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

Sponsor
Southwest Oncology Group (Other)
Overall Status
Recruiting
CT.gov ID
NCT04315324
Collaborator
National Cancer Institute (NCI) (NIH)
39
Enrollment
108
Locations
1
Arm
83.4
Anticipated Duration (Months)
0.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: AKR1C3-activated Prodrug OBI-3424
 Phase 2

Detailed Description

PRIMARY OBJECTIVE:
  1. 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:

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

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

TRANSLATIONAL MEDICINE OBJECTIVES:

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

  2. 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
39 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Aug 17, 2020
Anticipated Primary Completion Date :
Aug 1, 2026
Anticipated Study Completion Date :
Aug 1, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (AKR1C3-activated prodrug OBI-3424)

Patients 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.

Drug: AKR1C3-activated Prodrug OBI-3424
Given IV
Other Names:
  • AKR1C3-activated Prodrug TH-3424
  • Aldo-keto Reductase 1c3-activated Prodrug OBI-3424
  • OBI 3424
  • OBI-3424
  • OBI3424
  • TH 3424
  • TH-3424
  • TH3424

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Response rate (complete remission [CR] or CR with incomplete count recovery [CRi]) [Up to 5 years]

    Secondary Outcome Measures

    1. Incidence of adverse events [Up to the time of relapse, assessed up to 5 years]

      Toxicities will be captured and described. The probability of any particular toxicity can be estimated to within at most +/- 17% (95% confidence interval).

    2. Overall survival [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]

      Will be estimated using the Kaplan-Meier method.

    3. Event-free survival [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]

      Will be estimated using the Kaplan-Meier method.

    4. Relapse-free survival [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]

      Will be estimated using the Kaplan-Meier method.

    Other Outcome Measures

    1. Minimal residual disease (MRD) rate [Up to 5 years]

      The MRD rate for responders will be reported as a point estimate with an exact binomial confidence interval.

    2. AKR1C3 expression [Up to 5 years]

      A post-hoc analysis of AKR1C3 expression is planned.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Kingman Regional Medical Center Kingman Arizona United States 86401
    2 PCR Oncology Arroyo Grande California United States 93420
    3 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    4 Emory University Hospital/Winship Cancer Institute Atlanta Georgia United States 30322
    5 Loyola Center for Health at Burr Ridge Burr Ridge Illinois United States 60527
    6 Northwestern University Chicago Illinois United States 60611
    7 University of Illinois Chicago Illinois United States 60612
    8 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    9 Loyola Medicine Homer Glen Homer Glen Illinois United States 60491
    10 Northwestern Medicine Lake Forest Hospital Lake Forest Illinois United States 60045
    11 Loyola University Medical Center Maywood Illinois United States 60153
    12 Marjorie Weinberg Cancer Center at Loyola-Gottlieb Melrose Park Illinois United States 60160
    13 UC Comprehensive Cancer Center at Silver Cross New Lenox Illinois United States 60451
    14 University of Chicago Medicine-Orland Park Orland Park Illinois United States 60462
    15 Mary Greeley Medical Center Ames Iowa United States 50010
    16 McFarland Clinic PC - Ames Ames Iowa United States 50010
    17 McFarland Clinic PC-Boone Boone Iowa United States 50036
    18 McFarland Clinic PC-Trinity Cancer Center Fort Dodge Iowa United States 50501
    19 McFarland Clinic PC-Jefferson Jefferson Iowa United States 50129
    20 McFarland Clinic PC-Marshalltown Marshalltown Iowa United States 50158
    21 Fairview Ridges Hospital Burnsville Minnesota United States 55337
    22 Minnesota Oncology - Burnsville Burnsville Minnesota United States 55337
    23 Cambridge Medical Center Cambridge Minnesota United States 55008
    24 Mercy Hospital Coon Rapids Minnesota United States 55433
    25 Fairview Southdale Hospital Edina Minnesota United States 55435
    26 Unity Hospital Fridley Minnesota United States 55432
    27 Fairview Clinics and Surgery Center Maple Grove Maple Grove Minnesota United States 55369
    28 Minnesota Oncology Hematology PA-Maplewood Maplewood Minnesota United States 55109
    29 Saint John's Hospital - Healtheast Maplewood Minnesota United States 55109
    30 Abbott-Northwestern Hospital Minneapolis Minnesota United States 55407
    31 Hennepin County Medical Center Minneapolis Minnesota United States 55415
    32 Health Partners Inc Minneapolis Minnesota United States 55454
    33 Monticello Cancer Center Monticello Minnesota United States 55362
    34 New Ulm Medical Center New Ulm Minnesota United States 56073
    35 Fairview Northland Medical Center Princeton Minnesota United States 55371
    36 North Memorial Medical Health Center Robbinsdale Minnesota United States 55422
    37 Park Nicollet Clinic - Saint Louis Park Saint Louis Park Minnesota United States 55416
    38 Regions Hospital Saint Paul Minnesota United States 55101
    39 United Hospital Saint Paul Minnesota United States 55102
    40 Saint Francis Regional Medical Center Shakopee Minnesota United States 55379
    41 Lakeview Hospital Stillwater Minnesota United States 55082
    42 Ridgeview Medical Center Waconia Minnesota United States 55387
    43 Rice Memorial Hospital Willmar Minnesota United States 56201
    44 Minnesota Oncology Hematology PA-Woodbury Woodbury Minnesota United States 55125
    45 Fairview Lakes Medical Center Wyoming Minnesota United States 55092
    46 Carson Tahoe Regional Medical Center Carson City Nevada United States 89703
    47 Cancer and Blood Specialists-Henderson Henderson Nevada United States 89052
    48 Comprehensive Cancer Centers of Nevada - Henderson Henderson Nevada United States 89052
    49 Comprehensive Cancer Centers of Nevada-Horizon Ridge Henderson Nevada United States 89052
    50 Las Vegas Cancer Center-Henderson Henderson Nevada United States 89052
    51 OptumCare Cancer Care at Seven Hills Henderson Nevada United States 89052
    52 21st Century Oncology-Henderson Henderson Nevada United States 89074
    53 Comprehensive Cancer Centers of Nevada-Southeast Henderson Henderson Nevada United States 89074
    54 Las Vegas Urology - Green Valley Henderson Nevada United States 89074
    55 Las Vegas Urology - Pebble Henderson Nevada United States 89074
    56 Urology Specialists of Nevada - Green Valley Henderson Nevada United States 89074
    57 Las Vegas Urology - Pecos Las Vegas Nevada United States 89074
    58 Desert West Surgery Las Vegas Nevada United States 89102
    59 OptumCare Cancer Care at Charleston Las Vegas Nevada United States 89102
    60 University Medical Center of Southern Nevada Las Vegas Nevada United States 89102
    61 Hope Cancer Care of Nevada Las Vegas Nevada United States 89103
    62 Radiation Oncology Centers of Nevada Central Las Vegas Nevada United States 89106
    63 Urology Specialists of Nevada - Central Las Vegas Nevada United States 89106
    64 21st Century Oncology Las Vegas Nevada United States 89109
    65 HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway Las Vegas Nevada United States 89109
    66 Sunrise Hospital and Medical Center Las Vegas Nevada United States 89109
    67 HealthCare Partners Medical Group Oncology/Hematology-San Martin Las Vegas Nevada United States 89113
    68 Las Vegas Prostate Cancer Center Las Vegas Nevada United States 89113
    69 Las Vegas Urology - Sunset Las Vegas Nevada United States 89113
    70 Urology Specialists of Nevada - Southwest Las Vegas Nevada United States 89113
    71 Radiation Oncology Centers of Nevada Southeast Las Vegas Nevada United States 89119
    72 21st Century Oncology-Vegas Tenaya Las Vegas Nevada United States 89128
    73 Ann M Wierman MD LTD Las Vegas Nevada United States 89128
    74 Comprehensive Cancer Centers of Nevada - Northwest Las Vegas Nevada United States 89128
    75 HealthCare Partners Medical Group Oncology/Hematology-Tenaya Las Vegas Nevada United States 89128
    76 Las Vegas Urology - Cathedral Rock Las Vegas Nevada United States 89128
    77 Las Vegas Urology - Smoke Ranch Las Vegas Nevada United States 89128
    78 OptumCare Cancer Care at MountainView Las Vegas Nevada United States 89128
    79 Urology Specialists of Nevada - Northwest Las Vegas Nevada United States 89128
    80 Alliance for Childhood Diseases/Cure 4 the Kids Foundation Las Vegas Nevada United States 89135
    81 Comprehensive Cancer Centers of Nevada - Town Center Las Vegas Nevada United States 89144
    82 Comprehensive Cancer Centers of Nevada-Summerlin Las Vegas Nevada United States 89144
    83 Summerlin Hospital Medical Center Las Vegas Nevada United States 89144
    84 Las Vegas Cancer Center-Medical Center Las Vegas Nevada United States 89148-2405
    85 21st Century Oncology-Fort Apache Las Vegas Nevada United States 89148
    86 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89148
    87 OptumCare Cancer Care at Fort Apache Las Vegas Nevada United States 89148
    88 HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills Las Vegas Nevada United States 89149
    89 Comprehensive Cancer Centers of Nevada - Central Valley Las Vegas Nevada United States 89169
    90 University Cancer Center Las Vegas Nevada United States 89169
    91 Hope Cancer Care of Nevada-Pahrump Pahrump Nevada United States 89048
    92 Renown Regional Medical Center Reno Nevada United States 89502
    93 Saint Mary's Regional Medical Center Reno Nevada United States 89503
    94 Radiation Oncology Associates Reno Nevada United States 89509
    95 University of Rochester Rochester New York United States 14642
    96 University of Cincinnati Cancer Center-UC Medical Center Cincinnati Ohio United States 45219
    97 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    98 Oregon Health and Science University Portland Oregon United States 97239
    99 Huntsman Cancer Institute/University of Utah Salt Lake City Utah United States 84112
    100 Virginia Commonwealth University/Massey Cancer Center Richmond Virginia United States 23298
    101 Overlake Medical Center Bellevue Washington United States 98004
    102 Valley Medical Center Renton Washington United States 98055
    103 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109
    104 Seattle Cancer Care Alliance Seattle Washington United States 98109
    105 University of Washington Medical Center - Montlake Seattle Washington United States 98195
    106 North Star Lodge Cancer Center at Yakima Valley Memorial Hospital Yakima Washington United States 98902
    107 West Virginia University Healthcare Morgantown West Virginia United States 26506
    108 Cancer Center of Western Wisconsin New Richmond Wisconsin United States 54017

    Sponsors and Collaborators

    • Southwest Oncology Group
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Anjali S Advani, Southwest Oncology Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Southwest Oncology Group
    ClinicalTrials.gov Identifier:
    NCT04315324
    Other Study ID Numbers:
    • S1905
    • NCI-2020-00768
    • S1905
    • S1905
    • U10CA180888
    First Posted:
    Mar 19, 2020
    Last Update Posted:
    Nov 9, 2021
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Leukemia
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Leukemia, Lymphoid
    Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

    Study Results

    No Results Posted as of Nov 9, 2021