Acalabrutinib Plus RICE for Relapsed/Refractory DLBCL

NCT03736616 | Unknown Phase 2 FDA Drug

• 1 other identifier: ESR-LY-808-SCI
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the tolerability,feasibility, and efficacy of combining acalabrutinib with RICE chemotherapy as second line therapy in relapsed/refractory DLBCL patients with separate primary objectives in each of in two cohorts: Cohort A: Hematopoeitic stem cell transplantation (HSCT) eligible patients undergoing second-line salvage chemoimmunotherapy \[Rituximab, Ifosfamide, Carboplatin, and Etoposide (RICE)\] plus acalabrutinib:. Cohort B: Individuals not eligible for HSCT undergoing second-line salvage chemoimmunotherapy \[Rituximab, Ifosfamide, Carboplatin, and Etoposide (RICE)\] plus acalabrutinib followed by acalabrutinib as a maintenance therapy

Conditions

Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Cohort A: Complete Response Rate

  To estimate the confirmed complete response (CR) rate (RECIL 2017 criteria) prior to transplant in patients undergoing second-line therapy for relapsed/refractory DLBCL.

  10 weeks

• Cohort B: Progression Free Survival

  To estimate the one-year progression free survival rate in patients undergoing second-line induction and maintenance therapy for relapsed/refractory DLBCL.

  1 year

Secondary Outcomes (2)

• Cohort A: Treatment Response

  10 weeks

• Cohort B: Treatment Completion

  17 weeks

Other Outcomes (3)

• Cohorts A and B: Overall Response Rate

  1 year

• Cohorts A and B: Incidence of treatment-related Grade 3 and 4 Adverse events as assessed by CTCAE v4.0

  1.5 years

• Cohorts A and B: Incidence of Serious Adverse Events

  1.5 years

Study Arms (2)

Cohort A: Transplant eligible

EXPERIMENTAL

Patients receive RICE: Rituximab 375mg/m2 IV d1, Ifosfamide 5000mg/m2, Carboplatin area under curve (AUC) 5 IV d2, Etoposide (VP16) 100mg/m2 IV d1-3 \& Acalabrutinib 100mg oral BID d1-21. Cycle is 21 days for up to 3 cycles of treatment. BEAM chemotherapy \& autoHSCT: BEAM given as Carmustine (BCNU) 300mg/m2 IV day -6 respective to stem cell infusion, VP16 200mg/m2 IV BID day -5 to day-2, Cytarabine (Ara-C) 200mg/m2 IV BID day -5 to day -2, and Melphalan 140mg/m2 IV day -1. Autologous hematopoietic stem cell infusion on day 0. Only patients with CR/PR after RICE acalabrutinib will undergo BEAM and autoHSCT Maintenance therapy: Post autoHSCT patients will receive Acalabrutinib 100mg oral BID starting on day +30 for 12 consecutive months or until progression or intolerance if occurs within those 12 months.

Drug: Carboplatin; Drug: Ifosfamide; Drug: Etoposide; Biological: Rituximab; Drug: Carmustine; Drug: Cytarabine; Drug: Melphalan; Other: Autologous HSCT; Drug: Acalabrutinib

Cohort B: Transplant ineligible

EXPERIMENTAL

Patients receive RICE chemoimmunotherapy + Acalabrutinib Salvage therapy: RICE: Rituximab 375mg/m2 IV d1, Ifosfamide 5000mg/m2, Carboplatin AUC 5 IV d2, Etoposide 100mg/m2 IV d1-3. Acalabrutinib 100mg oral BID d1-21. Cycle is 21 days for up to 3 cycles of treatment. Maintenance therapy: Patients will receive Acalabrutinib 100mg oral BID for 12 consecutive months or until progression or intolerance if occurs within those 12 months. Maintenance therapy will only be given to patients with stable disease or better response after 3 cycles of RICE+ acalabrutinib

Drug: Carboplatin; Drug: Ifosfamide; Drug: Etoposide; Biological: Rituximab; Drug: Acalabrutinib

Interventions

Carboplatin DRUG

Chemotherapy

Cohort A: Transplant eligible; Cohort B: Transplant ineligible

Ifosfamide DRUG

Chemotherapy

Cohort A: Transplant eligible; Cohort B: Transplant ineligible

Etoposide DRUG

Chemotherapy

Also known as: VP-16

Cohort A: Transplant eligible; Cohort B: Transplant ineligible

Rituximab BIOLOGICAL

Anti-CD20 mAb

Also known as: Rituxan

Cohort A: Transplant eligible; Cohort B: Transplant ineligible

Carmustine DRUG

Chemotherapy

Also known as: BCNU

Cohort A: Transplant eligible

Cytarabine DRUG

Chemotherapy

Also known as: ARA-C

Cohort A: Transplant eligible

Melphalan DRUG

Chemotherapy

Cohort A: Transplant eligible

Autologous HSCT OTHER

Cellular Therapy

Also known as: Autologous Hematopoeitic Stem Cell Transplantation

Cohort A: Transplant eligible

Acalabrutinib DRUG

Bruton's Tyrosine Kinase Inhibitor

Cohort A: Transplant eligible; Cohort B: Transplant ineligible

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed R/R DLBCL (per 2008 WHO classification)
• GCB or ABC cell of origin (by IHC using Hans algorithim)
• Transformation from prior indolent NHL is permitted
• Relapsed or refractory to 1 prior line of anthracycline containing chemoimmunotherapy considered a standard 1st line therapy for DLBCL. Acceptable 1st line regimens are R-CHOP, R-EPOCH, or R-HyperCVAD chemotherapy regimens. Treatment with prior radiotherapy is allowed.
• ECOG Performance status 0-2
• Expected life expectancy of at least 3 months
• Age 18 years or older
• Disease measurable by FDG-PET that meets iWNHL size criteria (\>1.5cm in longest diameter for lymph node or nodal mass, or \>1.0cm in longest diameter for extranodal disease)
• For Cohort A, patients must meet institutional eligibility guidelines for autologous HCT and all of the following
• Ejection fraction \>40% by ECHO or MUGA
• Pulmonary function testing with corrected DLCO \>50% of predicted
• Charlson Comorbidity Index \<6
• For Cohort B, patients must be considered medically ineligible for autologous HCT by fulfilling one or more of following.
• Age \>75
• Any chronic medical condition, treated or untreated, for which the anticipated risks of autologous HCT are deemed by the investigator to outweigh potential benefit of autologous HCT.

You may not qualify if:

• Inadequate organ function, including the following
• Hematologic: ANC \<1000/uL, PLT \<50,000/uL, and hemoglobin \<7.0g/dL. If the patient is known to have bone marrow involvement with cytopenias directly attributed to disease, eligibility may be permitted per investigator's discretion.
• Hepatic: Total bilirubin ≥ 2.0 x ULN unless bilirubin elevation is due to Gilbert's syndrome or of non-hepatic origin. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 3 x upper limit of normal (ULN)
• Renal: Estimated creatinine clearance of \< 29 mL/min, calculated using the formula of Cockcroft and Gault \[(140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female\].
• GI: Malabsorption syndrome or gastrointestinal disease that limits oral absorption of medication
• Prior history of autologous or allogeneic HCT
• Any known contraindication to ifosfamide, etoposide, carboplatin, or rituximab
• Active chronic hepatitis B infection, defined by positive Hep B DNA PCR.
• Active chronic hepatitis C infection, defined by positive Hep C RNA PCR
• Requires treatment with a strong CYP3A inhibitor/inducer
• Any history of known significant bleeding diathesis
• History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug.
• Pregnant or breastfeeding
• Any uncontrolled active fungal, bacterial, or viral systemic infection that is untreated or not responsive to antimicrobial therapy.
• Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk.

Sponsors & Collaborators

• Swedish Medical Center: lead
• Acerta Pharma BV: collaborator

Study Sites (1)

Swedish Cancer Institute

Seattle, Washington, 98104, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Carboplatin; Ifosfamide; Etoposide; Rituximab; Carmustine; Cytarabine; Melphalan; acalabrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Study Officials

• Krish Patel, MD

  Swedish Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Neil Bailey

CONTACT

206-215-1471; Neil.Bailey@swedish.org

Swedish Research

CONTACT

206-215-3086; cancerresearch@swedish.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2018
• First Posted: November 9, 2018
• Study Start: August 16, 2019
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: July 22, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)