
City of Hope Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06543381
