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.
PRIMARY OBJECTIVES: 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
63
Undergo collection of blood samples
Undergo bone marrow aspirate
Undergo bone marrow biopsy
Undergo ECHO
Given IV
Children's Hospital of Alabama
Birmingham, Alabama, United States
RECRUITINGPhoenix Childrens Hospital
Phoenix, Arizona, United States
RECRUITINGChildren's Hospital Los Angeles
Los Angeles, California, United States
RECRUITINGChildren's Hospital of Orange County
Orange, California, United States
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
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
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
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
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
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
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UCSF Medical Center-Mission Bay
San Francisco, California, United States
RECRUITINGChildren's Hospital Colorado
Aurora, Colorado, United States
RECRUITINGChildren's National Medical Center
Washington D.C., District of Columbia, United States
RECRUITINGJohns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
RECRUITINGChildren's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, United States
RECRUITINGLurie Children's Hospital-Chicago
Chicago, Illinois, United States
RECRUITING...and 24 more locations