Clinical Trials /

Window Trial to Evaluate Molecular Response to PI3K Inhibition With Copanlisib in r/r Adult B-cell ALL

NCT04803123

Description:

This study will provide an evaluation of biologic markers of leukemia cell response following a single dose of copanlisib prior to any salvage induction therapy in a projected cohort of 10 relapsed/refractory B-ALL patients.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Window Trial to Evaluate Molecular Response to PI3K Inhibition With Copanlisib in r/r Adult B-cell ALL
  • Official Title: Window Trial to Evaluate Molecular Response to PI3K Inhibition With Copanlisib in Relapsed or Refractory Adult B-cell Acute Lymphoblastic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: Pro00105967
  • NCT ID: NCT04803123

Conditions

  • Leukemia, Acute Lymphocytic

Interventions

DrugSynonymsArms
CopanlisibCopanilisib

Purpose

This study will provide an evaluation of biologic markers of leukemia cell response following a single dose of copanlisib prior to any salvage induction therapy in a projected cohort of 10 relapsed/refractory B-ALL patients.

Trial Arms

NameTypeDescriptionInterventions
CopanilisibExperimental
  • Copanlisib

Eligibility Criteria

        Inclusion Criteria:

          1. Relapsed/refractory, Philadelphia chromosome positive or negative, B-cell, adult (≥
             age 18) acute lymphoblastic leukemia (including bone marrow, extramedullary, CNS
             disease, or all), with or without prior hematopoietic stem cell transplant.

             Philadelphia chromosome positive patients prior to enrollment must have documented
             treatment failure to all FDA-approved for use in R/R ALL tyrosine kinase inhibitor
             (TKI) therapy, or have previously been deemed by their treating physician to not be a
             candidate for further TKI therapy.

          2. ECOG 0-3.

          3. CrCl ≥ 30 mL/minute.

          4. Bilirubin ≤ 1.5x upper limit of normal (ULN), AST/ALT ≤ 3x ULN.

          5. Any patients with known pulmonary disease (including COPD, asthma, ongoing tobacco
             use, pulmonary hypertension, pulmonary sarcoidosis, or other relevant pulmonary
             disease which severely limits their pulmonary function), require an assessment of lung
             capacity with pulmonary function testing prior to acceptance to the study, with a
             threshold acceptance of DLCO > 40% corrected.

        Exclusion Criteria:

          1. History of or concurrent condition of interstitial lung disease or autoimmune
             pneumonitis.

          2. Active pneumonia requiring treatment, including Pneumocystis jirovecci pneumonia
             (PJP).

          3. History of type 1 diabetes mellitus.

          4. Type 2 diabetes mellitus with HgbA1C ≥10% while on treatment for diabetes.

          5. Uncontrolled hypertension despite optimal medical management (per investigator's
             assessment).

          6. Untreated human immunodeficiency virus (HIV).

          7. Active replication of hepatitis B or active hepatitis C. Those with prior disease who
             are PCR negative at enrollment and meet liver function eligibility criterion are
             eligible.

          8. Cytomegalovirus (CMV) infection with positive PCR at baseline. CMV PCR test is
             considered positive if the result can be interpreted as a CMV viremia according to
             institutional standard.

          9. History of hematopoietic stem cell transplant with active GVHD requiring > 10 mg of
             prednisone daily or equivalent.

         10. History of calcineurin inhibitor use in the last 28 days prior to enrollment.

         11. Patients requiring immediate cytoreductive therapy. Exceptions for: patients whose
             peripheral blast counts are being controlled by single agent or combination therapy
             with steroids and/or hydroxyurea.

         12. Pregnancy.

         13. Active concurrent malignancy requiring ongoing treatment. Exceptions for: resected
             breast cancer being treated with hormonal therapy only, prostate cancer treated with
             hormonal therapy not progressing within the past year, if subject has received
             definitive local therapy (i.e., surgical excision, external beam radiation, or other
             local therapy with curative intent), non-melanoma skin cancers, or carcinoma in situ.

         14. Active COVID-19 infection.

         15. Progressive and/or uncontrolled infections despite active treatment.

         16. Patients with residual toxicities related to prior treatment (including chemotherapy,
             immunotherapy, clinical trial, surgery, radiotherapy, or hematopoietic stem cell
             transplant) persistently > Grade 1 despite adequate treatment. Exceptions for:
             patients with residual toxicity related to prior treatment of ≤Grade 2 which is stable
             prior to enrollment and for which the natural history would not be expected to change
             over time; toxicity which cannot be reasonably excluded to be due to disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Evaluate the effect of copanlisib exposure on alpha-6 integrin expression levels in leukemic blasts using flow cytometry.
Time Frame:1 year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Evaluate the effect of copanlisib exposure on proliferation of ALL blasts as determined by flow cytometric blast cell Ki-67 index.
Time Frame:1 year
Safety Issue:
Description:
Measure:Evaluate the effect of copanlisib exposure on proliferation of ALL blasts as determined by peripheral blood hematologic parameters (CBC and WBC differential including blast percentage).
Time Frame:1 year
Safety Issue:
Description:

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dorothy Sipkins, MD, PhD

Last Updated

July 21, 2021