Rituximab, Acalabrutinib, and Durvalumab (RAD) in Primary CNS Lymphoma.

NCT04688151 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: T2420
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability and determine the recommended phase 2/phase 3 dose of RAD regimen in PCNSL

Conditions

Primary Central Nervous System Lymphoma (PCNSL)

Outcome Measures

Primary Outcomes (1)

• MTD of acalabrutinib

  Dose-limiting toxicity (DLT) patients will be enrolled in cohort of 2 to receive escalating dose of acalabrutinib at two dose levels (level I 100mg PO once , level II 100mg PO twice every day) or more of defined events

  From date of registration until the date of definition of MTD of first documented progression or date of death from any cause, whichever came first, assessed up to 28 weeks.

Secondary Outcomes (1)

• Tumor response

  From date of registration until the date of definition of MTD of first documented progression or date of death from any cause, whichever came first, assessed up to 28 weeks.

Study Arms (1)

Dose level 1,Dose level 2

EXPERIMENTAL

Dose level 1 Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO once every day Durvalumab 1500mg infusion once every 4 weeks Dose level 2 Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO twice every day Durvalumab 1500mg infusion once every 4 weeks

Drug: Rituximab

Interventions

Rituximab DRUG

Dose level 1:Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO once every day Durvalumab 1500mg infusion once every 4 weeks Dose level 2:Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO twice every day Durvalumab 1500mg infusion once every 4 weeks Expansion:Determined by the result of the dose escalation phase

Also known as: Acalabrutinib, Durvalumab

Dose level 1,Dose level 2

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male, 20 years of age or older.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3.
• Histologically or cytologically proven diagnosis of primary CNS lymphomas of large B-cell type in one of the following clinical status:
• Fail to achieve optimal response (CR or PR) after at least one prior therapy with all the toxicities recovered to grade 1 or less from the prior therapy.
• Has confirmed disease relapse or disease progression after at least one prior therapy with all the toxicities recovery to grade 1 or less from the prior therapy.
• Intolerable to the prior therapy because of toxicities with all the toxicities recovery to grade 1 or less from the prior therapy.
• Treatment naïve but unable or not willing to receive high-dose methotrexate-based induction chemotherapy.
• Have at least one measurable brain parenchymal lesion that can be measured by brain MR or CT images.
• Have adequate organ functions as defined by the following criteria:
• Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≦3 x upper limit of normal (ULN).
• Total serum bilirubin ≦2 x ULN (except for Gilbert's syndrome)
• Absolute neutrophil count (ANC) ≧1,000/mL; Platelets ≧50,000/mL; Hemoglobin≧8.0 g/dL.
• Serum creatinine ≦2.0 x ULN.
• Prothrombin time/International normalized ratio (PT/INR) ≦2.0 x ULN and partial thromboplastin time (PTT) ≦2.0 x ULN.
• Any major surgery must have been completed at least 4 weeks prior to study entry. Any prior therapies, including chemotherapy, rituximab, or high dose or high potency corticosteroids intended to treat lymphoma (dose higher than 100 mg hydrocortisone per day or equivalent potency), must have been completed at least 2 weeks prior to the study entry. However, low-dose, low-potency steroids (ie, up to 100 mg hydrocortisone per day or equivalent potency) may be used prior to the initiation of the trial therapy for the relief of lymphoma-related symptoms. Non-regular steroid administration for premedication purpose are allowed (refer to section 7.7). Any prior radiation performed with curative (i.e., not only palliative) intent or minor surgeries/procedures must have been completed at least 2 weeks prior to the initiation of study medication. Palliative radiation (≤10 fractions) must have been completed 48 hours prior the start of the trial therapy commencing. Any acute toxicity must have been recovered to grade 1 (except alopecia).

You may not qualify if:

• Diagnosis with secondary CNS lymphoma, i.e. systemic lymphoma with CNS involvement or relapse, or diagnosis with PCNSL but with other non-CNS, systemic involvement.
• Active or uncontrolled autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia.
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
• Patients with any chronic skin condition that does not require systemic therapy.
• Patients with other autoimmune or inflammatory disorders that are not active in the last 2 years may be included.
• Patients with celiac disease controlled by diet alone.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of the trial therapy and of low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease.
• Has positive HBV surface antigen (HBsAg) result. Patients who are negative for HBsAg but are positive for anti-HBc antibody are allowed to be enrolled if their HBV-DNA test are negative.
• Has positive HCV-RNA result.
• Has positive anti-human immunodeficiency virus (HIV)-1/2 antibody test results.
• Prior history of anaphylaxis or severe allergic reactions to anyone of the study drugs or the excipients.

Sponsors & Collaborators

• National Health Research Institutes, Taiwan: lead
• National Taiwan University Hospital: collaborator
• National Cheng-Kung University Hospital: collaborator
• China Medical University Hospital: collaborator
• Chang Gung Memorial Hospital: collaborator

Study Sites (1)

Shang-Ju Wu

Taipei, Taiwan

Location

MeSH Terms

Interventions

Rituximab; acalabrutinib; durvalumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Shang-Ju Wu, M.D

  National Taiwan University Hospital, Taipei, Taiwan

  PRINCIPAL INVESTIGATOR

• Su-Peng Yeh, M.D

  China Medical University Hospital

  PRINCIPAL INVESTIGATOR

• Kwang-Yu Chang, M.D

  National Cheng Kung University Hospital,Taiwan

  PRINCIPAL INVESTIGATOR

• Ming Chung Wang, M.D

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: This study will use the 3+3 design in the dose escalation phase.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Dose level 1,Dose level 2,3+3 design in the dose escalation.

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 29, 2020
• Study Start: February 22, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: May 22, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)