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

• ClinicalTrials.gov Identifier: NCT04803123
• Recruitment Status: Recruiting
• First Posted: March 17, 2021
• Last Update Posted: July 1, 2022
• Sponsor: Dorothy Sipkins, MD, PhD
• Collaborator: Bayer
• Information provided by (Responsible Party): Dorothy Sipkins, MD, PhD, Duke University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Leukemia, Acute Lymphocytic	Drug: Copanlisib	Early Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Window Trial to Evaluate Molecular Response to PI3K Inhibition With Copanlisib in Relapsed or Refractory Adult B-cell Acute Lymphoblastic Leukemia
• Actual Study Start Date: June 21, 2021
• Estimated Primary Completion Date: May 2024
• Estimated Study Completion Date: May 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Copanilisib	Drug: Copanlisib; Patients must receive at least one dose of copanlisib prior to standard therapy to be evaluable.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. 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 ]
2. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Dorothy Sipkins, MD; 919-613-5010; dorothy.sipkins@duke.edu

Contact: Prioty Islam; 919 684 8111; prioty.islam@duke.edu

Locations

United States, North Carolina

Duke Cancer Center; Recruiting

Durham, North Carolina, United States, 27710

Contact: Dorothy Sipkins, MD 919-613-5010 dorothy.sipkins@duke.edu

Sponsors and Collaborators

Dorothy Sipkins, MD, PhD

Bayer

Investigators

• Principal Investigator: Dorothy Sipkins, MD; Duke University

More Information

• Responsible Party: Dorothy Sipkins, MD, PhD, Associate Professor of Medicine, Duke University
• ClinicalTrials.gov Identifier: NCT04803123
• Other Study ID Numbers: Pro00105967
• First Posted: March 17, 2021
• Last Update Posted: July 1, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasms by Histologic Type; Neoplasms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases