UT Health San Antonio

Eligibility

Eligible Ages

Over 12 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

Criteria

Inclusion Criteria:

- Patients must have a diagnosis of relapsed or refractory T-cell acute lymphoblastic
leukemia (T-ALL) based on World Health Organization (WHO) classification. Patients
with relapsed/refractory T-cell lymphoblastic lymphoma are eligible if lymphoblasts
are >= 5% in the bone marrow or in the peripheral blood by morphology or flow
cytometry

- Patients must have evidence of acute leukemia in their peripheral blood or bone
marrow. Patients must have >= 5% lymphoblasts in the peripheral blood or bone marrow
within 14 days prior to registration. Patients with only extramedullary disease are
not eligible

- Patients ≥ 18 years of age must be refractory to or have relapsed following a
standard induction chemotherapy. Patients < 18 years of age must have relapsed or
must be refractory after 2 or more chemotherapy cycles (example: induction and
consolidation)

- A standard chemotherapy induction regimen is defined as any program of
treatment that includes:

- Vincristine and corticosteroids plus at least one more chemotherapy agent

- Cytarabine and anthracycline, or

- High dose cytarabine (defined as at least 1 gr/m^2 per individual dose
unless adjustments were required for renal/liver function)

- Patients must have no evidence of central nervous system disease within 28 days
prior to registration based on cerebrospinal fluid (CSF) studies. Patients with
clinical signs or symptoms consistent with central nervous system (CNS) involvement
must have a lumbar puncture which is negative for CNS involvement; the lumbar
puncture must be completed within 28 days prior to registration. Patients with CNS1
or CNS2 are eligible; however patients with CNS3 are not eligible

- Note that the patients may receive intrathecal chemotherapy with the initial lumbar
puncture. This may count as the first dose of intrathecal therapy required as part
of the study

- Prior nelarabine therapy is not required. In addition, for patients ≥ 18 years of
age who received nelarabine during initial induction or post-remission treatment are
eligible only if the physician does not feel they would benefit from other,
multi-agent chemotherapy

- Patients must not have had chemotherapy or investigational agents within 14 days
prior to registration except for corticosteroids, oral 6-mercaptopurine, oral
methotrexate, vincristine, intrathecal chemotherapy, or hydroxyurea. For
participants who have received radiation therapy, at least 7 days must have elapsed
from the end of radiation prior to registration and participants must not currently
be experiencing toxicities from radiation therapy

- Patients must not have undergone allogeneic hematopoietic transplant within 90 days
prior to registration

- Patients must have no evidence of active >= grade 2 acute graft versus host disease
(GVHD) or moderate or severe limited chronic GVHD. Patients must have no history of
extensive GVHD of any severity within 90 days prior to registration. Patients who
are post-transplant must be off calcineurin inhibitors for at least 21 days to be
eligible. Extensive GVHD is defined as 1) generalized skin involvement or 2)
localized skin involvement and/or hepatic dysfunction plus liver histology or
cirrhosis or involvement of eye or minor salivary organ or oral mucosa or any other
target organ

- Patients must be >= 12 years of age

- Patients ≥ 16 years of age must have a Zubrod Performance Status of 0-3. Patients <
16 years of age must have a Lansky score of ≥ 50

- Patients must not have systemic fungal, bacterial, viral or other infection that is
not controlled (defined as exhibiting ongoing signs/symptoms related to the
infection and without improvement, despite appropriate antibiotics or other
treatment) within 14 days prior to registration

- Patients ≥ 18 years of age must have creatinine clearance > 30 mL/min within 14 days
prior to registration according to the Cockcroft Gault equation

- Patients 12-17 years of age must have adequate renal function within 14 days prior
to registration defined as serum creatinine ≤ 1.5 x institutional upper limit of
normal (ULN) according to age or a calculated estimated glomerular filtration rate
(eGFR) (based on Schwartz formula) or radioisotope glomerular filtration rate (GFR)
≥ 50ml/min/1.73 m^2

- Patients must have direct bilirubin =< 1.5 x institutional upper limit of normal
(ULN) within 14 days prior to registration

- Patients must have alanine aminotransferase (ALT) =< 3.0 x institutional upper limit
of normal (ULN) or =< 5.0 x ULN (if thought to be related to leukemic involvement)
within 14 days prior to registration

- Prothrombin time (PT)/partial thromboplastin time (PTT)/ fibrinogen (as clinically
indicated for example but not limited to history of bleeding or active bleeding,
concern for disseminated intravascular coagulation) (within 14 days prior to
registration to obtain baseline measurements)

- From metabolic panel (comprehensive or basic): sodium, potassium, chloride, carbon
dioxide (CO2), and blood urea nitrogen (BUN) (within 14 days prior to registration
to obtain baseline measurements)

- Patients must be able to safely discontinue use of strong inhibitors/inducers of
CYP3A4 or PgP-g-p and must be able to safely discontinue use of naproxen for 48
hours before and after each dose of OBI-3424

- Patients with known human immunodeficiency virus (HIV)-infection are eligible
providing they are on effective anti-retroviral therapy and have undetectable viral
load at their most recent viral load test within 6 months prior to registration.
(HIV viral load testing is required only for patients with known HIV infection).
Patients must not be receiving antiviral therapies that are known strong inhibitors
or inducers of CYP3A4

- Patients with evidence of chronic hepatitis B virus (HBV) infection may be eligible
provided that they have an undetectable HBV viral load within 28 days prior to
registration. Patients may be currently receiving HBV treatment. (HBV viral load
testing is required only for patients with known HBV infection). Patients must not
be receiving antiviral therapies that are known strong inhibitors or inducers of
CYP3A4

- Patients with known history of hepatitis C virus (HCV) infection may be eligible
provided that they have an undetectable HCV viral load within in 28 days prior to
registration. Patients may be currently receiving treatment. (HCV viral load testing
is required only for patients with known HCV infection). Patients must not be
receiving antiviral therapies that are known strong inhibitors or inducers of CYP3A4

- Patients must not have a known history of prolonged QT interval by Fridericia (QTcF)
(interval > 450 msec for males; > 470 msec for females). Patients that had transient
prolongation of QTc secondary to medications or electrolyte abnormalities are not
excluded if the QTc normalized and remain within acceptable QTcF range (interval >
450 msec for males; > 470 msec for females). Additionally, suspected medications
should be no longer required or used, and electrolyte abnormalities must have
normalized

- Patients must not be pregnant or nursing due to the teratogenic potential of the
drug used on this study. Females of reproductive potential must have a negative
serum pregnancy test within 14 days prior to registration. Women/men of reproductive
potential must have agreed to use an effective contraceptive method during and up to
6 months after treatment. A woman is considered to be of "reproductive potential" if
she has had menses at any time in the preceding 12 consecutive months. In addition
to routine contraceptive methods, "effective contraception" also includes
heterosexual celibacy and surgery intended to prevent pregnancy (or with a
side-effect of pregnancy prevention) defined as a hysterectomy, bilateral
oophorectomy or bilateral tubal ligation. However, if at any point a previously
celibate patient chooses to become heterosexually active during the time period for
use of contraceptive measures outlined in the protocol, he/she is responsible for
beginning contraceptive measures

- Patients must not have other active malignancies for which they have received
treatments within 6 months prior to registration excluding localized malignancies
that do not require systemic treatment

- Patients must agree to have bone marrow and blood specimens submitted for MRD
testing

- Patients must be offered the opportunity to participate in specimen banking. With
patient consent, residuals from specimens submitted will be retained and banked for
future research

- Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with fedral, local, institutional
and Central Institutional Review Board (CIRB) guidelines unless they are unable to
provide consent based on age (< 18 years) or based on impaired decision-making
capabilities. For patients < 18 years of age or with impaired decision making
capabilities, parents or other legally authorized representatives must sign and give
informed consent on behalf of study participants in accordance with applicable
federal, local, institutional and CIRB regulations

- As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has
been entered in the system

- This trial will use a slot reservation system to enroll the Phase I portion of the
study. Patients planning to enroll at this phase of the study must first have a slot
reserved in advance of the registration. All site staff will use OPEN to create a
slot reservation