A Phase 1/2 Trial of CBL0137 in Patients with Relapsed or Refractory Solid Tumors including CNS Tumors and Lymphoma
M
Melissa Bear, MD
Primary Investigator
Overview
We are conducting a pediatric phase 1 trial of single-agent intravenous CBL0137 given on Day 1 and Day 8 of a 21 day cycle in children with refractory or recurrent solid tumors, including CNS tumors and lymphoma. The study will use the rolling six design with the primary aim of determining the maximum-tolerated pediatric dose of CBL0137. The study will also assess the toxicity profile and determine the pharmacokinetics of CBL0137 in children with solid and CNS tumors. Once the Recommended Phase 2 Dose (RP2D) is established the study will include expansion cohorts in patients with recurrent/progressive DIPG and osteosarcoma to assess for signals of anti-tumor activity.
Eligibility
You may be eligible for this study if you meet the following criteria:
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Conditions:
relapsed solid tumors,refractory solid tumors,lymphoma,relapsed osteosarcoma,refractory osteosarcoma,Diffuse Intrinsic Pontine Glioma
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Age: Between 1 Years - 21 Years
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Gender: All
Inclusion Criteria:
- Age: -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.
- Diagnosis: 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 CSF or serum tumor markers including alphafetoprotein or beta-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
- Disease Status: Part A: Patients must have either measurable or evaluable disease (see Sections 12.2 and 12.3 for definitions).
Part B1 and B2: Patients must have measurable disease (Section 12.2).
- Therapeutic Options: 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.
- Performance Level: Patients must have a performance status corresponding to 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 Karnofsy or Lansky score > 50%. See https://www.cogmembers.org/site/pages/default.aspx?page=Prot_reference_ materials under Standard Sections for Protocols.
Exclusion Criteria:
- Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events 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.
- Concomitant Medications:
Corticosteroids: 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 (see Section 4.1.6.1.d).
Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.
Anti-cancer Agents: Patients who are currently receiving other anticancer agents are not eligible [except leukemia patients receiving
hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy]. 4.2.2.4 Anti-GVHD agents post-transplant:
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. 4.2.2.6 CYP-450 interactions: Patients who are receiving drugs that are strong inducers or inhibitors of CYP3A4
(Appendix III), 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. 4.2.2.7 QTc Agents: Patients who are receiving drugs that prolong
QTc are not eligible. QTc- prolonging drugs are to be avoided for 7 days prior to the start of CBL0137 and for duration of the protocol
therapy. See Appendix IV for a list of agents.
- 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
30 Apr 2024.
Study ID: 14269
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