Auto Stem Cell Transplant for Lymphoma Patients

Официальное название

Autologous Stem Cell Transplant In Patients With Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphomas (NHL)

Обзор

This is a phase II study of autologous transplant for patients with Hodgkin (HL) and non-Hodgkin lymphomas (NHL) including those who are HIV positive.

Вмешательства

• Препарат Etoposide
  BEAM: 100 mg/m\^2 IV over 2 hours BID on Days -5, -4, -3, -2 \| CBV: 150 mg/m\^2 intravenously over 4 hours every 12 hours starting at 6 a.m. and 6 p.m. on Days -6, -5, -4
• Препарат BCNU
  BEAM \& CBV: 300 mg/m\^2 IV over over 2 hours on Day -6
• Препарат AraC
  BEAM: 100 mg/m\^2 IV over 1 hour BID on Days -5, -4, -3, -2
• Препарат Melphalan
  BEAM: 140 mg/m\^2 IV over 20 minutes on Day -1
• Процедура Peripheral blood stem cell transplantation
  All Arms: Day 0 infuse PBSC. All patients will have PBSC collected by leukapheresis. Mobilization will be done with G-CSF.
• Биопрепарат G-CSF
  All patients should receive G-CSF, 5 ug/kg/day IV as a bolus injection each evening beginning on day +5 until the ANC is \>2500 x 10\^9/L for 2 consecutive days. G-CSF will subsequently be restarted at 5 ug/kg/day SC or IV if the ANC falls below 1000/mm\^3
• Препарат Cyclophosphamide
  CBV: 1.5 gm/M\^2 over 2 hours at 10 a.m. on Days -6, -5, -4, -3 \| CY/TBI: 60 mg/kg IV over 2 hours on Days -7, -6
• Лучевая терапия Total Body Irradiation
  CY/TBI: 165 cGy bid on Day -4, -3, -2, -1

Первичные конечные точки

• Progression Free Survival Comparison [Срок оценки: 3 years post transplant]

Вторичные конечные точки (6)

• Overall Survival [Срок оценки: 3 years post transplant]
• Treatment related mortality [Срок оценки: 6 months post transplant]
• Treatment related mortality [Срок оценки: 1 year post transplant]
• Secondary malignancies [Срок оценки: 3 years post transplant]
• Neutrophil engraftment [Срок оценки: Day +1 to engraftment]
• Platelet engraftment [Срок оценки: Day +1 to engraftment]

Критерии участия

Критерии включения

• Eligible Diseases

• Non-Hodgkin's Lymphoma (NHL)

• Patients with chemo-sensitive histologically confirmed NHL will be eligible for this treatment protocol contingent on histologic sub-classification.
• Patients in partial or complete remission following cell therapy will also be eligible.
• NHL patients with resistant or refractory lymphoma (no PR following up to three cycles of combination chemotherapy) will not be eligible for transplant in this trial.
• Lymphoblastic Lymphoma:

• All patients will be eligible in second or greater complete remission (CR) or first or subsequent partial remission (PR)
• Patients with any high-risk features will be eligible in first complete remission
• High risk features include: Stage IV, LDH >2 x upper limit of normal, ≥ 2 extranodal sites
• Mature B-cell Lymphoma

• Follicular Lymphoma and other indolent lymphoma in ≥ second CR2/PR2
• Diffuse Large B-Cell Lymphoma: in ≥ CR2 or ≥ PR1; a high intermediate or high IPI (≥ 2 for age-adjusted IPI or ≥3 for IPI) at diagnosis and double-hit or triple-hit lymphoma will be eligible in first CR; transformed lymphoma from FL (or other indolent lymphoma) or chronic lymphocytic leukemia will be eligible if chemosensitive and bone marrow is negative
• Mantle Cell Lymphoma: in first or greater CR or PR
• Burkitt's/Burkitt's like: all patients except localized lymphoma will be eligible any time after initial therapy (after achievement of first complete remission), or in partial remission if they fail to achieve CR; patients with localized (stage I or Ziegler stage A) will be eligible only if they fail to achieve CR1 or after relapse
• Mature T-Cell Lymphoma

• Chemosensitive T-cell lymphomas including Primary T-cell not otherwise specified angioimmunoblastic, and ALK-positive anaplastic large cell, will be eligible after initial therapy, whether or not CR is achieved.
• Mycosis fungoides/Sezary syndrome will be eligible in ≥CR2/PR2
• Hodgkin Lymphoma (HL)

• Patients with histologically proven HL will be eligible for transplantation after failing prior therapy.
• Patients with resistant disease (initial or at relapse): those who fail to achieve an objective partial response to three cycles of combination non-cross resistant chemotherapy will not be eligible for transplant in this trial.
• For stage I/II patients treated with primary chemotherapy-radiation, they must have failed (no CR or progression after CR) at least one salvage combination chemotherapy treatment regimen
• For advanced (stage III/IV) Hodgkin disease, patients must have failed an Adriamycin containing regimen (ABVD) or an alternative non-cross resistant regimen (e.g. MOPP)
• Patients with any high-risk features will also be eligible, including those who:

• fail to achieve complete remission with initial combination chemotherapy
• have bulky disease after initial therapy (chemotherapy or radiation) defined as residual mediastinal mass ≥ 5 cm or other residual mass ≥ 10 cm accompanied by other features of persisting disease (e.g., PET scan positive; high LDH; enlarging on serial x-rays or biopsy positive) will be eligible - if feasible, persistent disease should be proven by biopsy
• Patients should receive chemotherapy to attempt to achieve CR or minimal disease state for all patients pre-transplantation. The use of up to three cycles of non-cross resistant combination chemotherapy is advised.
• Residual areas of limited disease should be considered for radiotherapy after and not prior to transplantation.
• HIV positive patients who are otherwise eligible for this study may be enrolled if they meet the following requirements:

• Are seen in the infectious disease (ID)/HIV clinic prior to enrollment on study for the purpose of determining eligibility and for local coordination of HIV care during the peri-transplant period.
• Are on maximally active anti-HIV regimen to control disease as determined appropriate by the ID/HIV physicians. For the majority of patients, this will be a highly active anti-retroviral therapy (HAART)-type therapy including a protease inhibitor.
• CD4+ ≥ 50/µL
• HIV RNA viral load ≤ 100,000 copies per mL on each of samples 4 weeks apart. The most recent level must be within 30 days of enrollment.
• Performance Status: Karnofsky Performance Status ≥ 80% for patients ≥ 16 years of age or Lansky Play Score ≥ 80 for patients < 16 years of age. Note: if poor performance status is due to lymphoma - KPS ≥ 60% or LPS ≥ 60 is acceptable
• Organ Function

1\. No evidence of serious organ dysfunction that is not attributable to tumor including:

• Hematologic:

• hemoglobin > 8 gm/dL
• WBC > 2.5 x 109/L with an ANC > 1.5 x 109/L off G-CSF or GM-CSF for 10 days or Neulasta for 21 days
• platelets > 100 x 109/L without transfusion
• bone marrow cellularity of > 20% with <5% involvement with tumor
• Renal: GFR > 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x ULN for age
• Hepatic: no history of severe prior or ongoing chronic liver disease. Total bilirubin ≤ 2.0 mg/dl, AST and alkaline phosphatase <5x upper limit of normal
• Cardiac: free of symptoms of uncontrolled cardiac disease including unstable angina, decompensated congestive heart failure, or arrhythmia. The ejection fraction by gated cardiac blood flow scan (MUGA) or Echocardiogram must be >40%
• Pulmonary: no significant obstructive airways disease (FEV1 must be ≥ 50%) and must have acceptable diffusion capacity (corrected DLCO > 50% of predicted)
• Central Nervous System: Patients with a history of CNS involvement by lymphoma or with relapsed primary CNS lymphoma will be eligible for Cy/TBI arm. Patients with active CNS disease are eligible if they have completed a standard treatment for CNS lymphoma and have no evidence of progressive CNS disease at the time of enrollment
• Other Inclusion Criteria

• At least 4 weeks from previous chemotherapy; 6 weeks from nitrosoureas
• Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment
• Patients who are carriers of Hepatitis B will be included in this study
• Voluntary written consent

Критерии исключения

• Pregnant or breastfeeding: Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy
• Eligible for any higher priority transplant protocols
• Chemotherapy resistant disease
• Unrelated active infection

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Masonic Cancer Center, University of Minnesota — Minneapolis

Идентификаторы

NCT: NCT03125642 · 2016LS132 · MT2016-11C

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗