Use of a New Medicine "Daratumumab" to Treat Left-over Cancer in a Blood Cancer Called "T Acute Lymphoblastic Leukemia"

Summary

T-ALL (T-acute lymphoblastic leukemia) is an aggressive blood cancer, wherein patients who are MRD positive after two courses of induction chemotherapy have poor outcomes. This goal of this study is to determine if Daratumumab can make such T-ALL patients MRD negative. The main questions this study aims to answer are - 1. Whether MRD Positive T-ALL patients can become MRD negative after two doses of daratumumab? 2. Whether MRD Positive T-ALL patients can become MRD negative after four doses of daratumumab? 3. Whether addition of daratumumab can affect the risk of progression or death at 1-year? 4. Whether daratumumab is safe to use? Newly diagnosed patients of T-ALL who are MRD positive after two courses of induction chemotherapy will be eligible to receive daratumumab. These patients will receive two doses of weekly intravenous daratumumab at standard dose (16mg/kg), and will undergo repeat evaluation of MRD from bone marrow one week after the second dose of daratumumab. Patients who become MRD negative will continue chemotherapy as per institutional policy. Those who remain MRD positive will be eligible to receive two additional doses, and will undergo another bone marrow MRD testing one week after the fourth dose. Irrespective of the results after the fourth dose, patients will be continued on chemotherapy as per institutional policy.

Timeline

Start

2023-08-28

Primary completion

2026-08-28

Completion

2026-08-28

Publications

• Results Usmani SZ, Weiss BM, Plesner T, Bahlis NJ, Belch A, Lonial S, Lokhorst HM, Voorhees PM, Richardson PG, Chari A, Sasser AK, Axel A, Feng H, Uhlar CM, Wang J, Khan I, Ahmadi T, Nahi H. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood. 2016 Jul 7;128(1):37-44. doi: 10.1182/blood-2016-03-705210. Epub 2016 May 23.
• Results Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, Minnema MC, Lassen U, Krejcik J, Palumbo A, van de Donk NW, Ahmadi T, Khan I, Uhlar CM, Wang J, Sasser AK, Losic N, Lisby S, Basse L, Brun N, Richardson PG. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma. N Engl J Med. 2015 Sep 24;373(13):1207-19. doi: 10.1056/NEJMoa1506348. Epub 2015 Aug 26.
• Results Lancman G, Arinsburg S, Jhang J, Cho HJ, Jagannath S, Madduri D, Parekh S, Richter J, Chari A. Blood Transfusion Management for Patients Treated With Anti-CD38 Monoclonal Antibodies. Front Immunol. 2018 Nov 15;9:2616. doi: 10.3389/fimmu.2018.02616. eCollection 2018.
• Results Blair HA. Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Drugs. 2017 Dec;77(18):2013-2024. doi: 10.1007/s40265-017-0837-7.
• Results Michaleas S, Penninga E, Hovgaard D, Dalseg AM, Rosso A, Sarac SB, Jimenez JC, Fernandez LL, Fernandez CP, Mangas-SanJuan V, Garcia I, Payares-Herrera C, Sancho-Lopez A, Enzmann H, de Castro Lopes Silva MSS, Duarte S, Pignatti F. EMA Review of Daratumumab (Darzalex) for the Treatment of Adult Patients Newly Diagnosed with Multiple Myeloma. Oncologist. 2020 Dec;25(12):1067-1074. doi: 10.1002/onco.13554. Epub 2020 Oct 16.
• Results Mirgh S, Sharma A, Folbs B, Khushoo V, Kapoor J, Tejwani N, Ahmed R, Agrawal N, Choudhary PS, Mehta P, Bhurani D. Daratumumab-based therapy after prior Azacytidine-Venetoclax in an octagenerian female with BPDCN (blastic plasmacytoid dendritic cell neoplasm) - a new perspective. Leuk Lymphoma. 2021 Dec;62(12):3039-3042. doi: 10.1080/10428194.2021.1941938. Epub 2021 Jun 21. No abstract available.
• Results Huang H, Zhu J, Yao M, Kim TM, Yoon DH, Cho SG, Eom HS, Lim ST, Yeh SP, Song Y, Kwong YL, Kim JS, Jin J, Shi Y, Kim H, Qing M, Zhou T, Gao G, Dong Z, Qi M, Kim WS. Daratumumab monotherapy for patients with relapsed or refractory natural killer/T-cell lymphoma, nasal type: an open-label, single-arm, multicenter, phase 2 study. J Hematol Oncol. 2021 Feb 15;14(1):25. doi: 10.1186/s13045-020-01020-y.
• Results Jeyaraman P, Borah P, Rajput P, Dayal N, Pathak S, Naithani R. Daratumumab for pure red cell aplasia post ABO incompatible allogeneic hematopoietic stem cell transplant for aplastic anemia. Blood Cells Mol Dis. 2021 May;88:102464. doi: 10.1016/j.bcmd.2020.102464. Epub 2020 Jul 2.
• Results Palladini G, Kastritis E, Maurer MS, Zonder J, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Bumma N, Kaufman JL, Medvedova E, Kovacsovics T, Rosenzweig M, Sanchorawala V, Qin X, Vasey SY, Weiss BM, Vermeulen J, Merlini G, Comenzo RL. Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Blood. 2020 Jul 2;136(1):71-80. doi: 10.1182/blood.2019004460.
• Results Cerrano M, Bonifacio M, Olivi M, Curti A, Malagola M, Dargenio M, Scattolin AM, Papayannidis C, Forghieri F, Gurrieri C, Tanasi I, Zappasodi P, La Starza R, Fracchiolla NS, Chiusolo P, Giaccone L, Del Principe MI, Giglio F, Defina M, Favre C, Rizzari C, Castella B, Pizzolo G, Ferrara F, Chiaretti S, Foa R. Daratumumab with or without chemotherapy in relapsed and refractory acute lymphoblastic leukemia. A retrospective observational Campus ALL study. Haematologica. 2022 Apr 1;107(4):996-999. doi: 10.3324/haematol.2021.279851. No abstract available.
• Results Punatar S, Gokarn A, Nayak L, Bonda A, Chichra A, Mirgh S, Bagal B, Tembhare P, Subramanian P, Khattry N. Long term outcome of a patient with relapsed refractory early thymic precursor acute lymphoblastic leukemia treated with daratumumab. Am J Blood Res. 2021 Oct 15;11(5):528-533. eCollection 2021.
• Results Li Z et al. Daratumumab regimen in treatment of relapsed hematological malignancies in children after allo-HSCT. APBMT 2020 (Oral-535)
• Results Brammer JE, Saliba RM, Jorgensen JL, Ledesma C, Gaballa S, Poon M, Maziarz RT, Champlin RE, Hosing C, Kebriaei P. Multi-center analysis of the effect of T-cell acute lymphoblastic leukemia subtype and minimal residual disease on allogeneic stem cell transplantation outcomes. Bone Marrow Transplant. 2017 Jan;52(1):20-27. doi: 10.1038/bmt.2016.194. Epub 2016 Sep 12.
• Results Shen Z, Gu X, Mao W, Yin L, Yang L, Zhang Z, Liu K, Wang L, Huang Y. Influence of pre-transplant minimal residual disease on prognosis after Allo-SCT for patients with acute lymphoblastic leukemia: systematic review and meta-analysis. BMC Cancer. 2018 Jul 23;18(1):755. doi: 10.1186/s12885-018-4670-5.
• Results Rajendra A, Jain H, Bonda VNA, Nayak L, Tembhare P, Shetty D, Thorat J, Jain H, Subramanian PG, Patkar N, Chatterjee G, Khattry N, Gokarn A, Punatar S, Mokal S, Bagal B, Sengar M. Outcomes and prognostic factors in adolescents and young adults with ALL treated with a modified BFM-90 protocol. Blood Adv. 2021 Mar 9;5(5):1178-1193. doi: 10.1182/bloodadvances.2020003526.
• Results Gokbuget N, Kneba M, Raff T, Trautmann H, Bartram CR, Arnold R, Fietkau R, Freund M, Ganser A, Ludwig WD, Maschmeyer G, Rieder H, Schwartz S, Serve H, Thiel E, Bruggemann M, Hoelzer D; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012 Aug 30;120(9):1868-76. doi: 10.1182/blood-2011-09-377713. Epub 2012 Mar 22.
• Results Cerrano M, Castella B, Lia G, Olivi M, Faraci DG, Butera S, Martella F, Scaldaferri M, Cattel F, Boccadoro M, Massaia M, Ferrero D, Bruno B, Giaccone L. Immunomodulatory and clinical effects of daratumumab in T-cell acute lymphoblastic leukaemia. Br J Haematol. 2020 Oct;191(1):e28-e32. doi: 10.1111/bjh.16960. Epub 2020 Jul 19. No abstract available.
• Results Ofran Y, Ringelstein-Harlev S, Slouzkey I, Zuckerman T, Yehudai-Ofir D, Henig I, Beyar-Katz O, Hayun M, Frisch A. Daratumumab for eradication of minimal residual disease in high-risk advanced relapse of T-cell/CD19/CD22-negative acute lymphoblastic leukemia. Leukemia. 2020 Jan;34(1):293-295. doi: 10.1038/s41375-019-0548-z. Epub 2019 Aug 21. No abstract available.
• Results Mirgh S, Ahmed R, Agrawal N, Khushoo V, Garg A, Francis S, Tejwani N, Singh N, Bhurani D. Will Daratumumab be the next game changer in early thymic precursor-acute lymphoblastic leukaemia? Br J Haematol. 2019 Oct;187(2):e33-e35. doi: 10.1111/bjh.16154. Epub 2019 Aug 26. No abstract available.
• Results Bonda A, Punatar S, Gokarn A, Mohite A, Shanmugam K, Nayak L, Bopanna M, Cheriyalinkal Parambil B, Khattry N. Daratumumab at the frontiers of post-transplant refractory T-acute lymphoblastic leukemia-a worthwhile strategy? Bone Marrow Transplant. 2018 Nov;53(11):1487-1489. doi: 10.1038/s41409-018-0222-5. Epub 2018 Jun 8. No abstract available.
• Results Bride KL, Vincent TL, Im SY, Aplenc R, Barrett DM, Carroll WL, Carson R, Dai Y, Devidas M, Dunsmore KP, Fuller T, Glisovic-Aplenc T, Horton TM, Hunger SP, Loh ML, Maude SL, Raetz EA, Winter SS, Grupp SA, Hermiston ML, Wood BL, Teachey DT. Preclinical efficacy of daratumumab in T-cell acute lymphoblastic leukemia. Blood. 2018 Mar 1;131(9):995-999. doi: 10.1182/blood-2017-07-794214. Epub 2018 Jan 5.
• Results Tembhare PR, Sriram H, Khanka T, Chatterjee G, Panda D, Ghogale S, Badrinath Y, Deshpande N, Patkar NV, Narula G, Bagal B, Jain H, Sengar M, Khattry N, Banavali S, Gujral S, Subramanian PG. Flow cytometric evaluation of CD38 expression levels in the newly diagnosed T-cell acute lymphoblastic leukemia and the effect of chemotherapy on its expression in measurable residual disease, refractory disease and relapsed disease: an implication for anti-CD38 immunotherapy. J Immunother Cancer. 2020 May;8(1):e000630. doi: 10.1136/jitc-2020-000630.
• Results Giri S, Grimshaw A, Bal S, Godby K, Kharel P, Djulbegovic B, Dimopoulos MA, Facon T, Usmani SZ, Mateos MV, Costa LJ. Evaluation of Daratumumab for the Treatment of Multiple Myeloma in Patients With High-risk Cytogenetic Factors: A Systematic Review and Meta-analysis. JAMA Oncol. 2020 Nov 1;6(11):1759-1765. doi: 10.1001/jamaoncol.2020.4338.
• Results Gokbuget N, Zugmaier G, Dombret H, Stein A, Bonifacio M, Graux C, Faul C, Bruggemann M, Taylor K, Mergen N, Reichle A, Horst HA, Havelange V, Topp MS, Bargou RC. Curative outcomes following blinatumomab in adults with minimal residual disease B-cell precursor acute lymphoblastic leukemia. Leuk Lymphoma. 2020 Nov;61(11):2665-2673. doi: 10.1080/10428194.2020.1780583. Epub 2020 Jul 3.
• Results Gokbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Bruggemann M, Horst HA, Havelange V, Stieglmaier J, Wessels H, Haddad V, Benjamin JE, Zugmaier G, Nagorsen D, Bargou RC. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018 Apr 5;131(14):1522-1531. doi: 10.1182/blood-2017-08-798322. Epub 2018 Jan 22.
• Results Schrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grumayer R, Moricke A, Parasole R, Zimmermann M, Dworzak M, Buldini B, Reiter A, Basso G, Klingebiel T, Messina C, Ratei R, Cazzaniga G, Koehler R, Locatelli F, Schafer BW, Arico M, Welte K, van Dongen JJ, Gadner H, Biondi A, Conter V. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood. 2011 Aug 25;118(8):2077-84. doi: 10.1182/blood-2011-03-338707. Epub 2011 Jun 30.
• Results Raetz EA, Teachey DT. T-cell acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2016 Dec 2;2016(1):580-588. doi: 10.1182/asheducation-2016.1.580.
• Results Tembhare P, Narula G, Chatterjee G, Khanka T, Sanyal M, et al. Flow-Cytometry Based Detection of Any Minimal Residual Disease (FC-MRD) in Children with T-Acute Lymphoblastic Leukemias (T-ALL) Is a Powerful Indicator of Outcome. Blood 2019; 134 (Supplement_1): 2585. doi: https://doi.org/10.1182/blood-2019-128347
• Results Bassan R, Spinelli O, Oldani E, Intermesoli T, Tosi M, Peruta B, Rossi G, Borlenghi E, Pogliani EM, Terruzzi E, Fabris P, Cassibba V, Lambertenghi-Deliliers G, Cortelezzi A, Bosi A, Gianfaldoni G, Ciceri F, Bernardi M, Gallamini A, Mattei D, Di Bona E, Romani C, Scattolin AM, Barbui T, Rambaldi A. Improved risk classification for risk-specific therapy based on the molecular study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia (ALL). Blood. 2009 Apr 30;113(18):4153-62. doi: 10.1182/blood-2008-11-185132. Epub 2009 Jan 13.
• Results Bruggemann M, Raff T, Flohr T, Gokbuget N, Nakao M, Droese J, Luschen S, Pott C, Ritgen M, Scheuring U, Horst HA, Thiel E, Hoelzer D, Bartram CR, Kneba M; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006 Feb 1;107(3):1116-23. doi: 10.1182/blood-2005-07-2708. Epub 2005 Sep 29.
• Results Litzow MR, Ferrando AA. How I treat T-cell acute lymphoblastic leukemia in adults. Blood. 2015 Aug 13;126(7):833-41. doi: 10.1182/blood-2014-10-551895. Epub 2015 May 12.
• Results Berry DA, Zhou S, Higley H, Mukundan L, Fu S, Reaman GH, Wood BL, Kelloff GJ, Jessup JM, Radich JP. Association of Minimal Residual Disease With Clinical Outcome in Pediatric and Adult Acute Lymphoblastic Leukemia: A Meta-analysis. JAMA Oncol. 2017 Jul 13;3(7):e170580. doi: 10.1001/jamaoncol.2017.0580. Epub 2017 Jul 13.
• Results van Dongen JJ, van der Velden VH, Bruggemann M, Orfao A. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies. Blood. 2015 Jun 25;125(26):3996-4009. doi: 10.1182/blood-2015-03-580027. Epub 2015 May 21.

Drugs

Indications