Inclusion Criteria:

          -  Patients must have DIPG, as defined below, to be eligible for this protocol. Given the
             poor prognosis of all patients with DIPG, patients may enroll at any point in their
             disease course provided they have received standard radiation therapy (also defined
             below) and meet all other eligibility requirements.

          -  DIPG is defined, for this study, as a diffusely infiltrative lesion with the epicenter
             in the pons, involving at least 2/3 of the pons as assessed by T2 or FLAIR imaging,
             and with no major or primary exophytic component, OR a pontine-based lesion that is
             biopsy proven non-pilocytic, WHO II-IV glioma. H3K27M status will be assessed in
             patients when tissue is available, but patients are eligible regardless of H3K27M
             status. (Biopsy will NOT be performed as part of this study).

          -  Standard radiation therapy is defined, for this study, as 54-60 Gy standard focal
             (photon or proton) radiation therapy, administered over 6 weeks (+/- 10 days).
             Patients who receive standard radiation therapy with concurrent chemotherapy may be
             eligible as long as other criteria are met.

          -  Patients must be < 22 years of age at the time of enrollment.

          -  Patient must be able to swallow capsules whole.

          -  Karnofsky Performance Scale (KPS, for ≥ 16 years of age) or Lansky Performance Scale
             (LPS, for < 16 years of age) assessed within 7 days prior to treatment initiation must
             be ≥ 50%. Patients who are unable to walk because of neurologic deficits, but who are
             up and awake in a wheelchair, will be considered ambulatory for the purpose of
             assessing the performance score.

          -  Patients must have recovered (defined as < Grade 1 or baseline to meet otherwise
             defined eligibility criteria) from acute treatment-related toxicities of all prior
             chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

          -  Patients must have received their last fraction of radiation therapy at least 2 weeks
             prior to treatment initiation.

          -  Patients must have received their last dose of known myelosuppressive chemotherapy at
             least 21 days prior to enrollment (42 days if prior nitrosourea).

          -  Investigational/Biologic Agent/Immunotherapy (for agents that fit more than one
             category, i.e. biologic and immunotherapy, use the longest time-point indicated since
             last therapy to assess eligibility; contact PI or Study Chair if any questions):

               -  Patient must have recovered (< Grade 1) from any acute toxicity potentially
                  related to the agent and received their last dose of the investigational or
                  biologic agent ≥ 7 days prior to study enrollment.

                    -  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 and discussed with the principal
                       investigator.

               -  Monoclonal antibody treatment and agents with known prolonged half-lives: At
                  least three half-lives must have elapsed prior to enrollment due to the potential
                  risk of pseudoprogression.

               -  Checkpoint inhibitors, vaccine, or CAR T cell therapy: At least 3 months must
                  have elapsed from last treatment prior to enrollment due to the risk of
                  pseudo-progression.

               -  Convection Enhanced Delivery (CED)

                    -  Patients must be at least 4 weeks from last CED procedure, have no permanent
                       indwelling CED device, and no evidence of acute or ongoing intra-tumoral
                       hemorrhage as demonstrated by gradient echo MRI. Additionally, patients must
                       have recovered (< Grade 1) from any acute toxicity potentially related to
                       the infused agent or procedure.

               -  Intra-arterial therapy: Patient must be at least 4 weeks from most recent
                  procedure, regardless of chemotherapeutic agent(s) infused and no evidence of
                  acute or ongoing intratumoral hemorrhage as demonstrated by gradient echo MRI.
                  Additionally, patients must have recovered (< Grade 1) from any acute toxicity
                  potentially related to the infused agent or procedure.

               -  Information regarding any prior investigational therapy or procedure, including
                  (but not limited to) agent(s), dose, method of administration, dates of
                  administration, concomitant therapies, all toxicities reported to date and
                  anticipated toxicities, must be available for review by this study PI prior to
                  patient enrollment. This includes any investigational therapy, including (but not
                  limited to) those given in other countries or in private clinics.

        If information on an investigational therapy is unavailable or the PI cannot assess ongoing
        potential risk of a prior therapy, the patient is not eligible.

          -  Patients must have adequate organ and marrow function as defined below:

               -  Absolute neutrophil count (ANC) ≥ 1,000/mm3

               -  Platelets ≥ 100,000/ mm3 (unsupported, defined as no platelet transfusion within
                  7 days, and recovery from post-transfusion nadir)

               -  Hemoglobin (Hgb) ≥ 8 g/dL (may receive transfusions)

               -  Total bilirubin ≤ 2 times institutional upper limit of normal (ULN)

               -  ALT(SGPT) < 3 x institutional upper limit of normal

               -  Albumin ≥ 3 g/dL

               -  Potassium within institutional normal range

               -  Serum total calcium (correct for serum albumin) or ionized calcium within
                  institutional normal range

               -  Serum creatinine based on age/gender as noted in Table 2. Patients who do not
                  meet the criteria in the table but who have a 24-hour Creatinine Clearance or GFR
                  (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m2 are eligible.

                    -  Table 2: Serum Creatinine for age/sex Serum Creatinine for age/sex Age
                       Maximum Serum Creatinine (mg/dL) Male Female < 3 years < 0.8 < 0.8 3 to < 6
                       years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years
                       1.5 1.4

                         -  16 years 1.7 1.4 The threshold creatinine values in this Table were
                            derived from the Schwartz formula for estimating GFR(63) utilizing
                            child length and stature data published by the CDC.

               -  Left ventricular ejection fraction ≥ 50 by gated radionuclide study OR shortening
                  fraction of ≥ 27% by echocardiogram

               -  Patient must have a QTcF interval < 450 milliseconds (ms).

          -  Patients must be off all colony-forming growth factor(s) (i.e. filgrastim,
             sargramostim or erythropoietin) for at least 7 days prior to enrollment; 14 days must
             have elapsed if patients received PEG formulations.

          -  Patients must agree to avoid grapefruit or grapefruit juice and Seville (sour) oranges
             during the entire study as these are known to interfere with panobinostat
             pharmacokinetics.

          -  Pregnant and breastfeeding women are excluded from this study because marizomib and
             panobinostat's potential for teratogenic or abortifacient effects is unknown. Because
             there is an unknown but potential risk for adverse events in nursing infants secondary
             to treatment of the mother with marizomib or panobinostat, breastfeeding should be
             discontinued if the mother is treated with marizomib or panobinostat.

          -  The effects of marizomib and panobinostat on the developing human fetus are unknown.
             For this reason, women of child-bearing potential and men (including those who have
             had a vasectomy) must agree to use contraception (hormonal or barrier method of birth
             control; abstinence) prior to study entry and for the duration of study participation
             and up to 3 months for a female and 6 months for a male after the last dose of the
             drug (either marizomib or panobinostat, whichever is administered last). If you are
             able to become pregnant, you will have repeat pregnancy tests during the test. Should
             a woman become pregnant or suspect she is pregnant while she or her partner is
             participating in this study, she should inform her treating physician immediately.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Patients who have received > 60 Gy total radiation to the pons (e.g. patients who have
             received re-irradiation) due to potential increased risk of intratumoral hemorrhage

          -  Patients who have had prior bone marrow transplant or received marrow ablative therapy

          -  Patients with implanted CED catheters (e.g. Renshaw) due to inability to fully
             evaluate disease status

          -  Patients with a history of spinal radiation or those with an indication for acute
             spine radiation (e.g. significant cord compression) (Patients with leptomeningeal
             disease may be eligible but should be reviewed with study PI prior to enrollment).

          -  Patients with a history of disorientation, hallucinations or episodes of confusion
             (unless associated with a clear etiology, e.g. sedation, and fully resolved with no
             episodes in the 2 weeks prior to enrollment) since diagnosis of DIPG

          -  Patients with current or prior history of posterior reversible encephalopathy syndrome
             (PRES)

          -  Patients with significant (i.e. requiring active/ongoing treatment) GI dysfunction or
             GI disease, e.g. inflammatory bowel disease.

          -  Patients with chronic diarrhea or current diarrhea (≥ 4 stools/day).

          -  Patients with any clinically significant unrelated systemic illness (e.g. serious
             infections, mental illness, or significant cardiac, pulmonary, hepatic or other organ
             dysfunction), that, in the opinion of the investigator, would compromise the ability
             of the patient to tolerate protocol therapy or put them at additional risk for
             toxicity or would interfere with the study procedures, ability to assign attribution,
             or results.

          -  Any ventricular arrhythmias with the exception of benign premature ventricular
             contractions

          -  Patients known to be refractory to red blood cell or platelet transfusions. Patients
             who are receiving any other anticancer or investigational drug therapy

          -  Patients who are required to receive any medication listed in Appendix B or is
             otherwise known to significantly prolong the QTc interval. (Note: Loperamide use is
             acceptable at doses no higher than listed in this protocol).

          -  Patients who are taking cannabinoids, cannabinoid oils, any psychoactive supplement,
             narcotics, or any agent that can potentially cause hallucinations, disorientation,
             confusion or dizziness

          -  Patients/parents/caregivers must disclose all supplements and/or alternative therapies
             being administered to the patient. If unwilling or unable, patient is not eligible.

          -  Patients receiving enzyme-inducing antiepileptic drugs and/or valproic acid. Patients
             are eligible if they discontinue enzyme-inducing antiepileptic drugs and/or valproic
             acid prior to enrollment and have a washout period of least 5 half-lives.

          -  Patients who, in the opinion of the investigator, are unwilling or unable to return
             for required follow-up visits or obtain follow-up studies required to assess toxicity
             to therapy or to adhere to drug administration plan, other study procedures, and study
             restrictions

          -  Known or suspected hypersensitivity to marizomib or panobinostat

          -  Any patient who has the potential to receive a marizomib dose less than 0.2 mg