Recruiting

Phase 1

Phase 2

CBL0137CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma

Sponsor:

Children's Oncology Group

Code:

NCT04870944

Conditions

Diffuse Midline Glioma, H3 K27-Altered

Metastatic Malignant Neoplasm in the Central Nervous System

Recurrent Diffuse Intrinsic Pontine Glioma

Recurrent Diffuse Midline Glioma, H3 K27-Altered

Recurrent Lymphoma

Eligibility Criteria

Sex: All

Age: 1 - 21

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Bone Marrow Aspirate

Bone Marrow Biopsy

Echocardiography Test

FACT Complex-targeting Curaxin CBL0137

Study Details

Brief summary:

This phase I/II trial evaluates the best dose, side effects and possible benefit of CBL0137 in treating patients with solid tumors, including central nervous system (CNS) tumors or lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Drugs, such as CBL0137, block signals passed from one molecule to another inside a cell. Blocking these signals can affect many functions of the cell, including cell division and cell death, and may kill cancer cells.

Conditions

Diffuse Midline Glioma, H3 K27-Altered

Metastatic Malignant Neoplasm in the Central Nervous System

Recurrent Diffuse Intrinsic Pontine Glioma

Recurrent Diffuse Midline Glioma, H3 K27-Altered

Recurrent Lymphoma

Study ID

NCT04870944

Start date

Jan 28, 2022

Status verified date

Sep, 2026

Completion date

Dec 31, 2026

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 1 - 21

Healthy Volunteers: Not accepted

Inclusion Criteria:

Parts A and B: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
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:

Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
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

Study Design

Enrollment

63 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

Interventions

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

Primary outcome measure

Maximum tolerated dose and/or Recommended Phase 2 dose of CBL0137 [ Time Frame: Up to 21 days ]
Frequency of dose limiting toxicities of CBL0137 (Phase I) [ Time Frame: Up to 21 days ]
Anti-tumor effect of CBL0137 in children with diffuse intrinsic pontine glioma (DIPG) or other H3 K27-altered diffuse midline gliomas (Phase II) [ Time Frame: Up to 4 months ]

Central Contacts and Locations

Locations

Children's Hospital of Alabama

Recruiting

Birmingham, Alabama, United States, 35233

Contacts

Site Public Contact

205-638-9285 oncologyresearch@peds.uab.edu

Principal Investigator:

Girish Dhall

Phoenix Childrens Hospital

Recruiting

Phoenix, Arizona, United States, 85016

Contacts

Site Public Contact

602-546-0920

Principal Investigator:

Alok K. Kothari

Children's Hospital Los Angeles

Recruiting

Los Angeles, California, United States, 90027

Contacts

Site Public Contact

323-361-4110

Principal Investigator:

Fariba Navid

Children's Hospital of Orange County

Recruiting

Orange, California, United States, 92868

Contacts

Site Public Contact

714-509-8646 oncresearch@choc.org

Principal Investigator:

Elyssa M. Rubin

UCSF Medical Center-Mission Bay

Recruiting

San Francisco, California, United States, 94158

Contacts

Site Public Contact

877-827-3222 cancertrials@ucsf.edu

Principal Investigator:

Kieuhoa T. Vo

Children's Hospital Colorado

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Site Public Contact

303-764-5056 josh.b.gordon@nsmtp.kp.org

Principal Investigator:

Margaret E. Macy

Children's National Medical Center

Recruiting

Washington D.C., District of Columbia, United States, 20010

Contacts

Site Public Contact

202-476-2800 OncCRC_OnCall@childrensnational.org

Principal Investigator:

AeRang Kim

Johns Hopkins All Children's Hospital

Recruiting

St. Petersburg, Florida, United States, 33701

Contacts

Site Public Contact

727-767-4784 Ashley.Repp@jhmi.edu

Principal Investigator:

Jonathan L. Metts

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Recruiting

Atlanta, Georgia, United States, 30329

Contacts

Site Public Contact

404-785-0232 Olivia.Floyd@choa.org

Principal Investigator:

Jason R. Fangusaro

Lurie Children's Hospital-Chicago

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Site Public Contact

773-880-4562

Principal Investigator:

Elizabeth A. Sokol

University of Chicago Comprehensive Cancer Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Site Public Contact

773-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Ami V. Desai

Riley Hospital for Children

Recruiting

Indianapolis, Indiana, United States, 46202

Contacts

Site Public Contact

800-248-1199

Principal Investigator:

Brian D. Weiss

Johns Hopkins University/Sidney Kimmel Cancer Center

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Site Public Contact

410-955-8804 jhcccro@jhmi.edu

Principal Investigator:

Christine A. Pratilas

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Site Public Contact

877-442-3324

Principal Investigator:

Steven G. DuBois

C S Mott Children's Hospital

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Site Public Contact

800-865-1125

Principal Investigator:

Rajen Mody

University of Minnesota/Masonic Cancer Center

Recruiting

Minneapolis, Minnesota, United States, 55455

Contacts

Site Public Contact

612-624-2620

Principal Investigator:

Robin L. Williams

Children's Mercy Hospitals and Clinics

Recruiting

Kansas City, Missouri, United States, 64108

Contacts

Site Public Contact

816-302-6808 COGResearchGroup@cmh.edu

Principal Investigator:

Kevin F. Ginn

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Site Public Contact

800-600-3606 info@siteman.wustl.edu

Principal Investigator:

Shalini Shenoy

Roswell Park Cancer Institute

Recruiting

Buffalo, New York, United States, 14263

Contacts

Site Public Contact

800-767-9355 askroswell@roswellpark.org

Principal Investigator:

Clare J. Twist

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

Recruiting

New York, New York, United States, 10032

Contacts

Site Public Contact

212-342-5162 cancerclinicaltrials@cumc.columbia.edu

Principal Investigator:

Nobuko Hijiya

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Julia L. Glade Bender

New York Medical College

Recruiting

Valhalla, New York, United States, 10595

Contacts

Site Public Contact

914-594-3794

Principal Investigator:

Mitchell S. Cairo

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Site Public Contact

888-275-3853

Principal Investigator:

Jessica M. Sun

Cincinnati Children's Hospital Medical Center

Recruiting

Cincinnati, Ohio, United States, 45229

Contacts

Site Public Contact

513-636-2799 cancer@cchmc.org

Principal Investigator:

Joseph G. Pressey

Oregon Health and Science University

Recruiting

Portland, Oregon, United States, 97239

Contacts

Site Public Contact

503-494-1080 trials@ohsu.edu

Principal Investigator:

Bill H. Chang

Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Site Public Contact

267-425-5544 CancerTrials@email.chop.edu

Principal Investigator:

Theodore W. Laetsch

Children's Hospital of Pittsburgh of UPMC

Recruiting

Pittsburgh, Pennsylvania, United States, 15224

Contacts

Site Public Contact

412-692-8570 jean.tersak@chp.edu

Principal Investigator:

Andrew Bukowinski

Saint Jude Children's Research Hospital

Recruiting

Memphis, Tennessee, United States, 38105

Contacts

Site Public Contact

888-226-4343 referralinfo@stjude.org

Principal Investigator:

Dana Tlais

UT Southwestern/Simmons Cancer Center-Dallas

Recruiting

Dallas, Texas, United States, 75390

Contacts

Site Public Contact

214-648-7097 canceranswerline@UTSouthwestern.edu

Principal Investigator:

Laura J. Klesse

Cook Children's Medical Center

Recruiting

Fort Worth, Texas, United States, 76104

Contacts

Site Public Contact

682-885-2103 CookChildrensResearch@cookchildrens.org

Principal Investigator:

Sibo Zhao

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Site Public Contact

713-798-1354 burton@bcm.edu

Principal Investigator:

Jennifer H. Foster

Primary Children's Hospital

Recruiting

Salt Lake City, Utah, United States, 84113

Contacts

Site Public Contact

801-585-5270

Principal Investigator:

Matthew Dietz

Children's Hospital of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

Contacts

Site Public Contact

414-955-4727 MACCCTO@mcw.edu

Principal Investigator:

Sarah Rumler

More Information

Sponsor

Children's Oncology Group

Last update posted

Sep 11, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-12. This information was provided to ClinicalTrials.gov by Children's Oncology Group on 2026-09-11.