CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma
NCT ID: NCT04870944
Last Updated: 2025-12-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1/PHASE2
63 participants
INTERVENTIONAL
2022-01-28
2026-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of Facilitates Chromatin Transcription (FACT) complex-targeting curaxin CBL0137 (CBL0137) administered via infusion on Day 1 and Day 8 of a 21-day cycle to children with recurrent or refractory solid tumors, including CNS tumors and lymphoma. (Phase 1 Dose Escalation) II. To preliminarily determine the antitumor effects as measured by objective response rate of CBL0137 in children with progressive/recurrent diffuse intrinsic pontine glioma (DIPG) and other H3 K27-altered diffuse midline gliomas (DMG). (Phase 2)
SECONDARY OBJECTIVES:
I. To preliminarily determine the antitumor effects of CBL0137 in children with refractory solid tumors and other CNS tumors, to the extent possible in the context of a Phase 1 study.
II. To define and describe the toxicities of CBL0137 in children with recurrent or refractory solid tumors, including CNS tumors.
III. To characterize the pharmacokinetics of CBL0137 in children with recurrent or refractory solid tumors, including CNS tumors.
EXPLORATORY OBJECTIVES:
I. To measure biologic marker FACT in tumor specimens with potential for correlation with disease response.
II. To evaluate the effect of CBL0137 on immune response by measuring the effects on the interferon response pathway in peripheral blood mononuclear cells.
III. To preliminarily determine the effect of treatment with CBL0137 on overall survival of children with DIPG or other diffuse midline gliomas, H3 K27-altered, in comparison with historical controls.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive CBL0137 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 with pseudoprogression may remain on treatment, as per the treating physician. Patients also undergo echocardiography (ECHO) collection of blood samples throughout the trial. Patients may also undergo bone marrow aspirate and/or biopsy as clinically indicated.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48 and 60 months.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment (CBL0137)
Patients receive CBL0137 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 with pseudoprogression may remain on treatment, as per the treating physician. Patients also undergo ECHO collection of blood samples throughout the trial. Patients may also undergo bone marrow aspirate and/or biopsy as clinically indicated.
Biospecimen Collection
Undergo collection of blood samples
Bone Marrow Aspirate
Undergo bone marrow aspirate
Bone Marrow Biopsy
Undergo bone marrow biopsy
Echocardiography Test
Undergo ECHO
FACT Complex-targeting Curaxin CBL0137
Given IV
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Biospecimen Collection
Undergo collection of blood samples
Bone Marrow Aspirate
Undergo bone marrow aspirate
Bone Marrow Biopsy
Undergo bone marrow biopsy
Echocardiography Test
Undergo ECHO
FACT Complex-targeting Curaxin CBL0137
Given IV
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patients must have had histologic verification of malignancy at original diagnosis or relapse, except in patients with diffuse intrinsic brain stem tumors, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
* Part A: Patients with relapsed or refractory solid tumors or lymphoma, including patients with CNS tumors or known CNS metastases (including untreated or progressive) are eligible
* Part B: Patients with progressive or recurrent DIPG (diagnosed by biopsy or imaging characteristics) and other H3 K27-altered DMG previously treated with radiation therapy
* Part A: Patients must have either measurable or evaluable disease
* Part B: Patients must have measurable disease
* Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients must have a performance status corresponding to Easter Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age. Patients must have a Karnofsky or Lansky score \>= 50%
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
* Solid tumor patients: \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid. Patients with CNS tumors receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell Infusions (with or without total body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 30 days
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* Radiation therapy \[XRT\]/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, I-131 metaiodobenzylguanidine \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to CBL0137
* For patients with solid tumors without known bone marrow involvement:
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
* For patients with solid tumors without known bone marrow involvement:
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a creatinine based on age/sex as follows (performed within 7 days prior to enrollment unless otherwise indicated):
* Age: Maximum serum creatinine (mg/dL)
* 1 to \< 2 years: 0.6 (male); 0.6 (female)
* 2 to \< 6 years: 0.8 (male); 0.8 (female)
* 6 to \< 10 years: 1 (male); 1 (female)
* 10 to \< 13 years: 1.2 (male); 1.2 (female)
* 13 to \< 16 years: 1.5 (male); 1.4 (female)
* \>= 16 years: 1.7 (male); 1.4 (female)
* Patients with solid tumors:
* Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with solid tumors:
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (performed within 7 days prior to enrollment unless otherwise indicated)
* Shortening fraction of \>= 27% by echocardiogram (performed within 7 days prior to enrollment unless otherwise indicated) or
* Ejection fraction of \>= 50% by gated radionuclide study (performed within 7 days prior to enrollment unless otherwise indicated)
* Corrected QT (QTC) \< 480 msec (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with seizure disorder may be enrolled if seizures well controlled without the use of enzyme-inducing anti-convulsant agents. Well controlled is defined by no increase in seizure frequency in the prior 7 days
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5) resulting from prior therapy must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* Patients have consented to receive a central venous catheter prior to the administration of CBL0137. A central line is required for CBL0137 administration
Exclusion Criteria
* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* Patients who are receiving drugs that are strong inducers or inhibitors of CYP3A4, CYP2B6 (e.g., carbamazepine) and CYP1A2 (e.g., ciprofloxacin, enoxacin, fluvoxamine, smoking) are not eligible. These agents are to be avoided for 7 days prior to the start of CBL0137 and for the duration of the protocol therapy. Sensitive substrates of CYP2D6 (e.g., atomoxetine, desipramine, dextromethorphan, eliglustat, nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine) should also be avoided for the duration protocol therapy
* Patients who are receiving drugs associated with a known risk of Torsades de Pointes (TdP) are not eligible. Drugs associated with known risk of Torsades de Pointes (TdP) are to be avoided for 7 days prior to the start of CBL0137 and for duration of the protocol therapy
* Patients with known peripheral vascular disease are excluded
* Patients with a history of pro-thrombotic disorder are not eligible
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
12 Months
21 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Incuron LLC
UNKNOWN
Children's Oncology Group
NETWORK
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
David S Ziegler
Role: PRINCIPAL_INVESTIGATOR
Pediatric Early Phase Clinical Trial Network
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Children's Hospital of Alabama
Birmingham, Alabama, United States
Phoenix Childrens Hospital
Phoenix, Arizona, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital of Orange County
Orange, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
New York Medical College
Valhalla, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
Seattle Children's Hospital
Seattle, Washington, United States
Sydney Children's Hospital
Randwick, New South Wales, Australia
Countries
Review the countries where the study has at least one active or historical site.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2021-03150
Identifier Type: REGISTRY
Identifier Source: secondary_id
PEPN2111
Identifier Type: OTHER
Identifier Source: secondary_id
PEPN2111
Identifier Type: OTHER
Identifier Source: secondary_id
PEPN2111
Identifier Type: -
Identifier Source: org_study_id