Chemotherapy with or without Total Body Irradiation before Stem Cell Transplant in Treating Patients with Hodgkin or Non-Hodgkin Lymphoma

Status: Active

Description

This phase II trial studies how well chemotherapy with or without total body irradiation before stem cell transplantation works in treating patients with Hodgkin or non-Hodgkin lymphoma. Drugs used in chemotherapy, such as carmustine, etoposide, cytarabine, and melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy, such as total body irradiation, uses high energy x-rays to kill cancer cells and shrink tumors. It is not known whether chemotherapy with or without total body irradiation before stem cell transplant works better in treating patients with Hodgkin or non-Hodgkin lymphoma.

Eligibility Criteria

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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

Locations & Contacts

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: Active
Contact: Veronika Bachanova
Phone: 612-625-8942

Trial Objectives and Outline

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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 & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Minnesota / Masonic Cancer Center

Principal Investigator
Veronika Bachanova

Trial IDs

Primary ID 2016LS132
Secondary IDs NCI-2017-01037
Clinicaltrials.gov ID NCT03125642