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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) or T-Cell Lymphoblastic Lymphoma (T-LBL)

Trial Status: Active

This phase I / II trial studies the side effects and best dose of OBI-3424 and how well it works in treating patients with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Chemotherapy drugs, 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.

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 T-cell lymphoblastic lymphoma are eligible if lymphoblasts are >= 5% in the bone marrow or in the peripheral blood
  • 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 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: * Vincristine and corticosteroids plus at least one more chemotherapy agent * 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 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 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 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. For participants with impaired decision making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (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

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. 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
  • 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 have a known history of prolonged QT interval by Fridericia (QTcF) (interval > 450 msec for males; > 470 msec for females)
  • 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

Arizona

Kingman
Kingman Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013

California

Arroyo Grande
PCR Oncology
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Duarte
City of Hope Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-826-4673

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 404-778-1868

Illinois

Burr Ridge
Loyola Center for Health at Burr Ridge
Status: ACTIVE
Contact: Site Public Contact
Phone: 708-216-9000
Chicago
Northwestern University
Status: ACTIVE
Contact: Site Public Contact
Phone: 312-695-1301
University of Chicago Comprehensive Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 773-702-8222
University of Illinois
Status: ACTIVE
Contact: Site Public Contact
Phone: 312-355-3046
Homer Glen
Loyola Medicine Homer Glen
Status: ACTIVE
Contact: Site Public Contact
Phone: 708-216-9000
Lake Forest
Northwestern Medicine Lake Forest Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Maywood
Loyola University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 708-226-4357
Melrose Park
Marjorie Weinberg Cancer Center at Loyola-Gottlieb
Status: ACTIVE
Contact: Site Public Contact
Phone: 708-450-4554
New Lenox
UC Comprehensive Cancer Center at Silver Cross
Status: ACTIVE
Contact: Site Public Contact
Phone: 773-702-8222
Orland Park
University of Chicago Medicine-Orland Park
Status: ACTIVE
Contact: Site Public Contact
Phone: 773-702-8222

Iowa

Ames
Mary Greeley Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-956-4132
McFarland Clinic PC - Ames
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-239-4734
Boone
McFarland Clinic PC-Boone
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-956-4132
Fort Dodge
McFarland Clinic PC-Trinity Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-956-4132
Jefferson
McFarland Clinic PC-Jefferson
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-956-4132
Marshalltown
McFarland Clinic PC-Marshalltown
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-956-4132

Minnesota

Burnsville
Fairview Ridges Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Minnesota Oncology - Burnsville
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Cambridge
Cambridge Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Coon Rapids
Mercy Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Edina
Fairview Southdale Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Fridley
Unity Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Maple Grove
Fairview Clinics and Surgery Center Maple Grove
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Maplewood
Minnesota Oncology Hematology PA-Maplewood
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Saint John's Hospital - Healtheast
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Minneapolis
Abbott-Northwestern Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Health Partners Inc
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Hennepin County Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Monticello
Monticello Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
New Ulm
New Ulm Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Princeton
Fairview Northland Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Robbinsdale
North Memorial Medical Health Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Saint Louis Park
Park Nicollet Clinic - Saint Louis Park
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Saint Paul
Regions Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
United Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Shakopee
Saint Francis Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Stillwater
Lakeview Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Waconia
Ridgeview Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Willmar
Rice Memorial Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Woodbury
Minnesota Oncology Hematology PA-Woodbury
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517
Wyoming
Fairview Lakes Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517

Nevada

Carson City
Carson Tahoe Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Henderson
21st Century Oncology-Henderson
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Cancer and Blood Specialists-Henderson
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada - Henderson
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada-Horizon Ridge
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada-Southeast Henderson
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Las Vegas Cancer Center-Henderson
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Las Vegas Urology - Green Valley
Status: ACTIVE
Contact: Site Public Contact
Las Vegas Urology - Pebble
Status: ACTIVE
Contact: Site Public Contact
OptumCare Cancer Care at Seven Hills
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Urology Specialists of Nevada - Green Valley
Status: ACTIVE
Contact: Site Public Contact
Las Vegas
21st Century Oncology
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
21st Century Oncology-Fort Apache
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
21st Century Oncology-Vegas Tenaya
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Alliance for Childhood Diseases / Cure 4 the Kids Foundation
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Ann M Wierman MD LTD
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada - Central Valley
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada - Northwest
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada - Town Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada-Summerlin
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Desert West Surgery
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
HealthCare Partners Medical Group Oncology / Hematology-Centennial Hills
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
HealthCare Partners Medical Group Oncology / Hematology-Maryland Parkway
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
HealthCare Partners Medical Group Oncology / Hematology-San Martin
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
HealthCare Partners Medical Group Oncology / Hematology-Tenaya
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Hope Cancer Care of Nevada
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Las Vegas Cancer Center-Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Las Vegas Prostate Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Las Vegas Urology - Cathedral Rock
Status: ACTIVE
Contact: Site Public Contact
Las Vegas Urology - Pecos
Status: ACTIVE
Contact: Site Public Contact
Las Vegas Urology - Smoke Ranch
Status: ACTIVE
Contact: Site Public Contact
Las Vegas Urology - Sunset
Status: ACTIVE
Contact: Site Public Contact
OptumCare Cancer Care at Charleston
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
OptumCare Cancer Care at Fort Apache
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
OptumCare Cancer Care at MountainView
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Radiation Oncology Centers of Nevada Central
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Radiation Oncology Centers of Nevada Southeast
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Summerlin Hospital Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Sunrise Hospital and Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
University Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
University Medical Center of Southern Nevada
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Urology Specialists of Nevada - Central
Status: ACTIVE
Contact: Site Public Contact
Urology Specialists of Nevada - Northwest
Status: ACTIVE
Contact: Site Public Contact
Urology Specialists of Nevada - Southwest
Status: ACTIVE
Contact: Site Public Contact
Pahrump
Hope Cancer Care of Nevada-Pahrump
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Reno
Radiation Oncology Associates
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Renown Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Saint Mary's Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013

New York

Rochester
University of Rochester
Status: ACTIVE
Contact: Site Public Contact
Phone: 585-275-5830

Ohio

Cincinnati
University of Cincinnati Cancer Center-UC Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 513-584-7698
Cleveland
Cleveland Clinic Foundation
Status: ACTIVE
Contact: Site Public Contact
Phone: 866-223-8100

Oregon

Portland
Oregon Health and Science University
Status: ACTIVE
Contact: Site Public Contact
Phone: 503-494-1080

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: ACTIVE
Contact: Site Public Contact
Phone: 888-424-2100

Virginia

Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: ACTIVE
Contact: Site Public Contact

Washington

Bellevue
Overlake Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 425-688-5407
Renton
Valley Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 425-228-3440
Seattle
Fred Hutchinson Cancer Research Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-804-8824
Seattle Cancer Care Alliance
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-804-8824
University of Washington Medical Center - Montlake
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-804-8824
Yakima
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 509-574-3535

West Virginia

Morgantown
West Virginia University Healthcare
Status: ACTIVE
Contact: Site Public Contact
Phone: 304-293-7374

Wisconsin

New Richmond
Cancer Center of Western Wisconsin
Status: ACTIVE
Contact: Site Public Contact
Phone: 952-993-1517

PRIMARY OBJECTIVES:

I. To assess the safety of AKR1C3-activated prodrug OBI-3424 (OBI‐3424) and to determine the maximum tolerated dose (MTD) of OBI‐3424 in this regimen for patients with relapsed/refractory T‐cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LBL). (Phase I)

II. To assess the response rate (complete remission [CR] or CR with incomplete count recovery [CRi]) of patients treated with OBI‐3424 at the MTD determined in the Phase I portion of the trial in this patient population. (Phase II)

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: This is a phase I, dose-escalation study followed by a phase II study.

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. Patients who have not achieved a partial remission (PR) by the 4th cycle of treatment are removed from the study (unless clinically benefitting in the opinion of the treating investigator).

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 Phase Phase I/II

Trial Type Treatment

Lead Organization
SWOG

Principal Investigator
Anjali S. Advani

  • Primary ID S1905
  • Secondary IDs NCI-2020-00768
  • Clinicaltrials.gov ID NCT04315324