Inotuzumab Ozogamicin and Chemotherapy in Treating Patients With Leukemia or Lymphoma Undergoing Stem Cell Transplantation
Ключови думи
Резюме
Описание
PRIMARY OBJECTIVE:
I. To assess the safety of the addition of inotuzumab ozogamicin (IO) pre- and post-allogeneic transplantation in patients with CD22-positive hematological malignancies.
SECONDARY OBJECTIVES:
I. Overall survival, progression-free survival and relapse rates. II. Treatment-related mortality. III. Cumulative incidence of acute and chronic graft-versus-host disease (GVHD).
OUTLINE: Patients are assigned to 1 of 2 groups.
GROUP I: Patients with acute lymphoblastic leukemia (ALL) receive inotuzumab ozogamicin intravenously (IV) over 1 hour on day -13, fludarabine IV over 1 hour on days -5 to -2, melphalan IV over 30 minutes on day -2, and tacrolimus IV continuously beginning on day -2 then orally (PO) once daily (QD) or twice daily (BID) for about 6 months. Patients receiving stem cells from a matched unrelated donor (MUD), receive anti-thymocyte globulin IV over 3-4 hours on days -2 to -1 and not receive chemotherapy drugs. Patients also receive bone marrow or peripheral blood progenitor cells IV on day 0. Patients then receive methotrexate IV over 30 minutes on days 1, 3, 6, and 11 and filgrastim-sndz subcutaneously (SC) QD beginning 1 week after the transplant until blood cell levels return to normal. Patients with CD22-positive cancer, receive rituximab IV over 4-6 hours on days 1 and 8.
GROUP II: Patients with lymphoma receive inotuzumab ozogamicin IV over 1 hour on day -13, fludarabine IV over 1 hour and bendamustine IV over 30 minutes to 1 hour on days -5 to -3, and tacrolimus IV continuously beginning on day -2 then PO QD or BID for about 6 months. Patients receiving stem cells from a MUD, receive anti-thymocyte globulin IV over 3-4 hours on days -2 to -1 and not receive chemotherapy drugs. Patients also receive bone marrow or peripheral blood progenitor cells IV on day 0. Patients then receive rituximab IV over 4-6 hours on days 1 and 8, methotrexate IV over 30 minutes on days 1, 3, and 6, and filgrastim-sndz SC once a day beginning 1 week after the transplant. Patients who received a stem cell transplant from a MUD also receive methotrexate IV over 30 minutes on day 11.
MAINTENANCE: Between 45 and 100 days after stem cell transplantation, all patients receive inotuzumab ozogamicin IV over 1 hour on days 1 and 2. Beginning 28 to 100 days after start of first cycle, patients receive inotuzumab ozogamicin IV over 1 hour on days 1 and 2 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Дати
| Последна проверка: | 06/30/2020 |
| Първо изпратено: | 02/20/2019 |
| Очаквано записване подадено: | 02/24/2019 |
| Първо публикувано: | 02/26/2019 |
| Изпратена последна актуализация: | 07/16/2020 |
| Последна актуализация публикувана: | 07/20/2020 |
| Действителна начална дата на проучването: | 10/27/2019 |
| Приблизителна дата на първично завършване: | 03/30/2021 |
| Очаквана дата на завършване на проучването: | 03/30/2021 |
Състояние или заболяване
Интервенция / лечение
Procedure: Allogeneic Bone Marrow Transplantation
Biological: Anti-Thymocyte Globulin
Drug: Group II (inotuzumab ozogamicin, chemotherapy, transplant)
Biological: Filgrastim-sndz
Drug: Fludarabine
Biological: Inotuzumab Ozogamicin
Drug: Group I (inotuzumab ozogamicin, chemotherapy, transplant)
Drug: Methotrexate
Procedure: Peripheral Blood Stem Cell Transplantation
Biological: Rituximab
Drug: Tacrolimus
Фаза
Групи за ръце
| Arm | Интервенция / лечение |
|---|---|
| Experimental: Group I (inotuzumab ozogamicin, chemotherapy, transplant) See Detailed Description. | Drug: Group I (inotuzumab ozogamicin, chemotherapy, transplant) Given IV |
| Experimental: Group II (inotuzumab ozogamicin, chemotherapy, transplant) See Detailed Description. | Drug: Group II (inotuzumab ozogamicin, chemotherapy, transplant) Given IV |
Критерии за допустимост
| Възрасти, отговарящи на условията за проучване | 18 Years Да се 18 Years |
| Полове, допустими за проучване | All |
| Приема здрави доброволци | Да |
| Критерии | Inclusion Criteria: - Young adults (age 18-35) with ALL will be included only if they are not eligible for myeloablative transplants. - CD22+ lymphoid malignancies including B acute lymphoblastic leukemia (B-ALL). - Eligible to receive a reduced-intensity allogeneic hematopoietic stem cell transplantation (alloSCT). - Donor: HLA compatible related or matched unrelated donor (HLA-A, B, C, DRB1). - Performance status of 0 to 2. - Creatinine less than or equal to 1.6 mg/dL (at time of study entry). - Bilirubin less than 1.6 mg/dL (at time of study entry). - Serum glutamate pyruvate transaminase (SGPT) < 2 x upper limit of normal (ULN) (at time of study entry). - Ejection fraction >= 40% (at time of study entry). - Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) >= 40% (at time of study entry). - Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast-feeding. Pregnancy testing is not required for post menopausal or surgically sterilized women. Exclusion Criteria: - Human immunodeficiency virus (HIV) positive. - Philadelphia chromosome (Ph)-positive ALL. - Active and uncontrolled disease/infection. - Unable or unwilling to sign consent. - Current active hepatic or biliary disease (with exception of Gilbert's syndrome). - Active hepatitis B or C. - Recent chemotherapy or radiation within 3 weeks of study entry. Exception: ibrutinib and venetoclax are allowed to within 3 days. - Prior inotuzumab ozogamicin within 3 weeks of study entry. - Peripheral blast count of greater than 10 K/microL. - Corrected QT using Fridericia's formula (QTcF) interval > 470 ms. |
Резултат
Първични изходни мерки
1. Incidence of grade 3 or higher renal, hepatic, cardiac, pulmonary, or neurologic toxicity [Up to 30 days after cycle 1 of maintenance therapy]
Вторични изходни мерки
1. Treatment-related mortality (TRM) [Up to 2 years]
2. Relapse [Up to 2 years]
3. Overall survival (OS) [Up to 2 years]
4. Progression-free survival (PFS) [Up to 2 years]
5. Acute graft versus host disease (GVHD) [Up to 2 years]
6. Chronic GVHD [Up to 2 years]
