Clinical trial NCT04315324: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Recurrent T Acute Lymphoblastic Leukemia
Refractory T Acute Lymphoblastic Leukemia
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-03-19
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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)
* 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
* 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
* 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 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.

Primary outcomes:
measure: Response rate (complete remission [CR] or CR with incomplete count recovery [CRi])
timeFrame: Up to 5 years
Secondary outcomes:
measure: Incidence of adverse events
timeFrame: Up to the time of relapse, assessed up to 5 years
measure: Overall survival
timeFrame: 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
measure: Event-free survival
timeFrame: 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
measure: Relapse-free survival
timeFrame: 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
Other outcomes:
measure: Minimal residual disease (MRD) rate
timeFrame: Up to 5 years
measure: AKR1C3 expression
timeFrame: Up to 5 years
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Kingman
country: United States
facility: Kingman Regional Medical Center
state: Arizona
city: Arroyo Grande
country: United States
facility: PCR Oncology
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Burr Ridge
country: United States
facility: Loyola Center for Health at Burr Ridge
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Homer Glen
country: United States
facility: Loyola Medicine Homer Glen
state: Illinois
city: Lake Forest
country: United States
facility: Northwestern Medicine Lake Forest Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Melrose Park
country: United States
facility: Marjorie Weinberg Cancer Center at Loyola-Gottlieb
state: Illinois
city: New Lenox
country: United States
facility: UC Comprehensive Cancer Center at Silver Cross
state: Illinois
city: Orland Park
country: United States
facility: University of Chicago Medicine-Orland Park
state: Illinois
city: Ames
country: United States
facility: Mary Greeley Medical Center
state: Iowa
city: Ames
country: United States
facility: McFarland Clinic - Ames
state: Iowa
city: Boone
country: United States
facility: McFarland Clinic - Boone
state: Iowa
city: Fort Dodge
country: United States
facility: McFarland Clinic - Trinity Cancer Center
state: Iowa
city: Jefferson
country: United States
facility: McFarland Clinic - Jefferson
state: Iowa
city: Marshalltown
country: United States
facility: McFarland Clinic - Marshalltown
state: Iowa
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Farmington Hills
country: United States
facility: Weisberg Cancer Treatment Center
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Burnsville
country: United States
facility: Minnesota Oncology - Burnsville
state: Minnesota
city: Cambridge
country: United States
facility: Cambridge Medical Center
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Unity Hospital
state: Minnesota
city: Maple Grove
country: United States
facility: Fairview Clinics and Surgery Center Maple Grove
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology PA-Maplewood
state: Minnesota
city: Maplewood
country: United States
facility: Saint John's Hospital - Healtheast
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: Health Partners Inc
state: Minnesota
city: Monticello
country: United States
facility: Monticello Cancer Center
state: Minnesota
city: New Ulm
country: United States
facility: New Ulm Medical Center
state: Minnesota
city: Princeton
country: United States
facility: Fairview Northland Medical Center
state: Minnesota
city: Robbinsdale
country: United States
facility: North Memorial Medical Health Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Clinic - Saint Louis Park
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: Saint Francis Regional Medical Center
state: Minnesota
city: Stillwater
country: United States
facility: Lakeview Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Willmar
country: United States
facility: Rice Memorial Hospital
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology PA-Woodbury
state: Minnesota
city: Wyoming
country: United States
facility: Fairview Lakes Medical Center
state: Minnesota
city: Carson City
country: United States
facility: Carson Tahoe Regional Medical Center
state: Nevada
city: Henderson
country: United States
facility: Cancer and Blood Specialists-Henderson
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada - Henderson
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada-Horizon Ridge
state: Nevada
city: Henderson
country: United States
facility: Las Vegas Cancer Center-Henderson
state: Nevada
city: Henderson
country: United States
facility: OptumCare Cancer Care at Seven Hills
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada-Southeast Henderson
state: Nevada
city: Henderson
country: United States
facility: GenesisCare USA - Henderson
state: Nevada
city: Henderson
country: United States
facility: Las Vegas Urology - Green Valley
state: Nevada
city: Henderson
country: United States
facility: Las Vegas Urology - Pebble
state: Nevada
city: Henderson
country: United States
facility: Urology Specialists of Nevada - Green Valley
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Urology - Pecos
state: Nevada
city: Las Vegas
country: United States
facility: Desert West Surgery
state: Nevada
city: Las Vegas
country: United States
facility: OptumCare Cancer Care at Charleston
state: Nevada
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Hope Cancer Care of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Radiation Oncology Centers of Nevada Central
state: Nevada
city: Las Vegas
country: United States
facility: Urology Specialists of Nevada - Central
state: Nevada
city: Las Vegas
country: United States
facility: GenesisCare USA - Las Vegas
state: Nevada
city: Las Vegas
country: United States
facility: HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
state: Nevada
city: Las Vegas
country: United States
facility: Sunrise Hospital and Medical Center
state: Nevada
city: Las Vegas
country: United States
facility: HealthCare Partners Medical Group Oncology/Hematology-San Martin
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Prostate Cancer Center
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Urology - Sunset
state: Nevada
city: Las Vegas
country: United States
facility: Urology Specialists of Nevada - Southwest
state: Nevada
city: Las Vegas
country: United States
facility: Radiation Oncology Centers of Nevada Southeast
state: Nevada
city: Las Vegas
country: United States
facility: Ann M Wierman MD LTD
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Northwest
state: Nevada
city: Las Vegas
country: United States
facility: GenesisCare USA - Vegas Tenaya
state: Nevada
city: Las Vegas
country: United States
facility: HealthCare Partners Medical Group Oncology/Hematology-Tenaya
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Urology - Cathedral Rock
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Urology - Smoke Ranch
state: Nevada
city: Las Vegas
country: United States
facility: OptumCare Cancer Care at MountainView
state: Nevada
city: Las Vegas
country: United States
facility: Urology Specialists of Nevada - Northwest
state: Nevada
city: Las Vegas
country: United States
facility: Alliance for Childhood Diseases/Cure 4 the Kids Foundation
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Town Center
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada-Summerlin
state: Nevada
city: Las Vegas
country: United States
facility: Summerlin Hospital Medical Center
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Cancer Center-Medical Center
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: GenesisCare USA - Fort Apache
state: Nevada
city: Las Vegas
country: United States
facility: OptumCare Cancer Care at Fort Apache
state: Nevada
city: Las Vegas
country: United States
facility: HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Central Valley
state: Nevada
city: Las Vegas
country: United States
facility: University Cancer Center
state: Nevada
city: Pahrump
country: United States
facility: Hope Cancer Care of Nevada-Pahrump
state: Nevada
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Reno
country: United States
facility: Saint Mary's Regional Medical Center
state: Nevada
city: Reno
country: United States
facility: Radiation Oncology Associates
state: Nevada
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Center-UC Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: West Chester
country: United States
facility: University of Cincinnati Cancer Center-West Chester
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Bellevue
country: United States
facility: Overlake Medical Center
state: Washington
city: Renton
country: United States
facility: Valley Medical Center
state: Washington
city: Seattle
country: United States
facility: FHCC South Lake Union
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center - Montlake
state: Washington
city: Yakima
country: United States
facility: North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Healthcare
state: West Virginia
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
city: New Richmond
country: United States
facility: Cancer Center of Western Wisconsin
state: Wisconsin
Study officials:
affiliation: SWOG Cancer Research Network
name: Anjali S Advani
role: PRINCIPAL_INVESTIGATOR
References: