CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma

NCT04870944 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: PEPN2111NCI-2021-03150UM1CA228823
• Study Type: interventional
• Target: 63
• Locations: 2 countries
• Sites: 35

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

Recurrent Lymphoma; 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 Malignant Solid Neoplasm; Recurrent Primary Malignant Central Nervous System Neoplasm; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Primary Malignant Central Nervous System Neoplasm

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose and/or Recommended Phase 2 dose of CBL0137

  Maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of CBL0137 in children with relapsed or refractory solid tumors including central nervous system (CNS) tumors and lymphoma.

  Up to 21 days

• Frequency of dose limiting toxicities of CBL0137 (Phase I)

  The frequency (%) of patients experiencing a cycle 1 dose limiting toxicity attributable to CBL0137 by study part and dose level.

  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)

  Frequency (%) of patients with at least partial response to CBL0137 at the maximum tolerated dose/recommended phase II dose (MTD/RP2D) in children with progressive or recurrent diffuse intrinsic pontine glioma (DIPG).

  Up to 4 months

Secondary Outcomes (3)

• Anti-tumor effect of CBL0137 in children with solid tumors (Phase I)

  Up to 4 months

• Frequency of adverse events attributable to CBL0137

  Up to 60 months

• Area under the drug concentration curve of CBL0137

  Up to 3 days

Other Outcomes (4)

• FACT in tumor specimens

  Up to 60 months

• Immune response

  Up to 60 months

• Overall survival

  Up to 60 months

Study Arms (1)

Treatment (CBL0137)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspirate; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography Test; Drug: FACT Complex-targeting Curaxin CBL0137

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (CBL0137)

Bone Marrow Aspirate PROCEDURE

Undergo bone marrow aspirate

Also known as: BONE MARROW, LIQUID, Human Bone Marrow Aspirate

Treatment (CBL0137)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (CBL0137)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (CBL0137)

FACT Complex-targeting Curaxin CBL0137 DRUG

Given IV

Also known as: CBL0137

Treatment (CBL0137)

Eligibility Criteria

• Age: 12 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Oncology Group: lead
• Incuron LLC: collaborator

Study Sites (35)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Children's National Medical Center

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

RECRUITING

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

RECRUITING

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

RECRUITING

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

RECRUITING

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

RECRUITING

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

RECRUITING

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

RECRUITING

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

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

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

New York Medical College

Valhalla, New York, 10595, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

RECRUITING

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

RECRUITING

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

SUSPENDED

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Lymphoma

Interventions

Specimen Handling; Fluid Therapy; Biopsy; CBLC137

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Drug Therapy; Therapeutics; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• David S Ziegler

  Pediatric Early Phase Clinical Trial Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: May 4, 2021
• Study Start: January 28, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 5, 2026

Record last verified: 2025-09

Locations

US (34); AU (1)