SWOG clinical trial number
S1905

A Phase I/II Study of AKR1C3-Activated Prodrug OBI-3424 (OBI-3424) in Patients with Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL)/T-Cell Lymphoblastic Lymphoma (T-LBL)

Open
Phase
I-II
Accrual
0%
Abbreviated Title
A Phase I/II Study of AKR1C3-Activated Prodrug OBI-3424 (OBI-3424) in Patients with Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL)/T-Cell Lymphoblastic Lymphoma (T-LBL)
Status Notes
This study is open to accrual effective August 17, 2020 at 12:00 p.m. Pacific.
Activated
08/17/2020
Participants
ALLIANCE, ECOG-ACRIN, SWOG

Research committees

Leukemia
Lymphoma

Treatment

OBI-3424

Eligibility Criteria Expand/Collapse

Diagnosis of relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) based on WHO classification. Patients with relapsed T-cell lymphoblastic lymphoma are eligible if lymphoblasts are >/= 5% in the bone marrow or in the peripheral blood.

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.

Refractory to or have relapsed following a standard intensive chemotherapy regimen such as prior vincristine and prednisone or standard induction therapy.

A standard induction regimen is defined as any program of treatment that includes: (1) vincristine and corticosteroids plus at least one more chemotherapy agent, (2) cytarabine and anthracycline, or (3) high dose cytarabine.

No evidence of central nervous system disease within 28 days prior to registration. Patients with clinical signs or symptoms consistent with 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. Note that the patients may receive intrathecal chemotherapy with the initial lumbar puncture; see Section 7.1a.4.

Prior nelarabine therapy is not required. In addition, patients who do not receive 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.

Must not have had chemotherapy within 14 days prior to registration except for steroids, oral 6-mercaptopurine, oral methotrexate, vincristine, intrathecal chemotherapy, or hydroxyurea. See Section 7.3 for pre-treatment discontinuation instructions.

Must not have undergone allogeneic hematopoietic transplant within 90 days prior to registration.

No evidence of >/= Grade 2 acute graft versus host disease (GVHD) or moderate or severe limited chronic GVHD and must have no history of extensive GVHD of any severity within 90 days prior to registration. Patients posttransplant must be off calcineurin inhibitors for at least 28 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. See Section 18.4 for the Global severity scoring.

Must be >/= 18 years of age.

Must have a Zubrod Performance Status of 0‐3 (see Section 10.11).

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.

Must have creatinine clearance > 30 mL/min within 14 days prior to registration according to the Cockcroft Gault equation.

Must have direct bilirubin </= 1.5 x institutional upper limit of normal (ULN) within 14 days prior to registration.

Must have AST and ALT </= 3.0 x institutional ULN or </= 5.0 x ULN (if thought to be related to leukemic involvement) within 14 days prior to registration.

Must have the following tests within 14 days prior to registration to obtain baseline measurements. The results do not determine eligibility: PT/PTT/Fibrinogen (as clinically indicated); From Comprehensive Metabolic Panel: sodium, potassium, chloride, CO2, and BUN.

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.

Must not have a known history of prolonged QTcF (interval > 450 msec for males; > 470 msec for females).

Mmust 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.

Must agree to have bone marrow and blood specimens submitted for MRD testing as outlined in Section 15.2.

Must be offered the opportunity to participate in specimen banking. With patient consent, residuals from specimens submitted per Section 15.2 will be retained and banked for future research.

Reports & Approvals

Trial Locations