Marginal Zone LymphomaPhase 2NCT04508647
Ublituximab Followed by Response-driven Addition of Umbralisib for Treatment-naive Follicular or Marginal Zone Lymphoma
A Phase 2 study testing Ublituximab and Umbralisib in people with Marginal Zone Lymphoma and Follicular Lymphoma, run by University of Colorado, Denver at 1 site in United States.
Trial summary
This is an open-label, Phase II interventional study in order to assess efficacy and safety of single agent ublituximab as initial therapy for FL (Follicular lymphoma) and MZL (Marginal zone lymphoma ) with response driven addition of umbralisib for suboptimal response. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Marginal Zone Lymphoma, Follicular Lymphoma
- What is being tested?
- Ublituximab and Umbralisib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Nov 2020to 14 Jul 2022
- Phase
- Phase 2
- 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
- Disease Related
- Subjects with histologically documented Follicular lymphoma CD20+ (Grade 1, 2 or 3a) OR Marginal zone lymphoma CD20+ (nodal, extranodal or splenic) according to World Health Organization (WHO) criteria.
- Ann Arbor Stage II (Non-contiguous), III or IV disease
- Patients must have a whole body or limited whole body PET/CT scan performed within 42 days prior to registration. CT portion of PET/CT will be done with contrast based on current NCCN guidelines unless patient has borderline renal function or allergic to contrast dye.
- Patients must have bone marrow biopsy performed within 6 months prior to registration
- Measurable node must have an LDi greater than 1.5 cms. In the absence of nodal lesions, measurable extranodal disease should have an LDi greated than 1 cm. In patients with Splenic Marginal Zone lymphoma, in the absence of nodal lesions, spleen size should should be over 14 cms with evidence of lymphoma in the bone marrow biopsy.
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- For low tumor burden lymphomas (as determined by GELF criteria) : Include patients diagnosed within 2 years of diagnosis. Low tumor burden patients diagnosed more than 2 years from study entry will be allowed provided patients have documented progression.
- Prior Therapy Criteria
- 1. Patients must be untreated advanced stage disease (Stage III or Stage IV) or Stage II (noncontiguous). (Exception: Involved field or involved site radiation given for localized diagnosis is not considered a line of therapy).
- Clinical/Laboratory Criteria
- Patients must be ≥ 18 years of age and be able to swallow and retain oral medication
- ECOG performance status of 0-2
- Patients must have adequate bone marrow function as evidenced by ANC ≥ 1000/µL and platelets ≥ 50,000µL and Hb >= 8g/dl within 28 days prior to registration unsupported by growth factors.
- Serum creatinine < 2.0 mg/dL or calculated creatinine clearance (CrCl) > 45 mL/min
- Patients must have adequate hepatic function obtained within 28 days prior to registration and documented by all of the following:
- Total bilirubin ≤ 1.5 x IULN (≤ 5 x IULN if secondary to lymphoma, Gilbert's syndrome, or medication related)
- Direct bilirubin ≤ 1.5 x IULN (≤ 5 x IULN if secondary to lymphoma)
- AST and ALT ≤ 2.5 x IULN (≤ 5 x IULN secondary to lymphoma)
- Patients must be willing to receive Pneumocystis jirovecii prophylaxis with sulfamethoxazole/trimethoprim, dapsone, and atovaquone or inhaled pentamadine, if they initiate combination umbralisib plus ublituximab (not for single agent ublituximab)
- Patients must have a complete history and physical examination within 28 days prior to registration
- Patients with follicular lymphoma must have the following components of Follicular Lymphoma International Prognostic Index (FLIPI) available from diagnosis, and collected again at time of registration:
- Age
- LDH
- Number of nodal groups involved
- Serum or plasma hemoglobin
- Ann Arbor Stage Additionally, patients must have beta2-microglobulin collected at time of registration and response assessment.
- Female subjects of reproductive potential must have a negative serum pregnancy test within 3 days prior to treatment start date. Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy at least six weeks ago) are exempt from pregnancy testing. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
- Male and female subjects of reproductive potential who agree to use both a highly effective method of birth control (e.g., implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence, or sterilized partner) and a barrier method (e.g., condoms, cervical ring, sponge, etc.) during the period of therapy.
- The following are UNACCEPTABLE forms of contraception for females of childbearing potential:
- natural family planning (rhythm method)
- breastfeeding
- fertility awareness
- withdrawal For subjects, these birth control requirements must be adhered to for 4 months after the last dose of umbralisib and 12 months after the last dose of ublituximab, whichever is later.
- Regulatory Criteria
- 1. Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
Who cannot join
- Disease-Related
- Transformed lymphoma; if clinical evidence of transformed lymphoma is present, transformation should be ruled out by biopsy of the suspicious lymph node/lesion
- Prior treatment for follicular lymphoma or marginal zone lymphoma (Except: involved field or site radiation therapy is allowed)
- Medically apparent central nervous system lymphoma or leptomeningeal disease
- Tumor burden where administration of other FDA approved anti-CD20 antibodies like singleagent rituximab would be inappropriate.
- Patients in need of immediate cytoreduction with chemotherapy based regimen.
Show all 23Show fewer
- Concurrent Conditions
- Evidence of chronic active Hepatitis B (HBV, not including patients with prior hepatitis B vaccination; or positive serum Hepatitis B antibody) or chronic active Hepatitis C infection (HCV), active cytomegalovirus (CMV), or known history of HIV (or positive HIV test during screening). If HBc antibody is positive, the subject must be evaluated for the presence of HBV DNA by PCR. If HCV antibody is positive, the subject must be evaluated for the presence of HCV RNA by PCR. See Appendix: HEPATITIS B SEROLOGIC TEST RESULTS. If the subject is CMV IgG or CMV IgM positive, the subject must be evaluated for the presence of CMV DNA by PCR. Subjects with positive HBc antibody and negative HBV DNA by PCR are eligible. Subjects with positive HCV antibody and negative HCV RNA by PCR are eligible (subjects who are CMV IgG or CMV IgM positive but who are CMV DNA negative by PCR are eligible).
- Ongoing drug-induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by stones, or cirrhosis of the liver
- Inflammatory bowel disease (such as Crohn's disease or ulcerative colitis)
- Irritable bowel syndrome with greater than 3 loose stools per day as a baseline
- Active autoimmune disease requiring ongoing immunosuppressive therapy including systemic corticosteroids (prednisone or equivalent ≤10 mg daily allowed as clinically warranted) within 12 months prior to enrollment. Patients are allowed to use topical or inhaled corticosteroids or levothyroxine for hypothyroidism or hypogylcemic agents for diabetes mellitis.
- Any severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study such as:
- Symptomatic, or history of documented congestive heart failure NYHA (New York Heart Association) functional classification III-IV [see Appendix: New York Heart Association Classifications]
- Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, CHF, or myocardial infarction within 6 months of enrollment.
- Concomitant use of medication known to cause QT prolongation or torsades de pointes should be used with caution and at investigator discretion.
- Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac or vascular stenting within 6 months of enrollment.
- Women who are pregnant or lactating
- History of other malignancies (including myelodysplastic syndromes) except:
- malignancy treated with curative intent and with no known active disease present for >2 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician
- adequately treated non-melanoma skin cancer without evidence of disease
- adequately treated carcinoma in situ without evidence of disease
- localized prostate cancer and PSA <1.0 mg/dL on 2 consecutive measurements at least 3 months apart with the most recent one being within 4 weeks of study entry
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Hospital
Aurora, Colorado, 80045
About this study
Official title: Ublituximab as Initial Therapy for Treatment-naive Follicular or Marginal Zone Lymphoma With Response-driven Addition of Umbralisib for Suboptimal Response
This is an open-label, Phase II interventional study in order to assess efficacy and safety of single agent ublituximab as initial therapy for FL (Follicular lymphoma) and MZL (Marginal zone lymphoma ) with response driven addition of umbralisib for suboptimal response.
Read the detailed description
Based on overall reporting in low tumor burden FL and MZL, CR rate of at least 30% was achieved when single agent rituximab was used in these subsets. The investigators assume that by administering ublituximab (both as a single agent and in combination with umbralisib for individuals who fail to achieve a CR [Complete response] with the single agent), the CR rate will increase to 50%. Efficacy will be assessed using the proportion of patients treated with ublituximab alone or with ublituximab administered in combination who have a complete response. Thus, the investigators will test the efficacy of ublituximab using a difference in proportions design by comparing an expected study population control rate of 50% to the comparison proportion being determined by the historical control CR rate of 30%. In other words, the null hypothesis is that the true response rate is 30%, and it will be formally tested against a one-sided alternative that the response rate is 50%.
- Conditions
- Marginal Zone Lymphoma, Follicular Lymphoma
- Being tested
- Ublituximab, Umbralisib
- Medical subject headings
- Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UblituximabDrug
Ublituximab will be administered as an intravenous infusion through a dedicated line. All infusions will be administered per institutional guidelines.
During ublituximab monotherapy (initial treatment), Cycle 1 Day 1 administration time frame: Over 4 hours. Cycle 1 days 8 and 15 will be over 3 hours, and Cycle 1 Day 22 will be over 90 minutes. During combination treatment with umbralisib, ublituximab will be administered over 90 minutes.
UmbralisibDrug
Umbralisib will be administered orally once daily within 30 minutes of starting a meal.
| Study group | Role | What they receive |
|---|---|---|
| Ublituximab Only | Experimental | Treatment-Naive Stage II (non-contiguous), Stage III, Stage IV FL + MZL will receive Ublituximab 900mg IV weekly x 4 doses. End of treatment assessment 8 weeks post last dose of single agent ublituximab will be performed. Receives: Drug: Ublituximab |
| Ublituximab first, then Ublituximab and Umbralisib | Experimental | Patients who achieve less than a complete response will receive a combination of ublituximab AND umbralisib for a total of 12 cycles. (In the combination arm ublituximab will be administered on day 1,8 and 15 on cycle 1 and on day 1 on each cycle thereafter. Umbralisib will be administered at 800 mg daily for 12 cycles) Receives: Drug: Ublituximab; Drug: Umbralisib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Complete Response Rate (CR) at 8 Weeks Post Single Agent Induction
Number of subjects that reached a complete response at the end of single agent induction as defined by a Lugano score of 3 or less on arm MONO - Monotherapy: Ublituximab.
Complete response assessed via PET CT scan utilizing the Lugano-Deauville Criteria where none of the lymphoma lesions had FDG ( FluoroDeoxyglucose) avidity greater than the liver uptake.
Patients who did not reach complete response at this point were then bridged to arm COMBO - Combotherapy: Ublituximab + Umbralisib.
Measured: 8 weeks post induction
Number of Participants With Complete Response Rate (CR) at up to 12 Months Post MONO - Monotherapy: Ublituximab or Combotherapy: Ublituximab + Umbralisib.
Number of subjects that reached a complete response at up to 12 months post induction as defined by a Lugano score of 3 or less on arms MONO - Monotherapy: Ublituximab.OR Combotherapy: Ublituximab + Umbralisib.
Complete response assessed via PET CT scan utilizing the Lugano-Deauville Criteria where none of the lymphoma lesions had FDG ( FluoroDeoxyglucose) avidity greater than the liver uptake.
Measured: up to 12 months post induction
Secondary outcomes (1)
Overall Response Rates (ORR) for Number of Participants
Overall Response Rate for number of subjects as defined by a Lugano score of 3 or less on arms MONO - Monotherapy: Ublituximab.OR Combotherapy: Ublituximab + Umbralisib.
Overall response rate assessed via PET CT utilizing Lugano deauvile criteria where lymphoma lesions had responded and would include complete response, partial response (> 50% improvement) and stable disease (less than 50 % response)
Measured: up to 12 months post induction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2020
- Study start23 Nov 2020
- Primary completion14 Jul 2022
- Study completion14 Jul 2022
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 (33)Papers the sponsor has linked to this study.
- Other trials for Marginal Zone LymphomaStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Manali Kamdar, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04508647
- Sponsor's protocol ID
- 18-2128.cc
- Other IDs
- NCI-2021-00405, U2-NTG-009
- Status last verified
- Mar 2024
- First submitted
- 7 Aug 2020
- Last updated
- 21 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gribben JG. How I treat indolent lymphoma. Blood. 2007 Jun 1;109(11):4617-26. doi: 10.1182/blood-2006-10-041863. Epub 2007 Feb 20.
PubMed 17311989Kahl BS. Follicular lymphoma: are we ready for a risk-adapted approach? Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):358-364. doi: 10.1182/asheducation-2017.1.358.
PubMed 29222279Relander T, Johnson NA, Farinha P, Connors JM, Sehn LH, Gascoyne RD. Prognostic factors in follicular lymphoma. J Clin Oncol. 2010 Jun 10;28(17):2902-13. doi: 10.1200/JCO.2009.26.1693. Epub 2010 Apr 12.
PubMed 20385990Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011 May 12;117(19):5019-32. doi: 10.1182/blood-2011-01-293050. Epub 2011 Feb 7.
PubMed 21300984Horn H, Schmelter C, Leich E, Salaverria I, Katzenberger T, Ott MM, Kalla J, Romero M, Siebert R, Rosenwald A, Ott G. Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles. Haematologica. 2011 Sep;96(9):1327-34. doi: 10.3324/haematol.2011.042531. Epub 2011 Jun 9.
PubMed 21659362Link BK, Maurer MJ, Nowakowski GS, Ansell SM, Macon WR, Syrbu SI, Slager SL, Thompson CA, Inwards DJ, Johnston PB, Colgan JP, Witzig TE, Habermann TM, Cerhan JR. Rates and outcomes of follicular lymphoma transformation in the immunochemotherapy era: a report from the University of Iowa/MayoClinic Specialized Program of Research Excellence Molecular Epidemiology Resource. J Clin Oncol. 2013 Sep 10;31(26):3272-8. doi: 10.1200/JCO.2012.48.3990. Epub 2013 Jul 29.
PubMed 23897955Solal-Celigny P, Lepage E, Brousse N, Tendler CL, Brice P, Haioun C, Gabarre J, Pignon B, Tertian G, Bouabdallah R, Rossi JF, Doyen C, Coiffier B. Doxorubicin-containing regimen with or without interferon alfa-2b for advanced follicular lymphomas: final analysis of survival and toxicity in the Groupe d'Etude des Lymphomes Folliculaires 86 Trial. J Clin Oncol. 1998 Jul;16(7):2332-8. doi: 10.1200/JCO.1998.16.7.2332.
PubMed 9667247Solal-Celigny P. [Treatment of malignant low-grade lymphoma. Follicular Lymphoma Study Group]. Rev Med Interne. 1998;19 Suppl 1:18S-20S. doi: 10.1016/s0248-8663(98)80005-2. No abstract available. French.
PubMed 9789523Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, Pro B, Pileri S, Pulsoni A, Soubeyran P, Cortelazzo S, Martinelli G, Martelli M, Rigacci L, Arcaini L, Di Raimondo F, Merli F, Sabattini E, McLaughlin P, Solal-Celigny P. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol. 2009 Sep 20;27(27):4555-62. doi: 10.1200/JCO.2008.21.3991. Epub 2009 Aug 3.
PubMed 19652063Pastore A, Jurinovic V, Kridel R, Hoster E, Staiger AM, Szczepanowski M, Pott C, Kopp N, Murakami M, Horn H, Leich E, Moccia AA, Mottok A, Sunkavalli A, Van Hummelen P, Ducar M, Ennishi D, Shulha HP, Hother C, Connors JM, Sehn LH, Dreyling M, Neuberg D, Moller P, Feller AC, Hansmann ML, Stein H, Rosenwald A, Ott G, Klapper W, Unterhalt M, Hiddemann W, Gascoyne RD, Weinstock DM, Weigert O. Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol. 2015 Sep;16(9):1111-1122. doi: 10.1016/S1470-2045(15)00169-2. Epub 2015 Aug 6.
PubMed 26256760Friedberg JW, Taylor MD, Cerhan JR, Flowers CR, Dillon H, Farber CM, Rogers ES, Hainsworth JD, Wong EK, Vose JM, Zelenetz AD, Link BK. Follicular lymphoma in the United States: first report of the national LymphoCare study. J Clin Oncol. 2009 Mar 10;27(8):1202-8. doi: 10.1200/JCO.2008.18.1495. Epub 2009 Feb 9.
PubMed 19204203Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade non-Hodgkin's lymphomas. N Engl J Med. 1984 Dec 6;311(23):1471-5. doi: 10.1056/NEJM198412063112303.
PubMed 6548796Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: eastern cooperative oncology group protocol e4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. doi: 10.1200/JCO.2014.56.5853. Epub 2014 Aug 25.
PubMed 25154829Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, Lopez-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, Andre M, Zachee P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. doi: 10.1056/NEJMoa1805104.
PubMed 30184451Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grunhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Durk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Apr 6;381(9873):1203-10. doi: 10.1016/S0140-6736(12)61763-2. Epub 2013 Feb 20.
PubMed 23433739
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ublituximab as Initial Therapy for Treatment-naive Follicular or Marginal Zone Lymphoma With Response-driven Addition of Umbralisib for Suboptimal Response
- ClinicalTrials.gov ID
- NCT04508647
- Acronym / sponsor ID
- 18-2128.cc
- Conditions
- Marginal Zone Lymphoma, Follicular Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 23 Nov 2020 (actual)
- Primary completion
- 14 Jul 2022 (actual)
- Study completion
- 14 Jul 2022 (actual)
- First posted
- 11 Aug 2020 (actual)
- Results
- Posted 9 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, Phase II interventional study in order to assess efficacy and safety of single agent ublituximab as initial therapy for FL (Follicular lymphoma) and MZL (Marginal zone lymphoma ) with response driven addition of umbralisib for suboptimal response.
Detailed description
Based on overall reporting in low tumor burden FL and MZL, CR rate of at least 30% was achieved when single agent rituximab was used in these subsets. The investigators assume that by administering ublituximab (both as a single agent and in combination with umbralisib for individuals who fail to achieve a CR [Complete response] with the single agent), the CR rate will increase to 50%. Efficacy will be assessed using the proportion of patients treated with ublituximab alone or with ublituximab administered in combination who have a complete response. Thus, the investigators will test the efficacy of ublituximab using a difference in proportions design by comparing an expected study population control rate of 50% to the comparison proportion being determined by the historical control CR rate of 30%. In other words, the null hypothesis is that the true response rate is 30%, and it will be formally tested against a one-sided alternative that the response rate is 50%.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ublituximab Only | Experimental | Drug: UblituximabTreatment-Naive Stage II (non-contiguous), Stage III, Stage IV FL + MZL will receive Ublituximab 900mg IV weekly x 4 doses. End of treatment assessment 8 weeks post last dose of single agent ublituximab will be performed. |
| Ublituximab first, then Ublituximab and Umbralisib | Experimental | Drug: Ublituximab, Drug: UmbralisibPatients who achieve less than a complete response will receive a combination of ublituximab AND umbralisib for a total of 12 cycles. (In the combination arm ublituximab will be administered on day 1,8 and 15 on cycle 1 and on day 1 on each cycle thereafter. Umbralisib will be administered at 800 mg daily for 12 cycles) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (35 listed)
- Disease Related
- Subjects with histologically documented Follicular lymphoma CD20+ (Grade 1, 2 or 3a) OR Marginal zone lymphoma CD20+ (nodal, extranodal or splenic) according to World Health Organization (WHO) criteria.
- Ann Arbor Stage II (Non-contiguous), III or IV disease
- Patients must have a whole body or limited whole body PET/CT scan performed within 42 days prior to registration. CT portion of PET/CT will be done with contrast based on current NCCN guidelines unless patient has borderline renal function or allergic to contrast dye.
- Patients must have bone marrow biopsy performed within 6 months prior to registration
Key exclusion criteria (23 listed)
- Disease-Related
- Transformed lymphoma; if clinical evidence of transformed lymphoma is present, transformation should be ruled out by biopsy of the suspicious lymph node/lesion
- Prior treatment for follicular lymphoma or marginal zone lymphoma (Except: involved field or site radiation therapy is allowed)
- Medically apparent central nervous system lymphoma or leptomeningeal disease
- Tumor burden where administration of other FDA approved anti-CD20 antibodies like singleagent rituximab would be inappropriate.
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 |
|---|---|---|
| UblituximabUblituximab will be administered as an intravenous infusion through a dedicated line. All infusions will be administered per institutional guidelines. During ublituximab monotherapy (initial treatment), Cycle 1 Day 1 administration time frame: Over 4 hours. Cycle 1 days 8 and 15 will be over 3 hours, and Cycle 1 Day 22 will be over 90 minutes. During combination treatment with umbralisib, ublituximab will be administered over 90 minutes. | Drug | Ublituximab Only, Ublituximab first, then Ublituximab and Umbralisib |
| UmbralisibUmbralisib will be administered orally once daily within 30 minutes of starting a meal. | Drug | Ublituximab first, then Ublituximab and Umbralisib |
Primary outcome
Number of Participants With Complete Response Rate (CR) at 8 Weeks Post Single Agent Induction
Time frame: 8 weeks post induction
Number of subjects that reached a complete response at the end of single agent induction as defined by a Lugano score of 3 or less on arm MONO - Monotherapy: Ublituximab. Complete response assessed via PET CT scan utilizing the Lugano-Deauville Criteria where none of the lymphoma lesions had FDG ( FluoroDeoxyglucose) avidity greater than the liver uptake. Patients who did not reach complete response at this point were then bridged to arm COMBO - Combotherapy: Ublituximab + Umbralisib.
Number of Participants With Complete Response Rate (CR) at up to 12 Months Post MONO - Monotherapy: Ublituximab or Combotherapy: Ublituximab + Umbralisib.
Time frame: up to 12 months post induction
Number of subjects that reached a complete response at up to 12 months post induction as defined by a Lugano score of 3 or less on arms MONO - Monotherapy: Ublituximab.OR Combotherapy: Ublituximab + Umbralisib. Complete response assessed via PET CT scan utilizing the Lugano-Deauville Criteria where none of the lymphoma lesions had FDG ( FluoroDeoxyglucose) avidity greater than the liver uptake.
1 secondary outcome
Overall Response Rates (ORR) for Number of Participants
Time frame: up to 12 months post induction
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17311989Gribben JG. How I treat indolent lymphoma. Blood. 2007 Jun 1;109(11):4617-26. doi: 10.1182/blood-2006-10-041863. Epub 2007 Feb 20.
- Background: PubMed 29222279Kahl BS. Follicular lymphoma: are we ready for a risk-adapted approach? Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):358-364. doi: 10.1182/asheducation-2017.1.358.
- Background: PubMed 20385990Relander T, Johnson NA, Farinha P, Connors JM, Sehn LH, Gascoyne RD. Prognostic factors in follicular lymphoma. J Clin Oncol. 2010 Jun 10;28(17):2902-13. doi: 10.1200/JCO.2009.26.1693. Epub 2010 Apr 12.
- Background: PubMed 21300984Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011 May 12;117(19):5019-32. doi: 10.1182/blood-2011-01-293050. Epub 2011 Feb 7.
- Background: PubMed 21659362Horn H, Schmelter C, Leich E, Salaverria I, Katzenberger T, Ott MM, Kalla J, Romero M, Siebert R, Rosenwald A, Ott G. Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles. Haematologica. 2011 Sep;96(9):1327-34. doi: 10.3324/haematol.2011.042531. Epub 2011 Jun 9.
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- 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.
Manali Kamdar, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ublituximab and Umbralisib in people with Marginal Zone Lymphoma and Follicular Lymphoma, run by University of Colorado, Denver 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 35 inclusion and 23 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: finished, as of the sponsor's last update on 21 Mar 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 9 Nov 2023). 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?
Number of Participants With Complete Response Rate (CR) at 8 Weeks Post Single Agent Induction (time frame: 8 weeks post induction). The study lists 2 primary outcomes in all. 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 NCT04508647, which also lists 33 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 21 Mar 2024.