Yttrium-90 Labeled Anti-CD25 Monoclonal Antibody Combined With BEAM Chemotherapy Conditioning for the Treatment of Primary Refractory or Relapsed Hodgkin Lymphoma
- Conditions
- Recurrent Hodgkin LymphomaRefractory Hodgkin Lymphoma
- Interventions
- Biological: BasiliximabBiological: Genetically Engineered Hematopoietic Stem Progenitor CellsBiological: Recombinant Granulocyte Colony-Stimulating FactorBiological: Yttrium Y 90 Basiliximab
- Registration Number
- NCT04871607
- Lead Sponsor
- City of Hope Medical Center
- Brief Summary
This phase II trials studies the effects of yttrium-90 labeled anti-CD25 monoclonal antibody combined with BEAM chemotherapy conditioning in treating patients with Hodgkin lymphoma that does not response to treatment (refractory) or has come back (relapsed). Yttrium-90-labeled anti-CD25 is an antibody (proteins made by the immune system to fight infections) that is attached to a radioactive substance and may kill cancer cells and shrink tumors. Chemotherapy drugs, such as carmustine, etoposide, cytarabine, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a peripheral blood stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow.
- Detailed Description
PRIMARY OBJECTIVE:
I. Evaluate the anti-lymphoma activity of the aTac-carmustine (BCNU), etoposide, cytarabine (cytosine arabinoside), and melphalan (BEAM) regimen as conditioning for autologous hematopoietic cell transplantation (AHCT); assessed by 2-year progression-free survival (PFS).
SECONDARY OBJECTIVES:
I. Estimate the overall survival (OS) probability and cumulative incidence of relapse/progression, and non-relapse mortality (NRM) at 100-days, 1-year and 2-years.
II. Summarize toxicities by type, frequency, severity, attribution, time course and duration.
III. Evaluate short and long-term complications, including: delayed engraftment (neutrophil and platelet), infection, and myelodysplasia (MDS).
EXPLORATORY OBJECTIVES:
I. Evaluate potential changes in Hodgkin lymphoma biological markers of patients treated with 90Y basiliximab BEAM via analyses of serial blood samples.
II. Assess the potential association between pre-AHCT CD25 expression levels and post-AHCT outcomes.
OUTLINE:
Patients receive 'cold' basiliximab intravenously (IV) followed by yttrium Y 90 basiliximab IV on day -14. Patients also receive carmustine IV on over 4 hours day -6, etoposide IV over 1 hours once daily (QD) and cytarabine IV over 2 hours twice daily (BID) or QD on days -5 to -2, and melphalan IV over 1 hours on day -1. Patients then receive hematopoietic progenitor cell apheresis (HPC-A) product via infusion on day 0. Beginning day 5, patients receive granulocyte colony-stimulating factor (G-CSF) (or biosimilar) subcutaneously (SC) or IV until absolute neutrophil count (ANC) \> 500 for 3 consecutive days or according to the treating physician's best clinical judgement.
After completion of study treatment, patients are followed up at 30 days, up to 2 years for response, and up to 5 years for survival.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 33
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A) Basiliximab Patients receive 'cold' basiliximab IV followed by yttrium Y 90 basiliximab IV on day -14. Patients also receive carmustine IV on over 4 hours day -6, etoposide IV over 1 hours QD and cytarabine IV over 2 hours BID or QD on days -5 to -2, and melphalan IV over 1 hours on day -1. Patients then receive HPC-A product via infusion on day 0. Beginning day 5, patients receive G-CSF (or biosimilar) SC or IV until ANC \> 500 for 3 consecutive days or according to the treating physician's best clinical judgement. Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A) Genetically Engineered Hematopoietic Stem Progenitor Cells Patients receive 'cold' basiliximab IV followed by yttrium Y 90 basiliximab IV on day -14. Patients also receive carmustine IV on over 4 hours day -6, etoposide IV over 1 hours QD and cytarabine IV over 2 hours BID or QD on days -5 to -2, and melphalan IV over 1 hours on day -1. Patients then receive HPC-A product via infusion on day 0. Beginning day 5, patients receive G-CSF (or biosimilar) SC or IV until ANC \> 500 for 3 consecutive days or according to the treating physician's best clinical judgement. Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A) Recombinant Granulocyte Colony-Stimulating Factor Patients receive 'cold' basiliximab IV followed by yttrium Y 90 basiliximab IV on day -14. Patients also receive carmustine IV on over 4 hours day -6, etoposide IV over 1 hours QD and cytarabine IV over 2 hours BID or QD on days -5 to -2, and melphalan IV over 1 hours on day -1. Patients then receive HPC-A product via infusion on day 0. Beginning day 5, patients receive G-CSF (or biosimilar) SC or IV until ANC \> 500 for 3 consecutive days or according to the treating physician's best clinical judgement. Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A) Yttrium Y 90 Basiliximab Patients receive 'cold' basiliximab IV followed by yttrium Y 90 basiliximab IV on day -14. Patients also receive carmustine IV on over 4 hours day -6, etoposide IV over 1 hours QD and cytarabine IV over 2 hours BID or QD on days -5 to -2, and melphalan IV over 1 hours on day -1. Patients then receive HPC-A product via infusion on day 0. Beginning day 5, patients receive G-CSF (or biosimilar) SC or IV until ANC \> 500 for 3 consecutive days or according to the treating physician's best clinical judgement. Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A) Carmustine Patients receive 'cold' basiliximab IV followed by yttrium Y 90 basiliximab IV on day -14. Patients also receive carmustine IV on over 4 hours day -6, etoposide IV over 1 hours QD and cytarabine IV over 2 hours BID or QD on days -5 to -2, and melphalan IV over 1 hours on day -1. Patients then receive HPC-A product via infusion on day 0. Beginning day 5, patients receive G-CSF (or biosimilar) SC or IV until ANC \> 500 for 3 consecutive days or according to the treating physician's best clinical judgement. Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A) Cytarabine Patients receive 'cold' basiliximab IV followed by yttrium Y 90 basiliximab IV on day -14. Patients also receive carmustine IV on over 4 hours day -6, etoposide IV over 1 hours QD and cytarabine IV over 2 hours BID or QD on days -5 to -2, and melphalan IV over 1 hours on day -1. Patients then receive HPC-A product via infusion on day 0. Beginning day 5, patients receive G-CSF (or biosimilar) SC or IV until ANC \> 500 for 3 consecutive days or according to the treating physician's best clinical judgement. Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A) Etoposide Patients receive 'cold' basiliximab IV followed by yttrium Y 90 basiliximab IV on day -14. Patients also receive carmustine IV on over 4 hours day -6, etoposide IV over 1 hours QD and cytarabine IV over 2 hours BID or QD on days -5 to -2, and melphalan IV over 1 hours on day -1. Patients then receive HPC-A product via infusion on day 0. Beginning day 5, patients receive G-CSF (or biosimilar) SC or IV until ANC \> 500 for 3 consecutive days or according to the treating physician's best clinical judgement.
- Primary Outcome Measures
Name Time Method Progression free survival From the start of treatment up to 5 years post transplant Disease relapse or progression, or death from any cause, whichever occurs first.
Will be calculated using the Kaplan-Meier method.
- Secondary Outcome Measures
Name Time Method Overall survival From the start of treatment up to 5 years post transplant Death from any cause. Will be calculated using the Kaplan-Meier method.
Relapse or progression From the start of treatment up to 5 years post transplant Relapse or progression of Hodgkin lymphoma.
Non-relapse mortality From the start of treatment up to 5 years post transplant Death from causes other than relapse or progression.
Incidence of toxicities and adverse events Day -14 to day 100 post-transplant Toxicity information recorded will include the type, severity, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity. Toxicities will be recorded using both the Bearman criteria and the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 scale.
Time to hematopoietic recovery Up to day 100 post transplant Time to neutrophil recovery will be the first of three consecutive days of ≥ 500 neutrophils/μL following the expected nadir. Time to platelet engraftment will be the first day of the first of three consecutive daily laboratory values when the platelet count is ≥20,000/μL, without a platelet transfusion in the previous seven days.
Incidence of infection Day -14 to day 100 post-transplant Microbiologically documented infections will be reported by site of disease, date of onset, severity and resolution, if any.
Rate of secondary myelodysplastic syndrome From the start of treatment up to 5 years post transplant Secondary MDS or AML post therapy
Trial Locations
- Locations (1)
City of Hope Medical Center
🇺🇸Duarte, California, United States