Health TrialsbyHealthPanel

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

ConditionsDiffuse Midline Glioma, H3 K27-AlteredMetastatic Malignant Neoplasm in the Central Nervous SystemRecurrent Diffuse Intrinsic Pontine GliomaRecurrent Diffuse Midline Glioma, H3 K27-AlteredRecurrent LymphomaRecurrent Malignant Solid NeoplasmRecurrent Primary Malignant Central Nervous System NeoplasmRefractory LymphomaRefractory Malignant Solid NeoplasmRefractory Primary Malignant Central Nervous System Neoplasm
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age12-21
SponsorChildren's Oncology Group

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Single group

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood samples

  • Bone Marrow Aspirate

    Procedure/Surgery

    Undergo bone marrow aspirate

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy

  • Echocardiography Test

    Procedure/Surgery

    Undergo ECHO

  • FACT Complex-targeting Curaxin CBL0137

    Drug

    Given IV

Treatment groups

63 Participants
are divided into 1 treatment group
Group A: Treatment (CBL0137)Experimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Up to 21 days
2

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.

Time frame
Up to 21 days
3

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).

Time frame
Up to 4 months

Secondary outcomes

1

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

Frequency (%) of patients with at least partial response to CBL0137 at the MTD/RP2D in children with refractory solid tumors and other central nervous system (CNS) tumors.

Time frame
Up to 4 months
2

Frequency of adverse events attributable to CBL0137

The frequency (%) of patients experiencing adverse events that are at least possibly attributable to CBL0137 by study part and dose level.

Time frame
Up to 60 months
3

Area under the drug concentration curve of CBL0137

The median (min, max) of the area under the drug concentration curve for CBL0137 by study part and dose level.

Time frame
Up to 3 days

Other outcomes

1

FACT in tumor specimens

A descriptive analysis of biomarkers will assess associations with disease response. The parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). All these analyses will be descriptive and exploratory and hypotheses generating in nature. FACT expression in tumor specimens will be determined by immunohistochemistry.

Time frame
Up to 60 months
2

Immune response

Will measure effects on the interferon response pathway. A descriptive analysis of biomarkers will assess associations with disease response. The parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). All these analyses will be descriptive and exploratory and hypotheses generating in nature. Peripheral blood lymphocytes will be assessed for expression of genes in the interferon response pathway, in order to determine whether treatment with CBL0137 leads to increase gene expression.

Time frame
Up to 60 months
3

Overall survival

Will be compared with historical controls in children with DIPG or other diffuse midline gliomas, H3 K27-altered.

Time frame
Up to 60 months
4

Progression-free survival

An exploratory analysis of progression-free survival using Kaplan-Meier curves and the log-rank test statistic will compare overall time-to-disease progression (or death) versus historical cohort for the DIPG cohort.

Time frame
Up to 60 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Children's Oncology Group

Lead sponsor

Incuron LLC

Collaborator

Source ClinicalTrials.gov
Apply now