Cyclophosphamide and Alemtuzumab in Treating Patients with Relapsed or Refractory Non-Hodgkin Lymphoma
This phase I trial studies the side effects and best dose of cyclophosphamide and alemtuzumab in treating patients with non-Hodgkin lymphoma that have come back or do not respond to treatment. Drugs used in chemotherapy, such as cyclophosphamide and alemtuzumab, 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.
Inclusion Criteria
- Histologically confirmed non-Hodgkin lymphoma and be considered ineligible for standard curative therapeutic options, including high dose chemotherapy with autologous stem cell rescue
- Falls under one of the following subtypes of CD52 positive non-Hodgkin lymphoma (defined as >= 50% positive staining by immunohistochemical staining or flow cytometry by local lab): * High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements (DHL) * DLBCL or high-grade B-cell lymphoma NOS or B-cell lymphoma unclassifiable with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma with MYC and BCL2 protein over-expression by immunohistochemical (IHC) staining as defined by MYC expression in >= 30% of cells and BCL2 positivity >= 50% (DOL) * Transformed lymphoma with MYC rearrangement by fluorescence in situ hybridization (FISH) or over-expression by IHC, as above * CD52 positive mature T-cell lymphoproliferative disorder
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Leukocytes >= 1,000/mcL
- Absolute neutrophil count >= 500/mcL
- Platelets >= 25,000/mcL
- Total bilirubin =< 2.4 mg/dL unless related to Gilbert’s disease or patient’s lymphoma
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
- Creatinine clearance < 1.5 x institutional ULN
- Ability to understand and the willingness to sign a written informed consent document
- NOTE: There is no limit to the prior number of chemotherapy regimens; patients with prior autologous or allogeneic stem cell transplantation, as well as prior therapy with cyclophosphamide or alemtuzumab, are eligible
Exclusion Criteria
- Chemotherapy or radiotherapy within 1 week (4 weeks for nitroureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Receiving any other investigational agents for their lymphoma
- Received corticosteroids within the past 1 week
- Known active central nervous system (CNS) involvement by lymphoma should be excluded from this clinical trial
- History of allergic reactions attributed to cyclophosphamide or alemtuzumab
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hematuria related to bladder injury or psychiatric illness/social situations that could limit compliance with study requirements
- Positive pregnancy test; Note: Pregnant women are excluded from this study; breastfeeding should be discontinued; negative serum pregnancy test will be required for women of childbearing potential
- Human immunodeficiency virus (HIV)-positive and on combination antiretroviral therapy
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03132584.
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated doses of cyclophosphamide and alemtuzumab in patients with; CD52 positive high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements; (DHL); diffuse large B-cell lymphoma (DLBCL) or high grade B-cell lymphoma not otherwise specified (NOS) with MYC and BCL2 over-expression; transformed lymphoma (TL) with MYC rearrangement or overexpression or CD52 positive mature T-cell lymphoproliferative disorder T-LPD (TLPD).
II. To characterize the toxicity of cyclophosphamide and alemtuzumab administered at the MTD.
SECONDARY OBJECTIVES:
I. To assess the overall and complete response rate of the regimen.
II. To assess progression free and overall survival.
III. To assess response by positron emission tomography (PET)/computed tomography (CT) and in the bone marrow after one cycle of therapy.
TERTIARY OBJECTIVES:
I. To assess changes in bone marrow and/or extramedullary site on day 8 (+/-2 days) of cycle 1 by immunohistochemistry (IHC), transcriptomics, proteomics, and functional assessments.
II. To assess changes in bone marrow and/or extramedullary site/lymph node at time of progression by IHC, transcriptomics, proteomics, and functional assessments.
OUTLINE: This is a dose-escalation study.
Patients receive alemtuzumab intravenously (IV) over 2 hours on days 1-4 and cyclophosphamide IV over 2 hours on day 3. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients will be followed up every 3 months for up to 1 year.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorAnn Steward LaCasce
- Primary ID17-034
- Secondary IDsNCI-2017-01686
- ClinicalTrials.gov IDNCT03132584