Clinical Trials /

Durvalumab and Tremelimumab for Pediatric Malignancies

NCT03837899

Description:

The purpose of the study is to determine the recommended dose of durvalumab and tremelimumab (immunotherapy drugs) in pediatric patients with advanced solid and hematological cancers and expand in a second phase to test the efficacy of these drugs once this dose is determined.

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
  • Hodgkin Lymphoma
  • Lymphoma
  • Malignant Solid Tumor
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab and Tremelimumab for Pediatric Malignancies
  • Official Title: Phase I/II, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Durvalumab Monotherapy or in Combination With Tremelimumab in Pediatric Patients With Advanced Solid Tumors and Hematological Malignancies

Clinical Trial IDs

  • ORG STUDY ID: D419EC00001
  • NCT ID: NCT03837899

Conditions

  • Pediatric Cancer
  • Solid Tumor Pediatric
  • Hematological Malignancies

Interventions

DrugSynonymsArms
Durvalumab / Tremelimumab Combination Therapydurvalumab: Imfinzi, MEDI4736, tremelimumab: CP-675,206Durvalumab / Tremelimumab Combination Therapy

Purpose

The purpose of the study is to determine the recommended dose of durvalumab and tremelimumab (immunotherapy drugs) in pediatric patients with advanced solid and hematological cancers and expand in a second phase to test the efficacy of these drugs once this dose is determined.

Detailed Description

      This is a first time in pediatrics study primarily designed to evaluate the safety and
      tolerability of durvalumab and durvalumab in combination with tremelimumab at increasing
      doses in pediatric patients with advanced solid malignancies and hematological malignancies
      (including lymphomas) and for whom no standard of care treatments exist. Although treatment
      efficacy is not a primary objective of this study given its early phase nature, the patients
      screened for this study have no curative options and this study offers the potential of some
      benefit.

      The study will also characterize the PK of durvalumab and durvalumab in combination with
      tremelimumab in children and adolescents and explore potential biological activity and
      immunogenicity by assessing pharmacodynamics, anti drug antibody (ADA) levels, and anti-tumor
      activity. The results from this trial will form the basis for decisions for potential future
      pediatric studies.
    

Trial Arms

NameTypeDescriptionInterventions
Durvalumab / Tremelimumab Combination TherapyExperimentalPart 1 (dose finding) Durvalumab + tremelimumab Combination Treatment. Durvalumab and tremelimumab are initially administered at dose level 1 and dose escalated based on results from PK modeling and tolerance to determine the RP2D. Both drugs are administered every 4 weeks as intravenous infusions. Tremelimumab is only administered with durvavalumab for 4 doses, from cycles 2-5. (sarcoma, NB and NHL) Part 2 (dose expansion phase) Durvalumab + tremelimumab Combination Treatment. Durvalumab and tremelimumab are administered at the RP2D, every 4 weeks as intravenous infusions. Tremelimumab is only administered with durvalumab for 4 doses, from cycles 2-5. (solid tumors, hematological malignancies and HL) * Patients in the Hodgkin lymphoma cohort will receive durvalumab as monotherapy, administered every 4 weeks as an intravenous infusion. Tremelimumab may be added for 4 doses at time of progression.
  • Durvalumab / Tremelimumab Combination Therapy

Eligibility Criteria

        Inclusion Criteria:

          -  Max Age =17 years

          -  Solid Tumors (except primary central nervous system malignant tumors): Patients must
             have a histopathologic confirmation of malignancy. Patients must have progressed or
             are refractory to standard therapies, and for whom no standard of care treatments
             exist

          -  Malignant neoplasms of hematopoietic and lymphoid tissue and myelodysplastic syndrome:
             pathologically confirmed relapsed or refractory advanced hematological malignancies
             including lymphoma and acute leukemia

          -  Provision of diagnostic tumor sample mandated if available

          -  Evaluable disease

          -  No prior exposure to immune-mediated therapy

          -  Adequate organ and marrow function

          -  Life expectancy of at least 3 months

        Exclusion Criteria:

          -  History of allogeneic organ transplantation (exceptions may be allowed for HL, NHL,
             ALL and AML, after discussion with Sponsor). History of autologous bone marrow
             transplant may be allowed (after discussion with Sponsor).

          -  Active or prior documented autoimmune or inflammatory disorders (exceptions)

          -  Uncontrolled intercurrent illness

          -  History of primary immunodeficiency

          -  Active infection including tuberculosis, hepatitis B, C or HIV

          -  Any unresolved toxicity NCI CTCAE version 5.0 Grade ≥2 from previous anticancer
             therapy (exceptions)
      
Maximum Eligible Age:18 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Finding phase: Recommended Phase 2 Dose
Time Frame:15 months
Safety Issue:
Description:Endpoints include adult equivalent dose for both durvalumab (administered as monotherapy and in combination) and for tremelimumab, to reflect the RP2D regimen dose for durvalumab monotherapy and for the combination treatment

Secondary Outcome Measures

Measure:Pharmacokinetics (PK) of Durvalumab and Tremelimumab
Time Frame:15 months.
Safety Issue:
Description:Serum concentrations of Durvalumab and Tremelimumab

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Pediatric, solid tumors, hematological malignancies, durvalumab, tremelimumab, immunotherapy

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