Chemotherapy with or without Total Body Irradiation before Stem Cell Transplant in Treating Patients with Hodgkin or Non-Hodgkin Lymphoma
- 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 partial remission [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 ** Lactate dehydrogenase (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 international prognostic index (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 follicular lymphoma (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
- Patients with histologically proven Hodgkin lymphoma (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 (adriamycin-bleomycin-vinblastine-dacarbazine [ABVD]) or an alternative non-cross resistant regimen (e.g. mustargen-oncovin-procarbazine-prednisone [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., positron emission tomography [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 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
- Human immunodeficiency virus (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/uL * HIV ribonucleic acid (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
- 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 - Karnofsky performance status (KPS) >= 60% or Lansky performance score (LPS) >= 60 is acceptable
- Hemoglobin > 8 gm/dL
- White blood cell (WBC) > 2.5 x 10^9/L with an absolute neutrophil count (ANC) > 1.5 x 10^9/L off granulocyte colony-stimulating factor (G-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF) for 10 days or Neulasta for 21 days
- Platelets > 100 x 10^9/L without transfusion
- Bone marrow cellularity of > 20% with < 5% involvement with tumor
- Glomerular filtration rate (GFR) > 50 ml/min/1.73 m^2 or serum creatinine =< 2.5 x upper limit of normal (ULN) for age
- No history of severe prior or ongoing chronic liver disease
- Total bilirubin =< 2.0 mg/dl
- Aspartate aminotransferase (AST) < 5 x upper limit of normal
- Alkaline phosphatase < 5 x upper limit of normal
- 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%
- No significant obstructive airways disease (forced expiratory volume in 1 second [FEV1] must be >= 50%) and must have acceptable diffusion capacity (corrected carbon monoxide diffusing capability [DLCO] > 50% of predicted)
- Patients with a history of central nervous system (CNS) involvement by lymphoma or with relapsed primary CNS lymphoma will be eligible for cyclophosphamide (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
- 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
- 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
- Untreated active infection
I. To estimate overall survival (OS) at 3 years post-transplant for patients who received the radiation free preparative regimen carmustine, etoposide, cytarabine, and melphalan (BEAM).
I. Progression free survival (PFS) at 3 years post-transplant.
II. Treatment related mortality (TRM) at 6 months and 1 year.
III. Cumulative incidence of secondary malignancies in 3 years post-transplant.
IV. Time to neutrophil and platelet engraftment.
V. Compare the primary and secondary endpoints between patients who received the radiation free preparative regimen BEAM to the prior study MT2004-24 where non-Hodgkin lymphoma (NHL) subjects received total body irradiation (TBI) as part of their preparative regimen.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I: Patients receive carmustine intravenously (IV) over 2 hours on day -6, etoposide IV over 2 hours twice daily (BID) on days -5 to -2, cytarabine IV over 1 hour BID on days -5 to -2, and melphalan IV over 20 minutes on day -1. Patients undergo autologous hematopoietic stem cell transplantation (HSCT) on day 0. Patients receive granulocyte colony-stimulating factor (G-CSF) IV or subcutaneously (SC) starting on day 5.
ARM II: Patients receive cyclophosphamide IV over 2 hours on days -7 and -6. Patients undergo total body irradiation (TBI) BID on days -4 to -1 and HSCT on day 0. Patients receive G-CSF IV or SC starting on day 5.
After completion of study treatment, patients are followed up to 3 years.
Trial Phase Phase II
Trial Type Treatment
University of Minnesota / Masonic Cancer Center
- Primary ID 2016LS132
- Secondary IDs NCI-2017-01037
- Clinicaltrials.gov ID NCT03125642