Clinical Trials /

Study to Test AKR1C3-Activated Prodrug OBI-3424 (OBI-3424) in Patients With Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL)

NCT04315324

Description:

This phase II trial studies how well OBI-3424 works in treating patients with T-cell acute lymphoblastic leukemia that has come back (relapsed) or does not response to treatment (refractory). Drugs used in chemotherapy, such as OBI-3424, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. OBI-3424 may reduce the amount of leukemia in the body.

Related Conditions:
  • T-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Test AKR1C3-Activated Prodrug OBI-3424 (OBI-3424) in Patients With Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL)
  • Official Title: A Phase II Study of AKR1C3-Activated Prodrug OBI-3424 (OBI-3424) in Patients With Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL)

Clinical Trial IDs

  • ORG STUDY ID: S1905
  • SECONDARY ID: NCI-2020-00768
  • SECONDARY ID: S1905
  • SECONDARY ID: S1905
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT04315324

Conditions

  • Recurrent T Acute Lymphoblastic Leukemia
  • Refractory T Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
AKR1C3-activated Prodrug OBI-3424AKR1C3-activated Prodrug TH-3424, Aldo-keto Reductase 1c3-activated Prodrug OBI-3424, OBI 3424, OBI-3424, OBI3424, TH 3424, TH-3424, TH3424Treatment (AKR1C3-activated prodrug OBI-3424)

Purpose

This phase II trial studies how well OBI-3424 works in treating patients with T-cell acute lymphoblastic leukemia that has come back (relapsed) or does not response to treatment (refractory). Drugs used in chemotherapy, such as OBI-3424, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. OBI-3424 may reduce the amount of leukemia in the body.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To assess the response rate (complete remission [CR] or CR with incomplete count recovery
      [CRi]) of AKR1C3-activated prodrug OBI-3424 (OBI-3424) in patients with relapsed/refractory
      T-cell acute lymphoblastic leukemia (T-ALL).

      SECONDARY OBJECTIVES:

      I. To estimate the frequency and severity of toxicities of OBI-3424 in this patient
      population.

      II. To estimate event-free survival (EFS), relapse-free survival (RFS) and overall survival
      (OS) in this patient population.

      TRANSLATIONAL MEDICINE OBJECTIVES:

      I. To estimate minimal/measurable residual disease (MRD) negativity (among patients who
      achieve CR or CRi).

      II. To bank specimens for future research.

      OUTLINE:

      Patients receive AKR1C3-activated prodrug OBI-3424 intravenously (IV) over 30 minutes on days
      1 and 8. Treatment repeats every 21 days for up to 17 cycles in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every month for 1 year, every 2
      months for 1 year, every 3 months for 1 year, and then every 6 months for up to 5 years from
      registration.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (AKR1C3-activated prodrug OBI-3424)ExperimentalPatients receive AKR1C3-activated prodrug OBI-3424 IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity.
  • AKR1C3-activated Prodrug OBI-3424

Eligibility 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. Note that
             patients who were diagnosed initially with lymphoblastic lymphoma but who have
             relapsed with T-ALL are eligible

          -  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 must be refractory to or have relapsed following prior standard induction
             therapy. A standard induction regimen is defined as any program of treatment that
             includes:

               -  Vincristine and prednisone

               -  Vincristine and dexamethasone

               -  Cytarabine and anthracycline, or

               -  High dose cytarabine

          -  Patients must have no evidence of central nervous system disease within 28 days prior
             to registration. 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. Note that the patients may receive intrathecal chemotherapy with the
             initial lumbar puncture

          -  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

          -  Patients must be >= 18 years of age

          -  Patients must have a Zubrod performance status of 0-3

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

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

          -  Patients must have aspartate aminotransferase (AST) and 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) (within 14 days prior to registration to obtain baseline measurements)

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

          -  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 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 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 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 institutional and federal
             guidelines

          -  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

        Exclusion Criteria:

          -  Patients must not have had chemotherapy within 14 days prior to registration except
             for steroids, oral 6-mercaptopurine, oral methotrexate, vincristine, intrathecal
             chemotherapy, or hydroxyurea

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

          -  Patients must have 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. 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 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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate (complete remission [CR] or CR with incomplete count recovery [CRi])
Time Frame:Up to 5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to the time of relapse, assessed up to 5 years
Safety Issue:
Description:Toxicities will be captured and described. The probability of any particular toxicity can be estimated to within at most +/- 17% (95% confidence interval).
Measure:Overall survival
Time Frame:From the day of registration on study until death from any cause with observations censored on the day of last contact for patients not known to have died, assessed up to 5 years
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method.
Measure:Event-free survival
Time Frame:From the date of initial registration on study until the first of the following events: death from any cause, relapse from remission (CR or CRi) or completion of protocol therapy without documentation of CR or CRi, assessed up to 5 years
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method.
Measure:Relapse-free survival
Time Frame:From the date the patient first achieves CR or CRi until relapse from CR/CRi or death from any cause, assessed up to 5 years
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Southwest Oncology Group

Last Updated

September 15, 2020