Phase I Study of Yttrium-90 Labeled Anti-CD25 Monoclonal Antibody Plus Standard BEAM Conditioning for Autologous Hematopoietic Cell Transplantation in Patients With Mature T-Cell Non-Hodgkin Lymphoma: the aTAC BEAM Regimen
Overview
- Phase
- Phase 1
- Intervention
- Yttrium Y 90 Basiliximab
- Conditions
- Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
- Sponsor
- City of Hope Medical Center
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- MTD of yttrium Y 90 basiliximab defined as the highest dose in which fewer than 33% of patients experience dose limiting toxicity attributable to study treatment, among those evaluable for toxicity
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This phase I trial studies the side effects and best dose of yttrium Y 90 basiliximab when given together with standard combination chemotherapy before a stem cell transplant in treating patients with mature T-cell non-Hodgkin lymphoma. Radioactive substances linked to monoclonal antibodies, such as yttrium Y 90 basiliximab, can bind to cancer cells and give off radiation which may help kill cancer cells. Drugs used in chemotherapy, such as carmustine, cytarabine, etoposide, and melphalan (BEAM), 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. Giving yttrium Y 90 basiliximab and chemotherapy before a stem cell transplant may help kill any cancer cells that are in the body and help make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Stem cells that were collected from the patient's blood and stored before treatment are later returned to the patient to replace the blood-forming cells that were destroyed.
Detailed Description
PRIMARY OBJECTIVES: I. To determine if administration of 90Y-basiliximab/DOTA (yttrium Y 90 basiliximab), when given in combination with standard dose BEAM, as conditioning for autologous hematopoietic cell transplant (AHCT), is safe, by evaluation of toxicities, including type, frequency, severity, attribution, time course and duration. II. To determine the maximum tolerated dose (MTD) of 90Y-basiliximab/DOTA when given in combination with standard dose BEAM, in patients with T-cell non-Hodgkin lymphoma (T-NHL) as part of conditioning for AHCT. SECONDARY OBJECTIVES: I. To characterize and evaluate hematologic recovery in terms of neutrophil and platelet engraftment time. II. To estimate radiation doses to the whole body and normal organs through serial imaging studies. III. To estimate overall survival, progression-free survival, non-relapse mortality and cumulative incidence of relapse/progression at 100-days (non-relapse mortality \[NRM\] only), 1-year and 2-years. OUTLINE: This is a dose-escalation study of yttrium Y 90 basiliximab. Patients receive yttrium Y 90 basiliximab intravenously (IV) on days -21 and -14, carmustine IV over 1-2 hours on days -7 and -6, cytarabine IV twice daily (BID) on days -5 to -2, etoposide IV BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic stem cell transplant on day 0. After completion of study treatment, patients are followed up at 30, 100, and 180 days and 1, 1.5, and 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with a pathologically confirmed diagnosis of systemic mature T-cell non-Hodgkin lymphoma (NHL) with City of Hope pathology review as per World Health Organization (WHO) classification of lymphomas 2008, who are deemed eligible for high dose therapy and AHCT including patients in:
- •\* T-NHL histologies including peripheral T-cell lymphomas (PTCLs), cutaneous T-cell lymphomas (CTCLs) and natural killer (NK)/T cell lymphomas
- •First remission after initial first-line therapy (CR1) in PTCL patients, except for anaplastic lymphoma receptor tyrosine kinase (ALK)+ anaplastic large cell lymphoma (ALCL) and CTCL; patients with minimal residual disease after induction therapy may also be eligible at the discretion of the principal investigator (PI)
- •Relapsed/refractory disease, stable disease, partial remission (PR) or complete remission (CR), who have received at least 2 lines of therapy, and do not have an adequate allogenetic stem cell transplant option
- •Life expectancy \>= 6 months
- •Karnofsky status \>= 70%
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
- •Cardiac ejection fraction of \>= 50% by echocardiogram or multi gated acquisition scan (MUGA)
- •Forced expiratory volume in one second (FEV1) \> 65% of predicted measured, or diffusing capacity of the lung for carbon monoxide (DLCO) \> 50% of predicted measured
- •Bilirubin \< 1.5 x normal except in cases where abnormal liver function tests (LFTS) are due to involvement with T-NHL
Exclusion Criteria
- •Progressive disease
- •Patients should not have any uncontrolled illness including ongoing or active infection requiring therapy
- •Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy; may have received an experimental agent prior to enrolling in the trial
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to basiliximab
- •Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with indium In 111 (111In-) and 90Y-basiliximab-DOTA
- •Prior high dose chemotherapy for autologous hematopoietic cell transplantation or prior allogeneic transplantation
- •Significant prior external beam dose-limiting radiation to a critical organ based on review of the prior radiation treatment records by the Radiation Oncology PI; patients who have had prior external beam radiation \> 2000 cGy (at 180 to 200 cGy per day) to the lung will be ineligible; patients with ANY prior radiation to the heart are ineligible; patients with \> 500 cGy to the kidney will be excluded from the study; Note: patients who have had electron beam therapy are still eligible and will be evaluated on a case by case basis by the Radiation Oncology PI
- •Presence of antibody against basiliximab in serum (only required for patients who have received prior antibody)
- •Research participants with presence of other active malignancy; however, research participants with history of prior malignancy treated with curative intent and in complete remission are eligible; any history of myelodysplasia is excluded
- •Active hepatitis B or C viral infection or hepatitis B surface antigen positive
Arms & Interventions
Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)
Patients receive yttrium Y 90 basiliximab IV on days -21 and -14, carmustine IV over 1-2 hours on days -7 and -6, cytarabine IV BID on days -5 to -2, etoposide IV BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic stem cell transplant on day 0.
Intervention: Yttrium Y 90 Basiliximab
Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)
Patients receive yttrium Y 90 basiliximab IV on days -21 and -14, carmustine IV over 1-2 hours on days -7 and -6, cytarabine IV BID on days -5 to -2, etoposide IV BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic stem cell transplant on day 0.
Intervention: Carmustine
Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)
Patients receive yttrium Y 90 basiliximab IV on days -21 and -14, carmustine IV over 1-2 hours on days -7 and -6, cytarabine IV BID on days -5 to -2, etoposide IV BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic stem cell transplant on day 0.
Intervention: Etoposide
Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)
Patients receive yttrium Y 90 basiliximab IV on days -21 and -14, carmustine IV over 1-2 hours on days -7 and -6, cytarabine IV BID on days -5 to -2, etoposide IV BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic stem cell transplant on day 0.
Intervention: Cytarabine
Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)
Patients receive yttrium Y 90 basiliximab IV on days -21 and -14, carmustine IV over 1-2 hours on days -7 and -6, cytarabine IV BID on days -5 to -2, etoposide IV BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic stem cell transplant on day 0.
Intervention: Melphalan
Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)
Patients receive yttrium Y 90 basiliximab IV on days -21 and -14, carmustine IV over 1-2 hours on days -7 and -6, cytarabine IV BID on days -5 to -2, etoposide IV BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic stem cell transplant on day 0.
Intervention: Autologous Hematopoietic Stem Cell Transplantation
Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)
Patients receive yttrium Y 90 basiliximab IV on days -21 and -14, carmustine IV over 1-2 hours on days -7 and -6, cytarabine IV BID on days -5 to -2, etoposide IV BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic stem cell transplant on day 0.
Intervention: Laboratory Biomarker Analysis
Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)
Patients receive yttrium Y 90 basiliximab IV on days -21 and -14, carmustine IV over 1-2 hours on days -7 and -6, cytarabine IV BID on days -5 to -2, etoposide IV BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic stem cell transplant on day 0.
Intervention: Pharmacological Study
Outcomes
Primary Outcomes
MTD of yttrium Y 90 basiliximab defined as the highest dose in which fewer than 33% of patients experience dose limiting toxicity attributable to study treatment, among those evaluable for toxicity
Time Frame: 30 days post-transplant
Dose limiting toxicities will be graded by the Modified Bearman scale.
Incidence of toxicities assessed using National Cancer Institute (NCI) CTCAE version 4.03
Time Frame: Up to 100 days post-transplant
Observed toxicities will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.03 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.
Secondary Outcomes
- Disease response by Cheson 2007 criteria(Up to 2 years post-transplant)
- Engraftment: neutrophil and platelet recovery(Up to 2 years post-transplant)
- Overall survival(From start of therapy (stem cell infusion) to death from any cause, assessed up to 2 years post-transplant)
- Progression-free survival(From start of therapy (stem cell infusion) to the first observation of disease relapse/progression or death from any cause, assessed up to 2 years post-transplant)
- Non-relapse mortality(From start of therapy until non-disease related death, or last follow-up, whichever comes first, assessed up to 2 years post-transplant)
- Cumulative incidence of relapse/progression(From start of therapy (stem cell infusion) to the first observation of disease relapse/progression, assessed up to 2 years post-transplant)
- Absorbed radiation dose to organs assessed by nuclear scan images(Up to day -14)