Daratumumab for Chemotherapy-Refractory Minimal Residual Disease in T Cell ALL

Официальное название

A Phase II Study of Daratumumab-Hyaluronidase for Chemotherapy-Relapsed/Refractory Minimal Residual Disease (MRD) in T Cell Acute Lymphoblastic Leukemia (T-ALL

Обзор

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.

Подробное описание

The primary hypothesis is that daratumumab-hyaluronidase will effectively eliminate chemotherapy refractory and relapsed MRD in T-ALL. The secondary hypotheses include; daratumumab-hyaluronidase will improve hematologic relapse free survival (RFS),daratumumab-hyaluronidase will improve overall survival (OS), patients that achieve complete MRD response with daratumumab will have improved survival outcomes, and daratumumab-hyaluronidase will be well tolerated in T-ALL after allogenic stem cell transplant.

The primary objective of this study is to evaluate the rate of complete MRD response by flow cytometry after 4 weekly doses of daratumumab-hyaluronidase (Day 29) among patients with MRD positive T-ALL in hematologic morphologic complete remission or complete remission with incomplete hematologic recovery. The secondary objectives include; evaluation of morphologic relapse free survival (RFS), evaluation of overall survival (OS), assessment of the the survival outcomes in patients that undergo allogeneic stem cell transplant after complete MRD response with daratumumab-hyaluronidase, assessment of adverse effects and tolerability of daratumumab-hyaluronidase in T-ALL, and assessment of flow cytometry based MRD status on Day 64 of treatment or upon count recovery for patients that receive chemotherapy in addition to daratumumab-hyaluronidase during Course 1A.

Вмешательства

• Препарат Daratumumab / Hyaluronidase Injection
  Daratumumab-hyaluronidase 1800mg/ 30,000 units once weekly for 4 doses on Days 1, 8, 15, and 22
• Препарат Daratumumab / Hyaluronidase Injection
  Patients that are MRD Negative on Day 29 will receive daratumumab-hyaluronidase 1800mg/ 30,000 units once weekly for 4 doses on Days 36, 43, 50, and 57.
• Препарат Daratumumab / Hyaluronidase Injection
  Patients that remain MRD positive on Day 29 will receive a combination of daratumumab-hyaluronidase 1800mg/ 30,000 units once weekly for 4 doses on Days 36, 43, 50, and 57 and chemotherapy selected from the combinations listed below: * Cytarabine 3000 mg/m2, IV, Every 12 hours for 4 doses on Days 37 and 38 * Methotrexate 1000 mg/m2, IV, Over 24 hours on Day 36 OR * Methotrexate, Starting dose 100 mg/m2, IV, Days 36, 46, 56 * Vincristine, 1.5 mg/m2 (2 mg cap), IV, Days 36, 46, 56 * Pegaspargas
• Препарат Daratumumab / Hyaluronidase Injection
  All patients with MRD negative response after completion of previous course are eligible for daratumumab-hyaluronidase 1800mg/ 30,000 units every 2 weeks on Days 1,15, 29, 43, 57, 71, 85, and 99 for 8 doses.

Первичные конечные точки

• Complete Remission (CR) [Срок оценки: Day 29]
• Complete Remission (CR) [Срок оценки: Day 64]
• Complete Response with Partial Count Recovery (CRh) [Срок оценки: Day 29]
• Complete Response with Partial Count Recovery (CRh) [Срок оценки: Day 64]
• Complete Remission incomplete (CRi) [Срок оценки: Day 29]
• Complete Remission incomplete (CRi) [Срок оценки: Day 64]
• Minimal Residual Disease Negativity (MRD-) [Срок оценки: Day 29]
• Minimal Residual Disease Negativity (MRD-) [Срок оценки: Day 64]
• Morphologic Relapse [Срок оценки: Day 29]
• MRD Relapse [Срок оценки: Day 29]

Критерии участия

Критерии включения

• 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.

Критерии исключения

-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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Northwestern — Chicago

Публикации

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• Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, Reaman GH, Carroll WL. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. J Clin Oncol. 2012 May 10;30(14):1663-9. doi: 10.1200/JCO.2011.37.8018. Epub 2012 Mar 12. PMID 22412151
• Steinherz 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( PMID 9452280
• Marks 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) PMID 19828704
• 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 A PMID 21719599
• Beldjord K, Chevret S, Asnafi V, Huguet F, Boulland ML, Leguay T, Thomas X, Cayuela JM, Grardel N, Chalandon Y, Boissel N, Schaefer B, Delabesse E, Cave H, Chevallier P, Buzyn A, Fest T, Reman O, Vernant JP, Lheritier V, Bene MC, Lafage M, Macintyre E, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Oncogenetics and minimal residual disease are independent ou PMID 24740809
• 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. PMID 16195338
• 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 PMID 22442346

Идентификаторы

NCT: NCT05289687 · EA9213

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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