Why are we doing this research?
This pilot study is designed to assess the safety, tolerability, and preliminary anti-tumor activity of the combination of pembrolizumab, decitabine and fixed-dose hypofractionated index site radiotherapy in pediatric and young adult patients with relapsed, refractory or progressive non-primary CNS solid tumors and lymphomas.
- Patients will receive pembrolizumab and decitabine every 28 days, and a single 3 day course of fixed-dose hypofractionated index site radiotherapy.
- One cycle lasts 28 days. One block lasts 84 days (3 cycles per block). Radiation is given in block 1 only (cycle 2 only). Blocks may repeat for a total of 9 times (27 cycles) if patient meets criteria to continue protocol therapy.
Study Type: Interventional
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
Who can participate?
AGES ELIGIBLE FOR STUDY: 12 Months up to 40 Years
- Age: greater than or equal to 12 months and less than or equal to 40 years.
- Diagnosis: Patients must have had histologic verification of malignancy at original diagnosis or relapse. Eligible diagnoses include:
- Relapsed or refractory solid tumors (excluding primary CNS tumors)
- Lymphoma in second or greater relapse or with refractory disease
- Disease Evaluation: Patients must have evaluable or measurable disease (patients with evaluable disease must have a lesion that is amenable to radiation as below).
- Patients with stable non-brainstem CNS metastases may be eligible.
- 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: Lansky/Karnofsky greater than or equal to 50%.
- Prior Therapy: Patients who have previously received inhibitors of PD-1, PD-L1, CTLA4 or other immune checkpoint inhibitors, regardless of response, are eligible as long as they had not experienced a medically significant immune related adverse event that required treatment with supraphysiologic steroids or other immunomodulatory drug.
- Patients must have recovered from the acute toxic effects of all prior anti-cancer chemotherapy and meet the following:
- Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
- Hematopoietic growth factors: At least 21 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor.
- Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent.
- Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.
- Monoclonal antibodies: At least 4 weeks after the last dose of a monoclonal antibody.
- XRT: At least 14 days after local palliative XRT (limited field); At least 150 days must have elapsed if prior TBI, craniospinal XRT or radiation treatment resulting in greater than or equal to 50% of the pelvis receiving greater than or equal to 10 Gy.
- Stem Cell Infusion without TBI: At least 84 days must have elapsed after autologous stem cell transplant or stem cell infusion. Patients having received allogeneic stem cells are not eligible.
- Adequate Bone Marrow Function Defined as:
- Peripheral absolute neutrophil count (ANC) greater than or equal to 750/mm3
- Platelet count greater than or equal to 75,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- Hemoglobin greater than or equal to 8 (transfusions allowed)
- Patients with known bone marrow involvement will be eligible for the study provided that they have a platelet count of greater than or equal to 50,000/mm3 (transfusion independent, defined as not receiving platelet transfusion for at least 7 days prior to enrollment).
- Adequate Renal Function Defined as:
- Creatinine clearance, cystatin C based GFR, or radioisotope GFR greater than or equal to 70ml/min/1.73 m2 or a serum creatinine based on protocol requirements.
- Adequate Liver Function Defined as:
- Direct bilirubin less than or equal to 1.5 x upper limit of normal (ULN) for age
- SGPT (ALT) less than or equal to 3.0 x upper limit of normal (ULN). For patients with known liver metastases or primary tumor, SGPT (ALT) less than or equal to 5 x upper limit of normal (ULN) may be accepted. For the purposes of this study, the ULN of SGPT is 45 U/L.
- Adequate Cardiac Function Defined as:
- Ejection fraction of greater than or equal to 50% by echocardiogram (3D if available) or cardiac MRI.
- QTC less than or equal to 480 msec.
- Adequate Pulmonary Function Defined as:
- Pulse oximetry greater than 94% on room air and no dyspnea at rest.
- Radiation Considerations:
- Patients must have at least one non-CNS lesion amenable to radiation as defined in the protocol and at the discretion of the PIs.
- Patients with previously irradiated sites of disease may be considered eligible if potential index site lesions meet the following: There has been documented progression at that site (by RECIST or for neuroblastoma patients enrolled with evaluable disease, persistent MIBG avidity), and Re-irradiation would not expose the patient to a substantial increase in toxicity (as determined by consultation with co-principal investigator or designee and treating oncologist).
- Patients with primary CNS tumors, brainstem metastases, and/or carcinomatous meningitis are not eligible.
- Pregnant or breast-feeding women will not be entered on this study.
- Corticosteroids and other immunosuppressive therapy: Patients requiring systemic corticosteroids or other immunosuppressive medication within 7 days prior to enrollment are not eligible with the exception of physiologic replacement doses of corticosteroids.
- Patients who are currently receiving another investigational drug are not eligible.
- Patients who are currently receiving other anti-cancer agents are not eligible.
- Patients with a history of an autoimmune disorder are not eligible. Asymptomatic laboratory abnormalities (e.g. ANA, rheumatoid factor) will not render a patient ineligible in the absence of a diagnosis of an autoimmune disorder.
- Patients with known hepatitis B (HBsAg reactive) or C (HCV RNA -qualitative is detected) are excluded.
- Patients with HIV are excluded if they have detectable viral loads or CD4 count is below 400 or they are not compliant with antiretroviral agents.
- Patients who have an uncontrolled infection are not eligible.
- Patients with immunodeficiency syndromes are not eligible.
- Patients with a history of clinically significant cardiac disease are not eligible.
- Patients with ongoing interstitial lung disease or pneumonitis are not eligible.
- Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).
- Patients who have received a live vaccine less than or equal to 30 days prior to enrollment are ineligible.
- Patients who have received a prior solid organ transplant at any time, or allogeneic bone marrow transplantation within the past 5 years (or have signs or symptoms of GVHD) 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.