NCT05289687 — Daratumumab for Chemotherapy-Refractory Minimal Residual Disease in T Cell ALL · CancerIndex
Clinical trial · Interventional
Daratumumab for Chemotherapy-Refractory Minimal Residual Disease in T Cell ALL
A Phase II Study of Daratumumab-Hyaluronidase for Chemotherapy-Relapsed/Refractory Minimal Residual Disease (MRD) in T Cell Acute Lymphoblastic Leukemia (T-ALL
In this study, the investigators are hypothesizing that daratumumab-hyaluronidase will effectively treat T-ALL in patients who have persistent or recurrent MRD following treatment with chemotherapy.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
Requires that all of the following be present.
* Peripheral Blood Counts
* Neutrophil count ≥ 1,000/µL.
* Platelet count ≥ 100,000/µL.
* Reduced hemoglobin concentration or hematocrit has no bearing on remission status.
* Leukemic blasts must not be present in the peripheral blood.
* Bone Marrow Aspirate and Biopsy
* Cellularity of bone marrow biopsy must be \> 20% with maturation of all cell lines.
* ≤ 5% T lymphoblasts by flow cytometry.
* Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present.
measure
Complete Remission (CR)
timeFrame
Eligibility
Eligibility (as posted)
Sex
All
Minimum age
18 Years
Show eligibility criteria text
Inclusion Criteria:
* Patient must have documented T cell ALL and must be in first or later hematologic CR or CRi after a minimum of 2 blocks of intensive chemotherapy.
* Patients in hematologic CR or CRi must have persistent or recurrent MRD ≥ 10-4.
* Institution must have received central MRD status test results confirming persistent or recurrent MRD ≥ 10-4 by flow cytometry.
* Patient may have undergone a prior allogeneic stem cell transplant, but patient may not have Grafts Versus Host Disease (GVHD) that requires ongoing immunosuppressive therapy. Patient may receive prednisone if the dose is ≤ 10 mg per day.
* Patient must have an ECOG performance status 0-2.
* All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 registration to rule out pregnancy.
* Patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and continue to 3 months after the last dose of protocol treatment. Patients must also agree to abstain from donating sperm, even if they have had a successful vasectomy, or donating eggs while on study treatment and for 3 months after the last dose of protocol treatment.
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.
* Patient must have adequate organ and marrow function as defined below (these labs must be obtained ≤ 7 days prior to Step 1 registration).
* Absolute neutrophil count (ANC) ≥ 750/μL
* Platelets ≥ 75,000/μL
* Total or Direct bilirubin ≤ 2 mg/dL
* AST(SGOT)/ALT(SGPT) ≤ 3.0 × institutional ULN
* Creatinine ≤ 1.5 x institutional ULN or Creatinine Clearance \> 30 ml/min
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Patients with prior CNS involvement are eligible as long as they do not have active CNS involvement at time of Step 1 registration.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
Exclusion Criteria:
-Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
References
Publications (24)
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BACKGROUNDSteinherz PG, Gaynon PS, Breneman JC, Cherlow JM, Grossman NJ, Kersey JH, Johnstone HS, Sather HN, Trigg ME, Uckun FM, Bleyer WA. Treatment of patients with acute lymphoblastic leukemia with bulky extramedullary disease and T-cell phenotype or other poor prognostic features: randomized controlled trial from the Children's Cancer Group. Cancer. 1998 Feb 1;82(3):600-12. doi: 10.1002/(sici)1097-0142(19980201)82:33.0.co;2-4. PMID 9452280
BACKGROUNDMarks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, Ferrando A, Fielding AK, Goldstone AH, Ketterling RP, Litzow MR, Luger SM, McMillan AK, Mansour MR, Rowe JM, Tallman MS, Lazarus HM. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009 Dec 10;114(25):5136-45. doi: 10.1182/blood-2009-08-231217. PMID 19828704
BACKGROUNDSchrappe 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. PMID 21719599
Day 64
description
Requires that all of the following be present.
* Peripheral Blood Counts
* Neutrophil count ≥ 1,000/µL.
* Platelet count ≥ 100,000/µL.
* Reduced hemoglobin concentration or hematocrit has no bearing on remission status.
* Leukemic blasts must not be present in the peripheral blood.
* Bone Marrow Aspirate and Biopsy
* Cellularity of bone marrow biopsy must be \> 20% with maturation of all cell lines.
* ≤ 5% T lymphoblasts by flow cytometry.
* Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present.
measure
Complete Response with Partial Count Recovery (CRh)
timeFrame
Day 29
description
The same as for CR except with unsupported platelets \> 50,000/μL, hemoglobin \> 7 g/dL, and absolute neutrophil count \> 500/μL.
measure
Complete Response with Partial Count Recovery (CRh)
timeFrame
Day 64
description
The same as for CR except with unsupported platelets \> 50,000/μL, hemoglobin \> 7 g/dL, and absolute neutrophil count \> 500/μL.
measure
Complete Remission incomplete (CRi)
timeFrame
Day 29
description
All the same response criteria in peripheral blood and bone marrow as CR with the exception that there is incomplete platelet recovery (platelets \> 75,000/uL but \< 100,000/μL independent of platelet transfusions) or incomplete neutrophil count recovery \> 750/uL but \< 1000/μL.
measure
Complete Remission incomplete (CRi)
timeFrame
Day 64
description
All the same response criteria in peripheral blood and bone marrow as CR with the exception that there is incomplete platelet recovery (platelets \> 75,000/uL but \< 100,000/μL independent of platelet transfusions) or incomplete neutrophil count recovery \> 750/uL but \< 1000/μL.
measure
Minimal Residual Disease Negativity (MRD-)
timeFrame
Day 29
description
Bone marrow lymphoblast percent \< 0.01% (\< 10-4) by flow cytometry in a patient that fulfills count requirements for CR/CRh/CRi..
measure
Minimal Residual Disease Negativity (MRD-)
timeFrame
Day 64
description
Bone marrow lymphoblast percent \< 0.01% (\< 10-4) by flow cytometry in a patient that fulfills count requirements for CR/CRh/CRi..
measure
Morphologic Relapse
timeFrame
Day 29
description
Bone Marrow Aspirate and Biopsy
* Presence of \> 5% T lympho-blasts, not attributable to another cause (e.g., bone marrow regeneration).
* If there are no circulating blasts and the bone marrow contains 5% to 20% blasts, then a repeat bone marrow performed ≥ 1 week later documenting more than 5% blasts is necessary to meet the criteria for relapse.
measure
MRD Relapse
timeFrame
Day 29
description
• Relapse following MRD negativity is defined as bone marrow T lymphoblast percent ≥ 0.01% (10-4).
measure
Morphologic Relapse
timeFrame
Day 64
description
Bone Marrow Aspirate and Biopsy
* Presence of \> 5% T lympho-blasts, not attributable to another cause (e.g., bone marrow regeneration).
* If there are no circulating blasts and the bone marrow contains 5% to 20% blasts, then a repeat bone marrow performed ≥ 1 week later documenting more than 5% blasts is necessary to meet the criteria for relapse.
measure
MRD Relapse
timeFrame
Day 64
description
• Relapse following MRD negativity is defined as bone marrow T lymphoblast percent ≥ 0.01% (10-4).
measure
Refractory
timeFrame
Day 29
description
Failure to achieve MRD negativity as defined by bone marrow with CR/CRh/CRi with T lymphoblast percent ≥ 0.01% (10-4).
measure
Refractory
timeFrame
Day 64
description
Failure to achieve MRD negativity as defined by bone marrow with CR/CRh/CRi with T lymphoblast percent ≥ 0.01% (10-4).
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BACKGROUNDBruggemann 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. PMID 16195338
BACKGROUNDGokbuget 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. PMID 22442346
BACKGROUNDBrent L. Wood, Stuart S. Winter, Kimberly P. Dunsmore, Meenakshi Devidas, Si Chen, Barbara Asselin, Natia Esiashvili, Mignon L. Loh, Naomi J. Winick, William L. Carroll, Elizabeth A. Raetz SPH. T-lymphoblastic leukemia (T-ALL) shows excellent outcome, lack of significance of the early Thymic precursor (ETP) Immunophenotype, and validation of the prognostic value of end- induction minimal residual disease (MRD) in Children's oncology group (COG) Study AALL0434 Blood 2014;124.
BACKGROUNDWood BL, Winter SS, Dunsmore KP, Devidas M, Chen S, Asselin B, et al. Patients with early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL) have high levels of minimal residual disease (MRD) at the end of induction-a Children's oncology group (COG) study [abstract]. Blood. 2009;114.
BACKGROUNDQuist-Paulsen P, Toft N, Heyman M, Abrahamsson J, Griskevicius L, Hallbook H, Jonsson OG, Palk K, Vaitkeviciene G, Vettenranta K, Asberg A, Frandsen TL, Opdahl S, Marquart HV, Siitonen S, Osnes LT, Hultdin M, Overgaard UM, Wartiovaara-Kautto U, Schmiegelow K. T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol. Leukemia. 2020 Feb;34(2):347-357. doi: 10.1038/s41375-019-0598-2. Epub 2019 Oct 14. PMID 31611626
BACKGROUNDGokbuget 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. PMID 29358182
BACKGROUNDBride 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. PMID 29305553
BACKGROUNDVogiatzi F, Winterberg D, Lenk L, Buchmann S, Cario G, Schrappe M, Peipp M, Richter-Pechanska P, Kulozik AE, Lentes J, Bergmann AK, Valerius T, Frielitz FS, Kellner C, Schewe DM. Daratumumab eradicates minimal residual disease in a preclinical model of pediatric T-cell acute lymphoblastic leukemia. Blood. 2019 Aug 22;134(8):713-716. doi: 10.1182/blood.2019000904. Epub 2019 Jul 16. No abstract available. PMID 31311816
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