Study to Test AKR1C3-Activated Prodrug OBI-3424 (OBI-3424) in Patients With Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL)
- Conditions
- Refractory T Acute Lymphoblastic LeukemiaRecurrent T Acute Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT04315324
- Lead Sponsor
- SWOG Cancer Research Network
- 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.
- 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 assess AKR1C3 expression levels in this patient population. III. c. To evaluate associations between AKR1C3 expression and response to OBI-3423, achievement of MRD-negative remission, and relapse from remission.
IV. 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 39
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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
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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
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Patients must be refractory to or have relapsed following a standard induction chemotherapy. A standard chemotherapy induction regimen is defined as any program of treatment that includes:
- Vincristine and prednisone
- Vincristine and dexamethasone
- Cytarabine and anthracycline, or
- High dose cytarabine (defined as at least 1 gr/m2 per individual dose unless adjustments were required for renal/liver function)
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Patients must have no evidence of central nervous system disease within 28 days prior to registration based on 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. Note that the patients may receive intrathecal chemotherapy with the initial lumbar puncture
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Prior nelarabine therapy is not required. In addition, patients who 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
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Patients must be >= 18 years of age
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Patients must have a Zubrod performance status of 0-3
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Patients must have creatinine clearance > 30 mL/min within 14 days prior to registration according to the Cockcroft Gault equation
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Patients must have direct bilirubin =< 1.5 x institutional upper limit of normal (ULN) within 14 days prior to registration
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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
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Prothrombin time (PT)/partial thromboplastin time (PTT)/fibrinogen (as clinically indicated) (within 14 days prior to registration to obtain baseline measurements)
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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)
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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)
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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)
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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)
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Patients must agree to have bone marrow and blood specimens submitted for MRD testing
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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
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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
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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
- Patients must not have had chemotherapy or investigational agents within 14 days prior to registration except for steroids, 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 >= 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (AKR1C3-activated prodrug OBI-3424) 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.
- Primary Outcome Measures
Name Time Method Response rate (complete remission [CR] or CR with incomplete count recovery [CRi]) Up to 5 years
- Secondary Outcome Measures
Name Time Method 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.
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).
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.
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.
Trial Locations
- Locations (116)
McFarland Clinic - Trinity Cancer Center
🇺🇸Fort Dodge, Iowa, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Cancer and Blood Specialists-Henderson
🇺🇸Henderson, Nevada, United States
Las Vegas Cancer Center-Henderson
🇺🇸Henderson, Nevada, United States
Las Vegas Urology - Green Valley
🇺🇸Henderson, Nevada, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
Las Vegas Urology - Pebble
🇺🇸Henderson, Nevada, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸New Richmond, Wisconsin, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Hope Cancer Care of Nevada
🇺🇸Las Vegas, Nevada, United States
Radiation Oncology Centers of Nevada Central
🇺🇸Las Vegas, Nevada, United States
GenesisCare USA - Las Vegas
🇺🇸Las Vegas, Nevada, United States
HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
🇺🇸Las Vegas, Nevada, United States
Sunrise Hospital and Medical Center
🇺🇸Las Vegas, Nevada, United States
HealthCare Partners Medical Group Oncology/Hematology-San Martin
🇺🇸Las Vegas, Nevada, United States
Las Vegas Prostate Cancer Center
🇺🇸Las Vegas, Nevada, United States
Las Vegas Urology - Sunset
🇺🇸Las Vegas, Nevada, United States
Urology Specialists of Nevada - Southwest
🇺🇸Las Vegas, Nevada, United States
Radiation Oncology Centers of Nevada Southeast
🇺🇸Las Vegas, Nevada, United States
Ann M Wierman MD LTD
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Northwest
🇺🇸Las Vegas, Nevada, United States
GenesisCare USA - Vegas Tenaya
🇺🇸Las Vegas, Nevada, United States
Las Vegas Urology - Cathedral Rock
🇺🇸Las Vegas, Nevada, United States
Las Vegas Urology - Smoke Ranch
🇺🇸Las Vegas, Nevada, United States
OptumCare Cancer Care at MountainView
🇺🇸Las Vegas, Nevada, United States
Urology Specialists of Nevada - Northwest
🇺🇸Las Vegas, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada-Summerlin
🇺🇸Las Vegas, Nevada, United States
OptumCare Cancer Care at Fort Apache
🇺🇸Las Vegas, Nevada, United States
FHCC South Lake Union
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Health Partners Inc
🇺🇸Minneapolis, Minnesota, United States
Saint Francis Regional Medical Center
🇺🇸Shakopee, Minnesota, United States
Kingman Regional Medical Center
🇺🇸Kingman, Arizona, United States
Weisberg Cancer Treatment Center
🇺🇸Farmington Hills, Michigan, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Carson Tahoe Regional Medical Center
🇺🇸Carson City, Nevada, United States
Comprehensive Cancer Centers of Nevada - Henderson
🇺🇸Henderson, Nevada, United States
OptumCare Cancer Care at Seven Hills
🇺🇸Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada-Horizon Ridge
🇺🇸Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada-Southeast Henderson
🇺🇸Henderson, Nevada, United States
GenesisCare USA - Henderson
🇺🇸Henderson, Nevada, United States
Las Vegas Urology - Pecos
🇺🇸Las Vegas, Nevada, United States
Desert West Surgery
🇺🇸Las Vegas, Nevada, United States
Urology Specialists of Nevada - Green Valley
🇺🇸Henderson, Nevada, United States
OptumCare Cancer Care at Charleston
🇺🇸Las Vegas, Nevada, United States
Urology Specialists of Nevada - Central
🇺🇸Las Vegas, Nevada, United States
HealthCare Partners Medical Group Oncology/Hematology-Tenaya
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Town Center
🇺🇸Las Vegas, Nevada, United States
Las Vegas Cancer Center-Medical Center
🇺🇸Las Vegas, Nevada, United States
Summerlin Hospital Medical Center
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
GenesisCare USA - Fort Apache
🇺🇸Las Vegas, Nevada, United States
HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Central Valley
🇺🇸Las Vegas, Nevada, United States
University Cancer Center
🇺🇸Las Vegas, Nevada, United States
Hope Cancer Care of Nevada-Pahrump
🇺🇸Pahrump, Nevada, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Saint Mary's Regional Medical Center
🇺🇸Reno, Nevada, United States
Radiation Oncology Associates
🇺🇸Reno, Nevada, United States
Minnesota Oncology - Burnsville
🇺🇸Burnsville, Minnesota, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
Fairview Northland Medical Center
🇺🇸Princeton, Minnesota, United States
Cambridge Medical Center
🇺🇸Cambridge, Minnesota, United States
Fairview Clinics and Surgery Center Maple Grove
🇺🇸Maple Grove, Minnesota, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Monticello Cancer Center
🇺🇸Monticello, Minnesota, United States
Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Fairview Lakes Medical Center
🇺🇸Wyoming, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
New Ulm Medical Center
🇺🇸New Ulm, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Loyola Center for Health at Burr Ridge
🇺🇸Burr Ridge, Illinois, United States
PCR Oncology
🇺🇸Arroyo Grande, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Marjorie Weinberg Cancer Center at Loyola-Gottlieb
🇺🇸Melrose Park, Illinois, United States
Loyola Medicine Homer Glen
🇺🇸Homer Glen, Illinois, United States
Northwestern Medicine Lake Forest Hospital
🇺🇸Lake Forest, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
🇺🇸New Lenox, Illinois, United States
Mary Greeley Medical Center
🇺🇸Ames, Iowa, United States
McFarland Clinic - Ames
🇺🇸Ames, Iowa, United States
McFarland Clinic - Jefferson
🇺🇸Jefferson, Iowa, United States
McFarland Clinic - Marshalltown
🇺🇸Marshalltown, Iowa, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
University of Cincinnati Cancer Center-UC Medical Center
🇺🇸Cincinnati, Ohio, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Overlake Medical Center
🇺🇸Bellevue, Washington, United States
University of Cincinnati Cancer Center-West Chester
🇺🇸West Chester, Ohio, United States
Valley Medical Center
🇺🇸Renton, Washington, United States
University of Washington Medical Center - Montlake
🇺🇸Seattle, Washington, United States
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
🇺🇸Yakima, Washington, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
University of Chicago Medicine-Orland Park
🇺🇸Orland Park, Illinois, United States
McFarland Clinic - Boone
🇺🇸Boone, Iowa, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States