Inclusion Criteria:

• Patients must meet ALL the following criteria to be eligible for this study:
• 1. Age \< 22 years of age
• 2. Diagnosis of recurrent or refractory malignancy with histologic verification of malignancy at original diagnosis or relapse, except patients with extra-cranial germ-cell tumors who have elevations of serum tumor markers including alpha-fetoprotein or beta-HCG, and/or patients with intrinsic brain stem tumors or patients with CNS-germ cell tumors and elevations of CSF or serum tumor markers including alpha-fetoprotein or beta-HCG.
• 3. Have either measurable or evaluable disease. Evaluable disease is defined as an assessment of tumor that cannot be measured using a ruler or calipers, but can be used to determine disease progression or response (e.g., positive lesions on MIBG or bone scan, metastatic bone marrow disease, elevated tumor markers, or presence of a malignant pleural effusion)
• 4. Have current disease state for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• 5. Have Performance Level: Karnofsky ≥ 50% for patients \>16 years of age and Lansky ≥50 for patients ≤16 years of age
• 6. Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment. Patients with CNS tumors who are receiving steroids must be on a stable or decreasing dose for at least 7 days prior to study entry. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• 7. Have fully recovered from the acute clinically significant toxic effects of prior anti-cancer therapy
• * Myelosuppressive chemotherapy: On first day of treatment be at least 7 days after the last dose of myelosuppressive chemotherapy for single agent 9 ING 41, at least 21 days after the last dose of myelosuppressive chemotherapy for 9-ING-41 plus irinotecan
• * Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor or 7 days for short-acting growth factor
• * Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent.
• * Monoclonal antibodies: At least 28 days after the last dose of a monoclonal antibody
• * At least 14 days after local palliative XRT (small port); At least 100 days must have elapsed if prior TBI, craniospinal XRT or if ≥ 50% radiation of pelvis; At least 42 days must have elapsed if other substantial BM radiation
• * Stem Cell Infusion without TBI: No evidence of active graft versus host disease and at least 84 days must have elapsed after transplant or stem cell infusion.
• * Patients undergoing a major surgical procedure or laparoscopic procedure are eligible for enrollment after at least 28 days of the procedure, 14 days after an open biopsy.
• * Patients undergoing a major surgical procedure, laparoscopic procedure or open biopsy are eligible for enrollment after at least 28 days of the procedure
• * Central line placement or subcutaneous port placement is not considered major surgery.
• * Core biopsy within 7 days prior to enrollment
• * Fine needle aspirate within 7 days prior to enrollment
• * Surgical or other wounds must be adequately healed prior to enrollment
• 8. Have received at least one front line treatment regimen for the treatment of their malignancy - on the Irinotecan combination arm, patients may have received prior Irinotecan
• 9. Have adequate organ and marrow function on first day of study treatment as follows:
• * For single agent 9-ING-41: ANC ≥ 500/mm3 For 9-ING-41 plus Irinotecan: ANC ≥ 1000/mm3
• * For single agent 9-ING-41: Platelets ≥ 50,000/mm3 For 9-ING-41 plus Irinotecan: Platelets ≥ 100,000/mm3
• * Hemoglobin ≥ 8 g/dL
• * Bilirubin ≤ 1.5 mg/dL
• * Alanine aminotransferase (ALT) ≤ 5.0 x upper limit of normal (ULN) unless elevation considered due to disease
• * Aspartate transaminase (AST) ≤ 5.0 x ULN unless elevation considered due to disease
• * Serum amylase and lipase ≤ 1.5 x ULN unless elevation considered due to disease
• * Creatinine clearance or radioisotope GFR ≥ 70 ml/min/1.73m2 or a serum creatinine based on age/gender as follows:
• Age Maximum Serum Creatinine (mg/dL) Maximum Serum Creatinine (mg/dL) Male Female 1 month to \<6 months 0.4 0.4 6 months to \<1 year 0.5 0.5 1 to \<2 years 0.6 0.6 2 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
• 10. Pregnancy tests must be obtained in girls who are post-menarchal. Girls of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first study therapy. Patients of childbearing potential must agree to use hormonal or barrier birth control with spermicidal gel, or total abstinence to avoid pregnancy for the duration of study participation and in the following 100 days after discontinuation of study treatment (see Section 4.1.1).
• 11. All patients and/or their parents or legal guardians must sign a written informed consent. The investigational nature and objectives of the trial, the procedures and treatments involved and their attendant risks and discomforts, and potential alternative therapies will be carefully explained to the patient or the patient's parents or guardian if the patient is a child, and a signed informed consent and assent will be obtained according to institutional guidelines

Exclusion Criteria:

• Patients who meet any of the following criteria will be excluded from trial entry:
• 1. Has hypersensitivity to any of the components of 9-ING-41 and/or Irinotecan or to the excipients used in their formulation
• 2. Has uncontrolled concurrent illness that would limit compliance with study requirements
• 3. Has clinically significant retinal disease
• 4. Has current malignancy other than the target malignancy with the exception of surgically treated local tumors or is currently receiving other anti-cancer therapies, including radiation.
• 5. Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia, infertility and ototoxicity. Recovery is defined as ≤ Grade 2 severity per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5.0)
• 6. Is pregnant or lactating
• 7. Has received a prior solid organ transplantation
• 8. Is receiving any other investigational medicinal product or participating in another interventional clinical trial