A Phase 1/2 Trial of CBL0137 in Patients with Relapsed or Refractory Solid Tumors including CNS Tumors and Lymphoma

B
Brian Weiss

Primary Investigator

Enrolling By Invitation
1-21 years
All
Phase N/A
1 participants needed
3 Locations

Brief description of study

What is the purpose of this study?
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.

THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic.

Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

What will happen during the study?
  • 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 also undergo bone marrow aspirate and/or biopsy at baseline, echocardiograph (ECHO) prior to cycle 1, and as clinically indicated undergo collection of blood samples throughout the trial.
  • After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48 and 60 months.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Riley, relapsed solid tumors,refractory solid tumors,lymphoma,relapsed osteosarcoma,refractory osteosarcoma,Diffuse Intrinsic Pontine Glioma
  • Age: Between 1 Years - 21 Years
  • Gender: All

Inclusion Criteria:
    Parts A and B1: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
    Part B2 (relapsed/refractory osteosarcoma): Patients must be >= 12 months and =< 30 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 B1: Patients with progressive or recurrent DIPG (diagnosed by biopsy or imaging characteristics) and other H3 K27M-mutant diffuse midline gliomas previously treated with radiation therapy
        Part B2: Patients with relapsed or refractory osteosarcoma
    Part A: Patients must have either measurable or evaluable disease
    Part B1 and B2: 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/gender 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)
    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

Updated on 14 Sep 2024. Study ID: PHO-COG-PEPN2111, 14269, TX11478
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