OverviewStudy detailsEligibilityThings to knowResearchStudy plan
info
Simplify with AI

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

PHASE1PHASE2RECRUITING

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.

Study details:

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.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Patients must be >= 12 months and <= 21 years of age at the time of study enrollment
  2. 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)
  3. 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
  4. 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
  5. Part A: Patients must have either measurable or evaluable disease
  6. Part B: Patients must have measurable disease
  7. 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
  8. 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%
  9. 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.
  10. 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)
  11. 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)
  12. 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)
  13. 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)
  14. 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)
  15. 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)
  16. Corrected QT (QTC) < 480 msec (performed within 7 days prior to enrollment unless otherwise indicated)
  17. 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
  18. 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
  19. 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

  1. 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
  2. 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
  3. Patients who are currently receiving another investigational drug are not eligible
  4. 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)
  5. 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
  6. 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
  7. 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
  8. Patients with known peripheral vascular disease are excluded
  9. Patients with a history of pro-thrombotic disorder are not eligible
  10. Patients who have an uncontrolled infection are not eligible
  11. Patients who have received a prior solid organ transplantation are not eligible
  12. 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

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE1PHASE2

trial

Study ID

NCT04870944

Intervention or treatment

PROCEDURE: Biospecimen Collection

PROCEDURE: Bone Marrow Aspirate

PROCEDURE: Bone Marrow Biopsy

PROCEDURE: Echocardiography Test

DRUG: FACT Complex-targeting Curaxin CBL0137

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

  • Condition: Diffuse Midline Glioma, H3 K27-Altered, Metastatic Malignant Neoplasm in the Central Nervous System and more

  • PROCEDURE: Biospecimen Collection and other drugs

  • Randwick, New South Wales, Australia

  • Sponsor: Children's Oncology Group

Save

Share

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Sydney Children's Hospital

Select from list below to view details:

  • Sydney Children's Hospital

    Randwick, New South Wales, Australia

Loading map...

Who is running the clinical trial?

COG

Children's Oncology Group

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
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.
Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspirate, Procedure: Bone Marrow Biopsy, Procedure: Echocardiography Test, Drug: FACT Complex-targeting Curaxin CBL0137

    What is the study measuring?

    Primary Outcome

    MeasureDescriptionTime Frame
    Maximum tolerated dose and/or Recommended Phase 2 dose of CBL0137Maximum 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 Outcome

    MeasureDescriptionTime Frame
    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.Up to 4 months
    Frequency of adverse events attributable to CBL0137The frequency (%) of patients experiencing adverse events that are at least possibly attributable to CBL0137 by study part and dose level.Up to 60 months
    Area under the drug concentration curve of CBL0137The median (min, max) of the area under the drug concentration curve for CBL0137 by study part and dose level.Up to 3 days
    Are you running this trial?If you're a clinic or sponsor, you can claim this study.
    Claim this trial

    References

    Clinical Trials Gov: CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma

    Other trials to consider

    Loading suggested trials...

    Top searched conditions

    Breast CancerLung CancerType 2 DiabetesDermatitisAlzheimersParkinsonsLupusCrohn’s DiseaseAsthmaHypertensionCOPDMultiple SclerosisOsteoarthritisHIV/AIDSPsoriasisStrokeObesityProstate CancerDepressionCardiovascular