Pembrolizumab in Combination With Decitabine and Hypofractionated Index Lesion Radiation in Pediatrics and Young Adults

NCT03445858 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: Pembro_BT_1603
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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. Primary Objectives

• To determine the feasibility of administering pembrolizumab in combination with decitabine and hypofractionated index lesion radiation
• To identify the treatment related toxicity and tolerability of the combination of decitabine and pembrolizumab with hypofractionated index lesion radiation Secondary Objective To preliminarily define the anti-tumor efficacy of the combination of pembrolizumab, decitabine and hypofractionated index lesion radiation in patients with relapsed, refractory, or progressive non-CNS solid tumors and lymphomas using overall response rate (CR + PR) by irRECIST after 2 cycles of therapy. Exploratory Objectives To profile the kinetics of the immune response and to correlate with promotor methylation changes, nuclear imaging, stool microbiota diversity, and tumor associated antigen immune responses.

Conditions

Childhood Solid Tumor; Relapsed Cancer; Adult Lymphoma; Childhood Lymphoma; Refractory Cancer; Adult Solid Tumor

Keywords

Pediatric; Immunotherapy; Radiation; Radiotherapy; PD-1; Decitabine; DNMT; Epigenetic; Solid Tumor; Saroma; Lymphoma; Checkpoint; Abscopal; Cancer; Immune; SBRT

Outcome Measures

Primary Outcomes (1)

• Feasibility of administering Pembrolizumab in combination with Decitabine and hypofractionated index radiation

  Incidence of number of patients who experience a DLT

  Days 1 thru 57

Secondary Outcomes (2)

• Identification of treatment related toxicities and tolerability

  Days 1 thru 57

• Define anti-tumor efficacy of treatment combination of pembrolizumab, decitabine, and hypofractionated index radiation (per irRECIST criteria)

  2 cycles (56 days)

Study Arms (1)

Pembrolizumab, Decitabine, Radiation

EXPERIMENTAL

Patients will receive pembrolizumab and decitabine every 28 days, and a single 3 day course of fixed-dose hypofractionated radiotherapy to one or more index lesions.

Drug: Pembrolizumab; Drug: Decitabine; Radiation: Hypofractionated Index Site Radiation

Interventions

Decitabine DRUG

Patients will receive decitabine every 28 days.One cycle lasts 28 days. Cycles may repeat for a total of 26 cycles if patient meets criteria to continue protocol therapy.

Also known as: Dacogen

Pembrolizumab, Decitabine, Radiation

Hypofractionated Index Site Radiation RADIATION

Patients will receive a single 3 day course of fixed-dose hypofractionated radiotherapy to one or more index lesions during the first cycle only.

Pembrolizumab, Decitabine, Radiation

Pembrolizumab DRUG

Patients will receive pembrolizumab every 28 days.One cycle lasts 28 days. Cycles may repeat for a total of 26 cycles if patient meets criteria to continue protocol therapy.

Also known as: Keytruda

Pembrolizumab, Decitabine, Radiation

Eligibility Criteria

• Age: 12 Months - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 at least one 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.

You may not qualify if:

• 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 a non-thyroiditis 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. Autoimmune thyroiditis will not render a patient ineligible.
• 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.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Recurrence; Neoplasms; Lymphoma

Interventions

pembrolizumab; Decitabine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Brian Turpin, DO

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: February 26, 2018
• Study Start: February 12, 2018
• Primary Completion: November 7, 2023
• Study Completion: November 7, 2023
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

US (1)