Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This phase II Pediatric MATCH trial studies how well ivosidenib works in treating patients
with solid tumors that have spread to other places in the body (advanced), lymphoma, or
histiocytic disorders that have IDH1 genetic alterations (mutations). Ivosidenib may block
the growth of cancer cells that have specific genetic changes in an important signaling
pathway called the IDH pathway.
Phase
Phase 2
Funding Agency/Sponsor
National Cooperative Group
Disease
Pediatric Cancer
Enrollment Eligibility
Inclusion Criteria:
- Patient must have enrolled onto APEC1621SC and must have been given a treatment
assignment to MATCH to APEC1621K based on the presence of an actionable mutation as
defined in APEC1621SC
- Patients must be >= than 12 months and =< 21 years of age at the time of study
enrollment
- Patients must have a body surface area >= 0.78 m^2 at enrollment
- Patients must be able to swallow intact tablets
- Patients must have radiographically measurable disease at the time of study
enrollment. Patients with neuroblastoma who do not have measurable disease but have
metaiodobenzylguanidine (MIBG)+ evaluable disease are eligible. Measurable disease in
patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one
dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
- Note: The following do not qualify as measurable disease:
- Malignant fluid collections (e.g., ascites, pleural effusions)
- Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
- Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
- Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
- Previously radiated lesions that have not demonstrated clear progression
post radiation
- Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16
years of age. Note: Neurologic deficits in patients with CNS tumors must have been
relatively stable for at least 7 days prior to study enrollment. Patients who are
unable to walk because of paralysis, but who are up in a wheelchair, will be
considered ambulatory for the purpose of assessing the performance score.
- Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy and must meet the following minimum duration from prior
anti-cancer directed therapy prior to enrollment. If after the required timeframe, the
numerical eligibility criteria are met, e.g. blood count criteria, the patient is
considered to have recovered adequately
- Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive.
>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42
days if prior nitrosourea)
- Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the
last dose of agent
- Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to grade =< 1
- Corticosteroids: If used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
- Hematopoietic growth factors: >= 14 days after the last dose of a long-acting
growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For
growth factors that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur. The duration of this interval must be discussed with
the study chair and the study-assigned research coordinator
- Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
- Stem cell infusions (with or without total body irradiation [TBI]):
- Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem
cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
>= 84 days after infusion and no evidence of graft versus host disease
(GVHD)
- Autologous stem cell infusion including boost infusion: >= 42 days
- Cellular Therapy: >= 42 days after the completion of any type of cellular therapy
(e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
- Radiation therapy (XRT)/external beam Irradiation including protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >=
50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
- Note: Radiation may not be delivered to "measurable disease" tumor site(s)
being used to follow response to subprotocol treatment
- Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days
after systemically administered radiopharmaceutical therapy
- Patients must not have received prior exposure to AG-120 (ivosidenib) or other
IDH1 inhibitors
- For patients with solid tumors without known bone marrow involvement: Peripheral
absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment)
- For patients with solid tumors without known bone marrow involvement: Platelet count
>= 100,000/mm^3 (transfusion independent, defined as not receiving platelet
transfusions for at least 7 days prior to enrollment)
- Patients with known bone marrow metastatic disease will be eligible for study provided
they meet the blood count (may receive transfusions provided they are not known to be
refractory to red cell or platelet transfusions). These patients will not be evaluable
for hematologic toxicity
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
ml/min/1.73 m^2 (within 7 days prior to enrollment), or
- A serum creatinine based on age/gender (within 7 days prior to enrollment)
- Age 1 to < 2 years, maximum serum creatinine (mg/dL) male 0.6, female 0.6
- Age 2 to < 6 years, maximum serum creatinine (mg/dL) male 0.8, female 0.8
- Age 6 to < 10 years, maximum serum creatinine (mg/dL) male 1, female 1
- Age 10 to < 13 years, maximum serum creatinine (mg/dL) male 1.2, female 1.2
- Age 13 to < 16 years, maximum serum creatinine (mg/dL) male 1.5, female 1.4
- Age >= 16 years, maximum serum creatinine (mg/dL) male 1.7, female 1.4
- Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
age (within 7 days prior to enrollment)
- Serum glutamate-pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L. (For the purpose of this study, the ULN for SGPT is 45 U/L) (within 7 days prior
to enrollment)
- Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
- Corrected QT (QTc )interval =< 450 milliseconds (within 7 days prior to enrollment)
- Note: Patients should avoid concomitant medication known or suspected to prolong
QTc interval or cause Torsades de Pointes. Patients who are receiving drugs that
prolong the QTc are eligible if the drug is necessary and no alternatives are
available
- Patients with seizure disorder may be enrolled if on anticonvulsants and well
controlled
- Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE]
version [v]5.0) resulting from prior therapy must be =< grade 2, with the exception of
decreased tendon reflex (DTR). Any grade of DTR is eligible
- All patients and/or their parents or legally authorized representatives must sign a
written informed consent. Assent, when appropriate, will be obtained according to
institutional guidelines
Exclusion Criteria:
- Pregnant or breast-feeding women will not be entered on this study due to risks
because there is yet no available information regarding human fetal or teratogenic
toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or
females of reproductive potential may not participate unless they have agreed to use
an effective non-hormonal contraceptive method for the duration of study treatment and
for at least 1 month after last dose of AG-120 (ivosidenib). Since AG-120 (ivosidenib)
may decrease concentrations of hormonal contraceptives, hormonal contraceptives are
not considered effective contraception when co-administered with AG-120 (ivosidenib)
- Patients receiving corticosteroids who have not been on a stable or decreasing dose of
corticosteroid for at least 7 days prior to enrollment are not eligible. If used to
modify immune adverse events related to prior therapy, >= 14 days must have elapsed
since last dose of corticosteroid
- Patients who are currently receiving another investigational drug are not eligible
- Patients who are currently receiving other anti-cancer agents are not eligible
- Patients who are receiving cyclosporine, tacrolimus or other agents to prevent
graft-versus-host disease post bone marrow transplant are not eligible for this trial
- Patients who are currently receiving drugs that are strong inducers or moderate to
strong inhibitors of CYP3A4 are not eligible. Strong inducers or moderate to strong
inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of
the study. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors
or metastases, on a stable dose, are allowed. In addition, patients receiving
sensitive or narrow therapeutic range substrates of CYP3A4 are not eligible
- Patients with a history of progressive multifocal leukoencephalopathy are not eligible
- Patients who have an uncontrolled infection are not eligible
- Patients who have received a prior solid organ transplantation are not eligible
- Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible