RECRUITING

Acalabrutinib With DA-EPOCH-R or R-CHOP for People With Untreated Diffuse Large B-cell Lymphoma

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Conditions

Non-Hodgkin's LymphomaDiffuse Large B-Cell LymphomaDLBCLNHLBTK InhibitorCalquenceACP-196Monoclonal Antibody

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Background: Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. Most people with this cancer can be cured. But those who are not cured have a poor prognosis. Researchers want to add another drug to standard treatment see if it can improve the cure rate. Objective: To see if the drug acalabrutinib given with rituximab and standard combination chemotherapy can improve the cure rate of aggressive B-cell lymphomas such as diffuse large B-cell lymphoma. Eligibility: People ages 18 and older with an aggressive B-cell lymphomas that have not been treated Design: Participants will be screened with: Blood and urine tests Physical exam Medical history Tumor biopsy Bone marrow biopsy: A needle will remove marrow from the participant s hipbone. Lumbar puncture: If necessary, a needle will remove fluid from the participant s spinal canal. Imaging scans Participants will take the study drug for up to 14 days. It is a pill taken 2 times a day. Then they will have more scans. They will get rituximab and chemotherapy. They may get these drugs through a needle in an arm vein. Or they may them through a tube placed in a vein in their chest or in their neck. They might also keep taking the study drug. Each treatment cycle lasts 21 days. They will have up to 6 cycles. Participants may have 4 doses of another drug injected into their spinal fluid. Participants will have repeats of the screening tests throughout the study. Participants will have a follow-up visit 30 days after their last treatment, then every 3 months for 2 years, then every 6 months for 3 years, and then yearly.

Official Title

A Phase 2 Study of Acalabrutinib With DA-EPOCH-R or R-CHOP for Patients With Untreated Diffuse Large B-cell Lymphoma

Quick Facts

Study Start:2019-08-05
Study Completion:2030-03-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04002947

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. 1. Patients must have a confirmed histologic diagnosis of an aggressive B-cell lymphoma with morphologic appearance of DLBCL or high-grade B-cell lymphoma (HGBL) confirmed by the Laboratory of Pathology, NCI, with no prior treatment for DLBCL or HGBL. The following subtypes are included:
  2. * DLBCL, NOS, Activated B-cell type (ABC)
  3. * DLBCL, NOS, Germinal center B-cell type (GCB)
  4. * T-cell/histiocyte-rich large B-cell lymphoma
  5. * Primary cutaneous DLBCL, leg-type
  6. * EBV+ DLBCL, NOS
  7. * DLBCL associated with chronic inflammation
  8. * ALK+ large B-cell lymphoma
  9. * High-grade B-cell lymphoma, NOS
  10. * High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
  11. 2. A formalin-fixed tissue block or 15 slide of tumor sample (archival or fresh) must be available for performance of correlative studies.
  12. 3. Measurable lymph nodes or masses of at least 1.5 centimeters (cm) on baseline CT or MRI
  13. 4. Stage II, III, or IV disease as classified by the Ann Arbor Classification
  14. 5. Age greater than or equal to 18 years
  15. 6. ECOG performance status less than or equal to 2.
  16. 7. Adequate organ and marrow function as defined below unless dysfunction is felt to be secondary to lymphoma involvement as determined by the treating investigator:
  17. * absolute neutrophil count\* \>=1,000/mcL
  18. * hemoglobin\* \>= 8 g/dL (transfusions permitted to meet criteria)
  19. * Platelets \>= 75,000/mcL (transfusions not permitted)
  20. * total bilirubin \<= 1.5 X institutional ULN (or \<= 3 X institutional ULN for patients with documented Gilberts syndrome or cholestatic obstruction or involvement by lymphoma)
  21. * AST(SGOT)/ALT(SGPT) \<= 3 X institutional ULN (\<= 5 x ULN for patients with cholestatic obstruction or involvement by lymphoma
  22. * Serum creatinine \<= 2.0 mg/dL
  23. 8. Effects of acalabrutinib on the developing human fetus are unknown. For these reasons the following measures apply:
  24. * Individuals of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment.
  25. * Individuals of childbearing potential who are sexually active must agree to highly effective contraception prior to study entry, for the duration of study participation, and for at least 2 days after the last dose of acalabrutinib or 12 months after the last dose of combined chemotherapy, whichever is later. Individuals who can father children must use highly effective contraception prior to study entry, for the duration of study participation, and for 12 months after the last dose of combined chemotherapy; there is no contraception timing requirement post-last dose of acalabrutinib alone if an individual who can father children does not initiate chemotherapy on study after the acalabrutinib window.
  26. * Participants must not be planning to conceive or father children within the projected duration of the trial, starting with the pre-screening/screening visit through 2 days after the last dose of acalabrutinib or 12 months after the last dose of combined chemotherapy, whichever is later.
  27. * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, which may be oral, intravaginal, or transdermal
  28. * Progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable
  29. * Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
  30. * Bilateral tubal occlusion
  31. * Vasectomy of participant or participant's partner (with medical assessment and confirmation of vasectomy surgical success)
  32. * Sexual abstinence (only if refraining from heterosexual intercourse during the entire period of risk associated with the study treatments)
  33. 9. Ability of patient to understand and the willingness to sign a written informed consent document.
  34. 10. Any HIV status will be included in this study; status must be confirmed prior to enrollment.
  1. 1. Patients who meet histologic criteria for the following subtypes are excluded:
  2. * Primary DLBCL of the central nervous system (PCNSL)
  3. * Primary mediastinal B-cell lymphoma (PMBL)
  4. * Plasmablastic lymphoma
  5. * Intravascular large B-cell lymphoma
  6. * B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
  7. 2. Patients who, at the discretion of the investigator, need immediate cytoreductive chemotherapy such as patients with evidence of spontaneous tumor lysis or impending organ compromise are not eligible.
  8. 3. Current or prior anti-cancer treatment for DLBCL prior to enrollment. Short course of corticosteroids (\<7 days) for acute issues prior to study enrollment are permitted.
  9. 4. Major surgical procedure within 30 days of first dose of study drug. If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
  10. 5. Requires treatment with moderate or strong CYP3A inhibitors or inducers
  11. 6. Known lymphomatous involvement of the CNS
  12. 7. Pregnant individuals, or individuals who intend to become pregnant during the study are excluded from this study because of potential teratogenic effects associated with acalabrutinib, R-CHOP, and/or DA-EPOCH-R
  13. 8. The potential for all study treatments to be excreted in the milk of nursing mothers is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with acalabrutinib, nursing must be discontinued.
  14. 9. Uncontrolled intercurrent illness including, but not limited to the following that may limit interpretation of results or that could increase risk to the patient at the discretion of the investigator:
  15. * Any condition that requires anticoagulation with warfarin or equivalent vitamin K antagonist
  16. * Active bleeding, history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
  17. * Suspected or confirmed Progressive Multifocal Leukoencephalopathy (PML)
  18. * Active hepatitis C infection. NOTE: Subjects who are hepatitis C antibody positive will need to have a negative HCV PCR result before enrollment. Those with a positive PCR for hepatitis C are excluded.
  19. * Active hepatitis B infection. NOTE: Patients who are hepatitis B surface antigen (HbsAg) positive will be excluded from enrollment. Patients who are hepatitis B core antibody (HbcAb) positive will need to have a negative HBV PCR result before enrollment. Those with a positive PCR for hepatitis B are excluded. Those who are hepatitis B core antibody (HbcAb) positive with a negative PCR for hepatitis B will be treated with antivirals designed to prevent hepatitis B reactivation (e.g., entecavir) throughout therapy and for 12 months after therapy and have monitoring for hepatitis B reactivation with PCR.
  20. * History of hemorrhagic stroke or intracranial hemorrhage in preceding 6 months
  21. * Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification. Subjects with controlled atrial fibrillation/flutter during screening are eligible.
  22. * Uncontrolled autoimmune hemolytic anemia
  23. * Inability to swallow oral medications, or disease involve that significantly limits absorption of oral medication
  24. * Known mental or physical illness that would interfere with cooperation with the requirements of the trial or confound the results or interpretation of the results of the trial and, in the opinion of the treating investigator, would make the patient inappropriate for entry into the study.
  25. 10. Concurrent participation in another therapeutic clinical trial.

Contacts and Locations

Study Contact

NCI Medical Oncology Referral Office
CONTACT
(240) 760-6050
ncimo_referrals@nih.gov
Christopher J Melani, M.D.
CONTACT
(240) 760-6057
christopher.melani@nih.gov

Principal Investigator

Christopher J Melani, M.D.
PRINCIPAL_INVESTIGATOR
National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

  • Christopher J Melani, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-08-05
Study Completion Date2030-03-31

Study Record Updates

Study Start Date2019-08-05
Study Completion Date2030-03-31

Terms related to this study

Keywords Provided by Researchers

  • BTK Inhibitor
  • Calquence
  • ACP-196
  • Monoclonal Antibody

Additional Relevant MeSH Terms

  • Non-Hodgkin's Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • DLBCL
  • NHL