Inclusion Criteria:
- - PRE-REGISTRATION: Age ≥ 18 years.
- - PRE-REGISTRATION: Not eligible for or have failed therapies with established
benefits, at the discretion of the treating physician.
- - PRE-REGISTRATION: Patients must meet one of the following criteria:
- Relapsed/refractory patients with Erdheim-Chester disease, Langerhans
histiocytosis, histiocytic sarcoma, or other malignant histiocytosis without
activating alterations in v-Raf murine sarcoma viral oncogene homolog B (BRAF)
or Mitogen-activated protein kinase kinase (MAP2K) oncogenes who have
progressed after first line of therapy.
- - Note: Relapsed is defined as a relapse that occurred after having a
response to the last therapy at any point during the treatment.
Refractory
is no response (stable disease or progressive disease while on therapy) to
a given treatment at least after 1 month of being on the given treatment.
- - Newly diagnosed patients with Rosai-Dorfman disease without activating
alterations in MAP2K oncogenes.
- - Relapsed/refractory patients with Rosai-Dorfman disease and an activating
mitogen-activated protein kinase (MAPK) pathway alteration who have failed
prior treatment with cobimetinib.
- - Relapsed/refractory patients with Erdheim-Chester disease or Langerhans
histiocytosis who have received vemurafenib for BRAF V600E mutated disease or
cobimetinib for disease with activating MAP2K alterations.
- - Patients with Erdheim-Chester disease, Rosai-Dorfman disease, Langerhans
histiocytosis, histiocytic sarcoma, or another malignant histiocytosis who
cannot tolerate or have a contraindication to BRAF or MEK inhibitors or those
who cannot have reliable access to these inhibitors due to financial restraints
or geographic location or initiation of BRAF or mitogen-activated protein
kinase kinase (MEK) inhibitors is futile based on the genomic alterations or
the discretion of treating physician.
- - Relapsed/refractory higher risk myelodysplastic syndromes (MDS), chronic
myelomonocytic leukemia (CMML) or primary myelofibrosis (PMF).
- - Note: PMF patients must have failed ≥ 1 of the 4 Food and Drug
Administration (FDA)-approved Janus kinase (JAK) Inhibitors for MF (i.e.
ruxolitinib, fedratinib, pacritinib, momelotinib) to be eligible.
MDS and
CMML patients must have failed hypomethylating agent-based therapy, if
eligible.
- - Note: Higher risk is defined as intermediate or higher risk by
international prognostic scoring system (IPSS-R) or moderate high or
higher risk as per molecular internal prognostic scoring system (IPSS-M).
- - T cell lymphoma (peripheral and cutaneous), or mantle cell lymphomas.
Patients
must have failed ≥ 2 lines of therapy.
- - Primary central nervous system (CNS) lymphoma who has failed ≥ 2 lines of
therapy.
- - Relapsed or refractory follicular lymphoma; or Waldenstrom
macroglobulinemia/lymphoplasmacytic lymphoma.
Must have failed ≥ 2 lines of
therapy.
- - Patients with Waldenström macroglobulinemia who have received or are not
eligible for a Bruton tyrosine kinase (BTK)-inhibitor therapy.
- - Relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic
lymphoma (SLL) who have failed ≥ 2 lines of therapy and have been treated with
at least one prior line of a BTK inhibitor and/or a B-cell lymphoma 2 (BCL2)
inhibitor.
Need documented CLL/SLL requiring treatment according to
International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines 2018.
- - NOTE: Use of oral steroids up to 20 mg of daily will be allowed for
patients who are discontinuing BTK inhibitors just prior to the
registration.
This is not mandatory and should be done at the discretion
of patient's treating physician.
- - Note: All patients in the above disease groups may be on
corticosteroids at the investigator's discretion.
- - PRE-REGISTRATION: Histopathological or cytological confirmation of diseases.
- - PRE-REGISTRATION: Willingness to provide mandatory blood, bone marrow aspirate,
saliva, and tissue specimens for correlative research, as applicable to the disease
site.
- - PRE-REGISTRATION: Ability to swallow pills.
- - REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0,
1, or 2.
- - REGISTRATION: Life expectancy of ≥ 3 months.
- - REGISTRATION: Measurable or assessable disease:
- For histiocytic neoplasms and lymphoma-measurable disease is defined as
measurable by CT (dedicated CT or the CT portion of a PET/CT) or MRI: To be
considered measurable, there must be at least one lesion that has a single
diameter of ≥ 1.5 cm for non-CNS disease.
For CNS involved disease, MRI
confirmation with any size would be appropriate.
- - NOTE: Skin lesions can be used if the area is ≥ 1.5 cm in at least one
diameter and photographed with a ruler.
Patients with assessable disease
by PET/CT are also eligible as long as the assessable disease is biopsy
proven lymphoma or histiocytic/dendritic cell neoplasms.
- - For all other eligible diseases listed-N/A.
- - REGISTRATION: Hemoglobin ≥ 8.0 g/dL (obtained ≤ 14 days prior to registration)
- REGISTRATION: Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L (obtained ≤ 14 days
prior to registration)
- REGISTRATION: Platelet count ≥ 80 x 10^9/L (obtained ≤ 14 days prior to
registration)
- REGISTRATION: White blood cell (WBC) ≥ 2.5 x 10^9/L (obtained ≤ 14 days prior to
registration)
- REGISTRATION: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 14
days prior to registration)
- REGISTRATION: Alanine aminotransferase (ALT), aspartate transaminase (AST), and
alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver
involvement) (obtained ≤ 14 days prior to registration)
- REGISTRATION: Serum creatinine of ≤ 1.5 x ULN and calculated creatinine clearance of
≥ 50 mL/min using the Cockcroft-Gault formula (obtained ≤ 14 days prior to
registration)
- REGISTRATION: Negative urine or serum pregnancy test done ≤ 7 days prior to
registration, for persons of childbearing potential only.
- - REGISTRATION: Sexually active patients and their partners must use an effective
method of contraception associated with a low failure rate prior to study entry and
for the duration of study participation and for at least 3 months after the last
dose of study drug.
- - Note: The following are considered effective contraceptives: oral contraceptive
pill; condom plus spermicide; diaphragm plus spermicide; patient or partner
surgically sterile; patient or partner more than 2 years postmenopausal; or
injectable or implantable agent/device.
- - REGISTRATION: Provide written informed consent.
- - REGISTRATION: Ability to complete questionnaire(s) by themselves or with assistance.
- - REGISTRATION: Willing to return to the enrolling institution for follow-up (during
the Active Monitoring Phase of the study).
Exclusion Criteria:
- - PRE-REGISTRATION: Myeloproliferative neoplasm (MPN) patients with known active CNS
metastases and/or carcinomatous meningitis.
- - Note: Histiocytosis and lymphoma patients who are on steroids are allowed to
enroll.
- - REGISTRATION: Any of the following because this study involves an investigational
agent whose genotoxic, mutagenic and teratogenic effect on the developing fetus and
newborn are unknown:
- Pregnant persons.
- - Persons of childbearing potential (and persons able to father a child) who are
unwilling to employ adequate contraception.
- - REGISTRATION: New York Heart Association Class III or IV cardiac disease, or
myocardial infarction, severe unstable angina, coronary/peripheral artery bypass
graft, congestive heart failure ≤ 6 months prior to registration.
- - REGISTRATION: Corrected QT interval (using Fridericia's correction formula) (QTcF)
of > 470 msec.
- - REGISTRATION: Known active infection with human immunodeficiency virus (HIV), Human
T-lymphotropic virus 1 (HTLV-1), hepatitis B virus (HBV), or hepatitis C virus
(HCV):
- Active infection with (HIV) and CD4+ T-cell count < 350 μL.
- - Patients with a detectable HIV viral load and not on antiretroviral therapy
(ART) for ≥ 4 weeks.
- - Exceptions:
- Patients with a history of hepatitis B or C are allowed if HBV
deoxyribonucleic acid (DNA) or HCV ribonucleic acid (RNA) are
undetectable.
- - Patients with active HIV infection and CD4+ T-cell count ≥ 350 μL who are
on active antiretroviral treatment.
- - REGISTRATION: Active, uncontrolled bacterial, viral, or fungal infections, requiring
systemic therapy.
- - REGISTRATION: Concomitant use of strong inhibitors and inducers of CYP1A2, CYP2C19,
CYP2D6, and strong inhibitors and inducers of CYP3A4 within five half-lives of the
active drug prior to registration and throughout the trial.
- - Note: Strong inhibitors and inducers of CYP3A4 should be discontinued for five
half-lives of the active drug prior to starting study drug and avoided
throughout the trial.
- - REGISTRATION: Concomitant use of any herbal supplements.
- - Note: Supplements taken prior to starting study drug should be discussed with
the Principal Investigator as varied washout periods may be clinically
indicated and necessary.
- - REGISTRATION: Any of the following prior therapies used as primary cancer treatment:
- Targeted therapeutics other than monoclonal antibodies (e.g., kinases
inhibitors) ≤ 2 weeks prior to registration.
- - Monoclonal antibodies ≤ 6 weeks, or ≥ 5 half-life, whichever is shorter, prior
to registration.
- - Chemotherapy ≤ 4 weeks prior to registration (6 weeks for nitrosoureas or
Mitomycin C.
- - Surgery ≤ 4 weeks prior to registration.
- - Any investigational therapy ≤ 4 weeks prior to registration.
- - Radiation therapy ≤ 4 weeks prior to registration.
- - Exceptions:
- Palliative radiation therapy ≥ 2 weeks prior to registration for
control of tumor mass related symptoms (e.g., pain control from a
discrete bone metastasis) allowed, unless the radiation field
includes organs for which the radiation therapy could result in
certain direct organ toxicities (e.g., radiation induced
esophagitis), which could complicate the interpretation of the Q702
safety profile.
- - Radiation induced toxicities which could interfere with the
interpretation of the Q702 safety profile should recover to ≤ grade 1
before registration.
- - Patients receiving palliative radiation intended to reduce the risk
of a potential pathological fracture should be allowed ≥ 4 weeks from
the last radiation therapy treatment to recover from any radiation
induced toxicity and to allow for an adequate period of observation
relative to the potential risk of a pathological fracture.
- - REGISTRATION: Failure to recover from acute, reversible effects of prior therapy to
≤ grade 1 or patient baseline prior to registration.
- - NOTE: Patient with chronic effects such as neuropathy, fatigue,
keratitis/keratopathy, anorexia, etc. are allowed.
- - REGISTRATION: Co-morbid systemic illnesses or other severe concurrent disease which,
in the judgment of the investigator, would make the patient inappropriate for entry
into this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens.
- - REGISTRATION: Active retinal pigment epithelium (RPE)/photoreceptor disorders such
as retinitis pigmentosa, cone-rod dystrophies, Bests dystrophy, Stargardt disease
(STGD), macular degeneration, retinal detachment, and opaque cornea.
Exceptions:
- - Mild blurry vision, either age-related or due to ocular or systemic disorder
(e.g., diabetes, dry eyes, cataracts, uncorrected refraction abnormality) may
be allowed at the discretion of the ophthalmologist if deemed as not
constituting evidence of pre-existing retinopathy (e.g., severe
nonproliferative or proliferative diabetes retinopathy) or a condition with the
potential to cause a predisposition to drug-induced retinopathy.
[e.g., severe
retinal vascular disease with scattered intraretinal hemorrhages, cotton
wool-spots and intraretinal microvascular abnormalities (IRMA)]
- - Patients with only one assessable eye and no evidence of pre-existing
retinopathy may be allowed at the discretion of the principal investigator.
- REGISTRATION: Active second malignancy requiring treatment that would interfere with
the assessment of the response of the primary cancer or interpretation of the safety
of this protocol therapy
