Relapsed Diffuse Large B-Cell LymphomaPhase 1NCT03136497
A Study of ABT-199 Plus Ibrutinib and Rituximab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
A Phase 1 study testing 400mg ABT-199, Ibrutinib and Rituximab in people with Relapsed Diffuse Large B-Cell Lymphoma and Refractory Diffuse Large B-Cell Lymphoma, run by Hackensack Meridian Health at 1 site in United States.
Trial summary
A Study of Venetoclax Plus Ibrutinib and Rituximab in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL). Our hypothesis is that the combination therapy of BTK (Bruton's tyrosine kinase) Inhibitor Ibrutinib plus Venetoclax and Rituximab in relapsed or refractory DLBCL will have an increased… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma
- What is being tested?
- 400mg ABT-199, Ibrutinib and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Sep 2017to 9 Nov 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ECOG (Eastern Cooperative Oncology Group) Performance Status </= 2.
- Histologically or cytologically confirmed diagnosis of advanced DLBCL.
- Ability and willingness to comply with the requirements of the study protocol
- Prior therapy: relapsed or refractory patients who have received one prior therapy are eligible. If treated with small molecule, washout therapy with a period of greater than 5 times the half-life of the molecule. Patients who have previously received high-dose chemotherapy with peripheral stem cell support are eligible. Washout period of 21 days.
- Presence of at least one lymph node evaluable or mass measurable for response.
- Age greater than or equal to 18 years.
Show all 16Show fewer
- Recovery from any previous treatment therapy.
- Laboratory parameters:
- Absolute neutrophil count (ANC) 1000/mm3 independent of growth factor support (unless the treating physician deems the neutropenia is related to bone marrow involvement, then an ANC of > 750/mm3 is allowed)
- Platelets 100,000/mm3 or 50,000/mm3 if bone marrow involvement independent of transfusion support in either situation
- Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
- Aspartate Aminotransferase (AST, SGOT) and Alanine Aminotransferase (ALT, SGPT) ≤ 3 x upper limit of normal (ULN)
- Creatinine: Creatinine Clearance (CrCl) 50 ml/min (calculated using Cockcroft-Gault Formula-Appendix 2) -Prothrombin time (PT)or international normalized ratio and partial thromboplastin time (PTT) not to exceed 1.2 times the institution's normal range
- Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 3 months after Venetoclax and 12 months after Rituximab For males, these restrictions apply for 3 months after the last dose of study drug.
- Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [-hCG]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study.
- Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
Who cannot join
- Known central nervous system lymphoma.
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon).
- Received the following agents within 7 days prior to the first dose of venetoclax or requires chronic treatment with strong Cytochrome P450 3A4 (CYP3A) inhibitors (e.g., ketoconazole, ritonavir, clarithromycin, itraconazole, voriconazole), moderate CYP3A inhibitors (e.g., erythromycin, ciprofloxacin, diltiazem, fluconazole, verapamil), strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine). (See Appendix 4)
- 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.
- Vaccinated with live, attenuated vaccines within 4 weeks of randomization.
Show all 27Show fewer
- Use of any other standard chemotherapy, radiation therapy, or experimental drug therapy for the treatment of DLBCL within 21 days of starting treatment
- Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection or human T-cell leukemia virus 1 (HTLV-1) seropositive status
- 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 ibrutinib capsules, venetoclax or rituximab or put the study outcomes at undue risk.
- History of uncontrolled or symptomatic angina
- Ejection fraction below the institutional normal limit
- History of other malignancy that could affect compliance with the protocol or interpretation of results
- Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are generally eligible. Patients with a malignancy that has been treated, but not with curative intent, will also be excluded, unless the malignancy has been in remission without treatment for 2 years prior to enrollment.
- Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal)
- Major surgery (within 4 weeks prior to the start of the first dose of study treatment), other than for diagnosis
- Women who are pregnant or lactating
- Female patients who are not surgically sterile or postmenopausal (for at least 1 year) must practice at least one of the following methods of birth control throughout the duration of study participation and for at least 12 months after study treatment:
- Total abstinence from sexual intercourse
- A vasectomized partner
- Hormonal contraceptives (oral, parenteral, vaginal ring, or transdermal) that started at least 3 months prior to study drug administration
- Double-barrier method (condom diaphragm or cervical cup with spermicidal contraceptive sponge, jellies, or cream)
- Non-vasectomized male patients must comply with at least one of the following methods of birth control throughout the duration of study participation and for at least 12 months after study treatment:
- A partner who is surgically sterile or postmenopausal (for at least 1 year) or who is taking hormonal contraceptives (oral, parenteral, vaginal ring, or transdermal) for at least 3 months prior to study drug administration
- Total abstinence from sexual intercourse
- Double-barrier method (condom diaphragm or cervical cup with spermicidal, contraceptive sponge, jellies, or cream)
- Malabsorption syndrome or other condition that precludes enteral route of administration
- Known allergy to both xanthine oxidase inhibitors and rasburicase
Trial locations and contacts
1 site in 1 country.
United States1 site
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
About this study
Official title: Phase Ib Dose Finding Study of ABT-199 (A-1195425.0) Plus Ibrutinib (PCI-32765) and Rituximab in Patients With Relapsed/Refractory Diffuse Large B-cell NHL (DLBCL)
A Study of Venetoclax Plus Ibrutinib and Rituximab in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL).
Our hypothesis is that the combination therapy of BTK (Bruton's tyrosine kinase) Inhibitor Ibrutinib plus Venetoclax and Rituximab in relapsed or refractory DLBCL will have an increased activity with acceptable toxicity. Furthermore, this new novel therapeutic combination will be safe and well tolerated among this patient population.
Read the detailed description
This is a Phase 1b, single-arm, open-label, single-center study of venetoclax (ABT-199) in combination with ibrutinib and rituximab in Subjects with Relapsed/Refractory DLBCL. The trial consists of a dose-escalation of venetoclax in combination with standard doses of ibrutinib and rituximab. For the dose escalation part of the study, a standard 3+3 design will be utilized. Once the MTD has been established, the dose escalation part will be followed by a dose expansion part in a cohort with a maximum of 24 subjects with DLBCL. The purpose of the dose expansion part is to investigate the efficacy of the combination. Between the dose-escalation and dose-expansion, the maximum number of subjects will be 30.
Cycle length will be 28 days. Venetoclax will be administered orally QD (Once Daily), continuously for 24 cycles. Ibrutinib will be administered orally QD, continuously for 24 cycles. Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1), Commercially available rituximab IV will be used.
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
400mg ABT-199Drug
Also called A-1195425.0, Venetoclax
Oral dose daily until disease progression
IbrutinibDrug
Also called PIC-32765, Imbruvica
Oral dose daily until disease progression
RituximabDrug
Also called Rituxan
Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1
800mg ABT-199Drug
Also called A-1195425.0, Venetoclax
Oral dose daily until disease progression
| Study group | Role | What they receive |
|---|---|---|
| 400mg ABT-199 | Experimental | Cycle length will be 28 days. 400mg ABT-199 will be administered orally QD (Once Daily), continuously for 24 cycles. Ibrutinib will be administered orally QD, continuously for 24 cycles. Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1), Commercially available rituximab IV will be used. Receives: Drug: 400mg ABT-199; Drug: Ibrutinib; Drug: Rituximab |
| 800mg ABT-199 | Experimental | Cycle length will be 28 days. 800mg ABT-199 will be administered orally QD (Once Daily), continuously for 24 cycles. Ibrutinib will be administered orally QD, continuously for 24 cycles. Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1), Commercially available rituximab IV will be used. Receives: Drug: Ibrutinib; Drug: Rituximab; Drug: 800mg ABT-199 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
Define maximum tolerated dose and /or recommended phase II dose for the combinations of venetoclax (ABT-199, GDC-0199) plus Ibrutinib (PCI-32765) and rituximab in Relapsed or Refractory DLBCL by assessing the incidence of dose limiting toxicities (DLTs).
Measured: 29 days
Secondary outcomes (3)
Incidence of Treatment-emergent Adverse Events.
Adverse events will be assessed using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03.
Measured: 36 Months
Efficacy as Assessed by Progression Free Survival (PFS)
The duration of PFS is defined as the time from the beginning of the first cycle of treatment to the date of progressive disease or death from any cause. PFS will be estimated using Kaplan-Meier method.
Measured: 36 Months
Efficacy as Assessed by Overall Survival (OS)
The duration of OS is defined as the time from the beginning of the first cycle of treatment to the date of death from any cause. OS will be estimated using Kaplan-Meier method.
Measured: 36 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2017
- Study start5 Sep 2017
- Primary completion9 Nov 2020
- Study completion9 Nov 2020
Why it stopped: Lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (45)Papers the sponsor has linked to this study.
- Other trials for Relapsed Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hackensack Meridian Health
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC, Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Andre Goy, MD, Principal investigator, Hackensack Meridian Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03136497
- Sponsor's protocol ID
- Pro00005671
- Other IDs
- 54179060LYM1004, ML30063
- Status last verified
- Jun 2024
- First submitted
- 20 Apr 2017
- Last updated
- 23 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Borner C. The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol. 2003 Jan;39(11):615-47. doi: 10.1016/s0161-5890(02)00252-3.
PubMed 12493639Binet JL, Auquier A, Dighiero G, Chastang C, Piguet H, Goasguen J, Vaugier G, Potron G, Colona P, Oberling F, Thomas M, Tchernia G, Jacquillat C, Boivin P, Lesty C, Duault MT, Monconduit M, Belabbes S, Gremy F. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981 Jul 1;48(1):198-206. doi: 10.1002/1097-0142(19810701)48:13.0.co;2-v.
PubMed 7237385Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol. 2004 Oct;127(1):3-11. doi: 10.1111/j.1365-2141.2004.05094.x.
PubMed 15384972Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM. MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5166-71. doi: 10.1073/pnas.0800121105. Epub 2008 Mar 24.
PubMed 18362358Catovsky D, Richards S, Matutes E, Oscier D, Dyer M, Bezares RF, Pettitt AR, Hamblin T, Milligan DW, Child JA, Hamilton MS, Dearden CE, Smith AG, Bosanquet AG, Davis Z, Brito-Babapulle V, Else M, Wade R, Hillmen P; UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group; NCRI Chronic Lymphocytic Leukaemia Working Group. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007 Jul 21;370(9583):230-239. doi: 10.1016/S0140-6736(07)61125-8.
PubMed 17658394Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S, Rai KR. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996 Jun 15;87(12):4990-7. No abstract available.
PubMed 8652811Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.
PubMed 25113753Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. doi: 10.1056/NEJMoa011795.
PubMed 11807147Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Ferme C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. doi: 10.1182/blood-2010-03-276246. Epub 2010 Jun 14.
PubMed 20548096Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002 Sep;2(9):647-56. doi: 10.1038/nrc883.
PubMed 12209154Cory S, Huang DC, Adams JM. The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene. 2003 Nov 24;22(53):8590-607. doi: 10.1038/sj.onc.1207102.
PubMed 14634621Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang Y, Xu W, Shaffer AL, Wright G, Xiao W, Powell J, Jiang JK, Thomas CJ, Rosenwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Connors JM, Johnson NA, Rimsza LM, Campo E, Jaffe ES, Wilson WH, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pierce SK, Staudt LM. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature. 2010 Jan 7;463(7277):88-92. doi: 10.1038/nature08638.
PubMed 20054396Del Gaizo Moore V, Brown JR, Certo M, Love TM, Novina CD, Letai A. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest. 2007 Jan;117(1):112-21. doi: 10.1172/JCI28281.
PubMed 17200714Del Gaizo Moore V, Letai A. Rational design of therapeutics targeting the BCL-2 family: are some cancer cells primed for death but waiting for a final push? Adv Exp Med Biol. 2008;615:159-75. doi: 10.1007/978-1-4020-6554-5_8.
PubMed 18437895Dighiero G, Binet JL. When and how to treat chronic lymphocytic leukemia. N Engl J Med. 2000 Dec 14;343(24):1799-801. doi: 10.1056/NEJM200012143432410. No abstract available.
PubMed 11114321
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Dose Finding Study of ABT-199 (A-1195425.0) Plus Ibrutinib (PCI-32765) and Rituximab in Patients With Relapsed/Refractory Diffuse Large B-cell NHL (DLBCL)
- ClinicalTrials.gov ID
- NCT03136497
- Acronym / sponsor ID
- Pro00005671
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Hackensack Meridian HealthUniversity, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC, Genentech, Inc.
- Study start
- 5 Sep 2017 (actual)
- Primary completion
- 9 Nov 2020 (actual)
- Study completion
- 9 Nov 2020 (actual)
- First posted
- 2 May 2017 (actual)
- Results
- Posted 23 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Study of Venetoclax Plus Ibrutinib and Rituximab in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL).
Our hypothesis is that the combination therapy of BTK (Bruton's tyrosine kinase) Inhibitor Ibrutinib plus Venetoclax and Rituximab in relapsed or refractory DLBCL will have an increased activity with acceptable toxicity. Furthermore, this new novel therapeutic combination will be safe and well tolerated among this patient population.
Detailed description
This is a Phase 1b, single-arm, open-label, single-center study of venetoclax (ABT-199) in combination with ibrutinib and rituximab in Subjects with Relapsed/Refractory DLBCL. The trial consists of a dose-escalation of venetoclax in combination with standard doses of ibrutinib and rituximab. For the dose escalation part of the study, a standard 3+3 design will be utilized. Once the MTD has been established, the dose escalation part will be followed by a dose expansion part in a cohort with a maximum of 24 subjects with DLBCL. The purpose of the dose expansion part is to investigate the efficacy of the combination. Between the dose-escalation and dose-expansion, the maximum number of subjects will be 30.
Cycle length will be 28 days. Venetoclax will be administered orally QD (Once Daily), continuously for 24 cycles. Ibrutinib will be administered orally QD, continuously for 24 cycles. Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1), Commercially available rituximab IV will be used.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 400mg ABT-199 | Experimental | Drug: 400mg ABT-199, Drug: Ibrutinib, Drug: RituximabCycle length will be 28 days. 400mg ABT-199 will be administered orally QD (Once Daily), continuously for 24 cycles. Ibrutinib will be administered orally QD, continuously for 24 cycles. Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1), Commercially available rituximab IV will be used. |
| 800mg ABT-199 | Experimental | Drug: Ibrutinib, Drug: Rituximab, Drug: 800mg ABT-199Cycle length will be 28 days. 800mg ABT-199 will be administered orally QD (Once Daily), continuously for 24 cycles. Ibrutinib will be administered orally QD, continuously for 24 cycles. Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1), Commercially available rituximab IV will be used. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- ECOG (Eastern Cooperative Oncology Group) Performance Status </= 2.
- Histologically or cytologically confirmed diagnosis of advanced DLBCL.
- Ability and willingness to comply with the requirements of the study protocol
- Prior therapy: relapsed or refractory patients who have received one prior therapy are eligible. If treated with small molecule, washout therapy with a period of greater than 5 times the half-life of the molecule. Patients who have previously received high-dose chemotherapy with peripheral stem cell support are eligible. Washout period of 21 days.
- Presence of at least one lymph node evaluable or mass measurable for response.
Key exclusion criteria (27 listed)
- Known central nervous system lymphoma.
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon).
- Received the following agents within 7 days prior to the first dose of venetoclax or requires chronic treatment with strong Cytochrome P450 3A4 (CYP3A) inhibitors (e.g., ketoconazole, ritonavir, clarithromycin, itraconazole, voriconazole), moderate CYP3A inhibitors (e.g., erythromycin, ciprofloxacin, diltiazem, fluconazole, verapamil), strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine). (See Appendix 4)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 400mg ABT-199Also: A-1195425.0, VenetoclaxOral dose daily until disease progression | Drug | 400mg ABT-199 |
| IbrutinibAlso: PIC-32765, ImbruvicaOral dose daily until disease progression | Drug | 400mg ABT-199, 800mg ABT-199 |
| RituximabAlso: RituxanRituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1 | Drug | 400mg ABT-199, 800mg ABT-199 |
| 800mg ABT-199Also: A-1195425.0, VenetoclaxOral dose daily until disease progression | Drug | 800mg ABT-199 |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 29 days
Define maximum tolerated dose and /or recommended phase II dose for the combinations of venetoclax (ABT-199, GDC-0199) plus Ibrutinib (PCI-32765) and rituximab in Relapsed or Refractory DLBCL by assessing the incidence of dose limiting toxicities (DLTs).
3 secondary outcomes
Incidence of Treatment-emergent Adverse Events.
Time frame: 36 Months
Efficacy as Assessed by Progression Free Survival (PFS)
Time frame: 36 Months
Efficacy as Assessed by Overall Survival (OS)
Time frame: 36 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12493639Borner C. The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol. 2003 Jan;39(11):615-47. doi: 10.1016/s0161-5890(02)00252-3.
- Background: PubMed 7237385Binet JL, Auquier A, Dighiero G, Chastang C, Piguet H, Goasguen J, Vaugier G, Potron G, Colona P, Oberling F, Thomas M, Tchernia G, Jacquillat C, Boivin P, Lesty C, Duault MT, Monconduit M, Belabbes S, Gremy F. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981 Jul 1;48(1):198-206. doi: 10.1002/1097-0142(19810701)48:13.0.co;2-v.
- Background: PubMed 15384972Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol. 2004 Oct;127(1):3-11. doi: 10.1111/j.1365-2141.2004.05094.x.
- Background: PubMed 18362358Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM. MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5166-71. doi: 10.1073/pnas.0800121105. Epub 2008 Mar 24.
- Background: PubMed 17658394Catovsky D, Richards S, Matutes E, Oscier D, Dyer M, Bezares RF, Pettitt AR, Hamblin T, Milligan DW, Child JA, Hamilton MS, Dearden CE, Smith AG, Bosanquet AG, Davis Z, Brito-Babapulle V, Else M, Wade R, Hillmen P; UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group; NCRI Chronic Lymphocytic Leukaemia Working Group. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007 Jul 21;370(9583):230-239. doi: 10.1016/S0140-6736(07)61125-8.
- Background: PubMed 8652811Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S, Rai KR. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996 Jun 15;87(12):4990-7. No abstract available.
- Background: PubMed 25113753Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.
- Background: PubMed 11807147Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. doi: 10.1056/NEJMoa011795.
- Background: PubMed 20548096Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Ferme C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. doi: 10.1182/blood-2010-03-276246. Epub 2010 Jun 14.
- Background: PubMed 12209154Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002 Sep;2(9):647-56. doi: 10.1038/nrc883.
- Background: PubMed 14634621Cory S, Huang DC, Adams JM. The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene. 2003 Nov 24;22(53):8590-607. doi: 10.1038/sj.onc.1207102.
- Background: PubMed 20054396Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang Y, Xu W, Shaffer AL, Wright G, Xiao W, Powell J, Jiang JK, Thomas CJ, Rosenwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Connors JM, Johnson NA, Rimsza LM, Campo E, Jaffe ES, Wilson WH, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pierce SK, Staudt LM. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature. 2010 Jan 7;463(7277):88-92. doi: 10.1038/nature08638.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andre Goy, MD principal investigator
Hackensack Meridian Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 400mg ABT-199, Ibrutinib and Rituximab in people with Relapsed Diffuse Large B-Cell Lymphoma and Refractory Diffuse Large B-Cell Lymphoma, run by Hackensack Meridian Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: 29 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03136497, which also lists 45 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2024.