Back to Trials
NCT04315324PHASE1, PHASE2Recruiting

Study to Test OBI-3424 in Patients With T-Cell Acute Lymphoblastic Leukemia (T-ALL) or T-Cell Lymphoblastic Lymphoma (T-LBL)

SWOG Cancer Research Network

Start Date

2/8/2021

Completion Date

8/1/2028

Summary

This phase I/II trial studies the safety, 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.

Detailed Description

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 maximum tolerated dose (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 assess AKR1C3 expression levels in this patient population. III. To evaluate associations between AKR1C3 expression and response to OBI-3424, achievement of MRD-negative remission, and relapse from remission. IV. 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 benefiting in the opinion of the treating investigator). Patients undergo blood sample collection during screening and cerebrospinal fluid (CSF) sample collection on study. Patients also undergo bone marrow aspirate or core biopsy and may undergo computed tomography (CT) scan throughout the study. 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.

Eligibility Criteria

Age Range: 12 years to No maximum

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

Interventions

DRUG

AKR1C3-activated Prodrug AST-3424

PROCEDURE

Biopsy Procedure

PROCEDURE

Biospecimen Collection

PROCEDURE

Bone Marrow Aspiration

PROCEDURE

Computed Tomography

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Recurrent T Acute Lymphoblastic LeukemiaRefractory T Acute Lymphoblastic LeukemiaRefractory T Lymphoblastic LymphomaT Lymphoblastic Lymphoma

Locations

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama 35233

United States

Kingman Regional Medical Center

Kingman, Arizona 86401

United States

Arkansas Children's Hospital

Little Rock, Arkansas 72202-3591

United States

PCR Oncology

Arroyo Grande, California 93420

United States

City of Hope Comprehensive Cancer Center

Duarte, California 91010

United States

Loma Linda University Medical Center

Loma Linda, California 92354

United States

Children's Hospital of Orange County

Orange, California 92868

United States

Children's Hospital Colorado

Aurora, Colorado 80045

United States

Alfred I duPont Hospital for Children

Wilmington, Delaware 19803

United States

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida 33908

United States

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida 33021

United States

Johns Hopkins All Children's Hospital

St. Petersburg, Florida 33701

United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia 30322

United States

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia 30329

United States

Augusta University Medical Center

Augusta, Georgia 30912

United States

Loyola Center for Health at Burr Ridge

Burr Ridge, Illinois 60527

United States

Lurie Children's Hospital-Chicago

Chicago, Illinois 60611

United States

Northwestern University

Chicago, Illinois 60611

United States

University of Illinois

Chicago, Illinois 60612

United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois 60637

United States

Loyola Medicine Homer Glen

Homer Glen, Illinois 60491

United States

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois 60045

United States

Loyola University Medical Center

Maywood, Illinois 60153

United States

Marjorie Weinberg Cancer Center at Loyola-Gottlieb

Melrose Park, Illinois 60160

United States

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois 60451

United States

University of Chicago Medicine-Orland Park

Orland Park, Illinois 60462

United States

Southern Illinois University School of Medicine

Springfield, Illinois 62702

United States

Mary Greeley Medical Center

Ames, Iowa 50010

United States

McFarland Clinic - Ames

Ames, Iowa 50010

United States

McFarland Clinic - Boone

Boone, Iowa 50036

United States

McFarland Clinic - Trinity Cancer Center

Fort Dodge, Iowa 50501

United States

McFarland Clinic - Jefferson

Jefferson, Iowa 50129

United States

McFarland Clinic - Marshalltown

Marshalltown, Iowa 50158

United States

Norton Children's Hospital

Louisville, Kentucky 40202

United States

LSU Health Baton Rouge-North Clinic

Baton Rouge, Louisiana 70805

United States

Our Lady of the Lake Physician Group

Baton Rouge, Louisiana 70808

United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland 21287

United States

Bronson Battle Creek

Battle Creek, Michigan 49017

United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan 48201

United States

Weisberg Cancer Treatment Center

Farmington Hills, Michigan 48334

United States

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan 49503

United States

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan 49503

United States

Trinity Health Grand Rapids Hospital

Grand Rapids, Michigan 49503

United States

Bronson Methodist Hospital

Kalamazoo, Michigan 49007

United States

West Michigan Cancer Center

Kalamazoo, Michigan 49007

United States

Beacon Kalamazoo Cancer Center

Kalamazoo, Michigan 49009

United States

Beacon Kalamazoo

Kalamazoo, Michigan 49048

United States

Trinity Health Muskegon Hospital

Muskegon, Michigan 49444

United States

Corewell Health Lakeland Hospitals - Niles Hospital

Niles, Michigan 49120

United States

Cancer and Hematology Centers of Western Michigan - Norton Shores

Norton Shores, Michigan 49444

United States

Corewell Health Reed City Hospital

Reed City, Michigan 49677

United States

Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

Saint Joseph, Michigan 49085

United States

Corewell Health Lakeland Hospitals - Saint Joseph Hospital

Saint Joseph, Michigan 49085

United States

Munson Medical Center

Traverse City, Michigan 49684

United States

University of Michigan Health - West

Wyoming, Michigan 49519

United States

Fairview Ridges Hospital

Burnsville, Minnesota 55337

United States

Minnesota Oncology - Burnsville

Burnsville, Minnesota 55337

United States

Cambridge Medical Center

Cambridge, Minnesota 55008

United States

Mercy Hospital

Coon Rapids, Minnesota 55433

United States

Fairview Southdale Hospital

Edina, Minnesota 55435

United States

Unity Hospital

Fridley, Minnesota 55432

United States

Fairview Clinics and Surgery Center Maple Grove

Maple Grove, Minnesota 55369

United States

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota 55109

United States

Saint John's Hospital - Healtheast

Maplewood, Minnesota 55109

United States

Abbott-Northwestern Hospital

Minneapolis, Minnesota 55407

United States

Hennepin County Medical Center

Minneapolis, Minnesota 55415

United States

Health Partners Inc

Minneapolis, Minnesota 55454

United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota 55455

United States

Monticello Cancer Center

Monticello, Minnesota 55362

United States

New Ulm Medical Center

New Ulm, Minnesota 56073

United States

Fairview Northland Medical Center

Princeton, Minnesota 55371

United States

North Memorial Medical Health Center

Robbinsdale, Minnesota 55422

United States

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota 55416

United States

Regions Hospital

Saint Paul, Minnesota 55101

United States

United Hospital

Saint Paul, Minnesota 55102

United States

Saint Francis Regional Medical Center

Shakopee, Minnesota 55379

United States

Lakeview Hospital

Stillwater, Minnesota 55082

United States

Ridgeview Medical Center

Waconia, Minnesota 55387

United States

Rice Memorial Hospital

Willmar, Minnesota 56201

United States

Minnesota Oncology Hematology PA-Woodbury

Woodbury, Minnesota 55125

United States

Fairview Lakes Medical Center

Wyoming, Minnesota 55092

United States

Children's Mercy Hospitals and Clinics

Kansas City, Missouri 64108

United States

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska 68114

United States

University of Nebraska Medical Center

Omaha, Nebraska 68198

United States

Carson Tahoe Regional Medical Center

Carson City, Nevada 89703

United States

Cancer and Blood Specialists-Henderson

Henderson, Nevada 89052

United States

Comprehensive Cancer Centers of Nevada - Henderson

Henderson, Nevada 89052

United States

Comprehensive Cancer Centers of Nevada-Horizon Ridge

Henderson, Nevada 89052

United States

Las Vegas Cancer Center-Henderson

Henderson, Nevada 89052

United States

OptumCare Cancer Care at Seven Hills

Henderson, Nevada 89052

United States

Comprehensive Cancer Centers of Nevada-Southeast Henderson

Henderson, Nevada 89074

United States

GenesisCare USA - Henderson

Henderson, Nevada 89074

United States

Las Vegas Urology - Green Valley

Henderson, Nevada 89074

United States

Las Vegas Urology - Pebble

Henderson, Nevada 89074

United States

Urology Specialists of Nevada - Green Valley

Henderson, Nevada 89074

United States

Las Vegas Urology - Pecos

Las Vegas, Nevada 89074

United States

Desert West Surgery

Las Vegas, Nevada 89102

United States

OptumCare Cancer Care at Charleston

Las Vegas, Nevada 89102

United States

University Medical Center of Southern Nevada

Las Vegas, Nevada 89102

United States

Hope Cancer Care of Nevada

Las Vegas, Nevada 89103

United States

Radiation Oncology Centers of Nevada Central

Las Vegas, Nevada 89106

United States

Urology Specialists of Nevada - Central

Las Vegas, Nevada 89106

United States

GenesisCare USA - Las Vegas

Las Vegas, Nevada 89109

United States

HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway

Las Vegas, Nevada 89109

United States

Sunrise Hospital and Medical Center

Las Vegas, Nevada 89109

United States

HealthCare Partners Medical Group Oncology/Hematology-San Martin

Las Vegas, Nevada 89113

United States

Las Vegas Prostate Cancer Center

Las Vegas, Nevada 89113

United States

Las Vegas Urology - Sunset

Las Vegas, Nevada 89113

United States

Urology Specialists of Nevada - Southwest

Las Vegas, Nevada 89113

United States

Radiation Oncology Centers of Nevada Southeast

Las Vegas, Nevada 89119

United States

Ann M Wierman MD LTD

Las Vegas, Nevada 89128

United States

Comprehensive Cancer Centers of Nevada - Northwest

Las Vegas, Nevada 89128

United States

GenesisCare USA - Vegas Tenaya

Las Vegas, Nevada 89128

United States

HealthCare Partners Medical Group Oncology/Hematology-Tenaya

Las Vegas, Nevada 89128

United States

Las Vegas Urology - Cathedral Rock

Las Vegas, Nevada 89128

United States

Las Vegas Urology - Smoke Ranch

Las Vegas, Nevada 89128

United States

OptumCare Cancer Care at MountainView

Las Vegas, Nevada 89128

United States

Urology Specialists of Nevada - Northwest

Las Vegas, Nevada 89128

United States

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada 89135

United States

Comprehensive Cancer Centers of Nevada - Town Center

Las Vegas, Nevada 89144

United States

Comprehensive Cancer Centers of Nevada-Summerlin

Las Vegas, Nevada 89144

United States

Summerlin Hospital Medical Center

Las Vegas, Nevada 89144

United States

Las Vegas Cancer Center-Medical Center

Las Vegas, Nevada 89148-2405

United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada 89148

United States

GenesisCare USA - Fort Apache

Las Vegas, Nevada 89148

United States

OptumCare Cancer Care at Fort Apache

Las Vegas, Nevada 89148

United States

HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills

Las Vegas, Nevada 89149

United States

Comprehensive Cancer Centers of Nevada - Central Valley

Las Vegas, Nevada 89169

United States

University Cancer Center

Las Vegas, Nevada 89169

United States

Hope Cancer Care of Nevada-Pahrump

Pahrump, Nevada 89048

United States

Renown Regional Medical Center

Reno, Nevada 89502

United States

Saint Mary's Regional Medical Center

Reno, Nevada 89503

United States

Radiation Oncology Associates

Reno, Nevada 89509

United States

University of New Mexico Cancer Center

Albuquerque, New Mexico 87106

United States

Roswell Park Cancer Institute

Buffalo, New York 14263

United States

University of Rochester

Rochester, New York 14642

United States

Duke University Medical Center

Durham, North Carolina 27710

United States

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio 45219

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio 45229

United States

Cleveland Clinic Foundation

Cleveland, Ohio 44195

United States

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio 45069

United States

Oregon Health and Science University

Portland, Oregon 97239

United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania 19104

United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania 15224

United States

Rhode Island Hospital

Providence, Rhode Island 02903

United States

Prisma Health Richland Hospital

Columbia, South Carolina 29203

United States

The Children's Hospital at TriStar Centennial

Nashville, Tennessee 37203

United States

Dell Children's Medical Center of Central Texas

Austin, Texas 78723

United States

El Paso Children's Hospital

El Paso, Texas 79905

United States

Methodist Children's Hospital of South Texas

San Antonio, Texas 78229

United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas 78229

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah 84112

United States

University of Virginia Cancer Center

Charlottesville, Virginia 22908

United States

Children's Hospital of The King's Daughters

Norfolk, Virginia 23507

United States

VCU Massey Comprehensive Cancer Center

Richmond, Virginia 23298

United States

Overlake Medical Center

Bellevue, Washington 98004

United States

Valley Medical Center

Renton, Washington 98055

United States

Fred Hutchinson Cancer Center

Seattle, Washington 98109

United States

University of Washington Medical Center - Montlake

Seattle, Washington 98195

United States

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington 98902

United States

West Virginia University Healthcare

Morgantown, West Virginia 26506

United States

Gundersen Lutheran Medical Center

La Crosse, Wisconsin 54601

United States

Cancer Center of Western Wisconsin

New Richmond, Wisconsin 54017

United States