Radiolabeled Monoclonal Antibody Therapy and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With Primary Refractory or Relapsed Hodgkin Lymphoma
This phase I/II clinical trial studies the side effects and best dose of radiolabeled monoclonal antibody therapy when given together with combination chemotherapy before stem cell transplant and to see how well it works in treating patients with primary refractory or relapsed Hodgkin lymphoma. Radiolabeled monoclonal antibodies can find cancer cells and carry cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as carmustine, etoposide, cytarabine, and melphalan (BEAM), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving radiolabeled monoclonal antibody therapy together with combination chemotherapy may kill more cancer cells
Recurrent Adult Hodgkin Lymphoma
Other: pharmacological study
Other: laboratory biomarker analysis
Procedure: autologous hematopoietic stem cell transplantation
Biological: yttrium Y 90-labeled basiliximab
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Yttrium-90 Labeled Anti-CD25 (a-Tac) Monoclonal Antibody Plus BEAM for Autologous Hematopoietic Cell Transplantation (AHCT) in Patients With Primary Refractory or Relapsed Hodgkin Lymphoma, the "a-Tac BEAM Regimen"|
- RP2D of Yttrium-90 labeled basiliximab (phase I) [ Time Frame: Up to 18 months ] [ Designated as safety issue: Yes ]RP2D is defined as the highest Yttrium-90 labeled basiliximab dose tested in which fewer than 33% of patients experience dose limiting toxicity (DLT) attributable to study treatment, among those evaluable for toxicity. Additional pulmonary toxicity monitoring will be performed among enrolled/treated patients with prior brentuximab vedotin exposure for both portions of the study.
- DLT (phase I) [ Time Frame: For 30 days post-transplant ] [ Designated as safety issue: Yes ]Toxicities will be recorded using two distinct grading systems: the modified Bearman Scale and the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCASE) 4.0 scale. Observed toxicities will be summarized by type, severity, date of onset, duration, reversibility, and attribution.
- Anti-tumor activity of the regimen, as assessed by PFS (phase II) [ Time Frame: Time from transplant to the first observation of disease progression or death from any cause, whichever occurs first, assessed at 2 years ] [ Designated as safety issue: No ]Progression Free Survival (PFS) will be estimated using the Kaplan-Meier (KM) product-limit method. 95% confidence intervals (CIs) will be calculated using the logit transformation and the Greenwood variance estimate. Estimated from radiolabeled therapeutic infusion and from stem cell infusion.
- ORR (phase I) [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]Response will be evaluated using the revised Cheson criteria. Objective tumor response for all patients will be summarized for each dose level, and the number and percent responding combined across dose levels.
- Biodistribution/analyses of basiliximab (phase I) [ Time Frame: Pre-basiliximab infusion; pre radiolabeled basiliximab infusion; 2 and 4-6 hours post radiolabeled basiliximab infusion; and then 1, 2, 3-4, 5, and 6 days post radiolabeled basiliximab ] [ Designated as safety issue: No ]Serum basiliximab levels will be evaluated. T1/2 and alpha- and beta- phase will be estimated for each patient using compartmental and non-compartmental methods, with summary statistics tabulated. Exploratory models to predict tumor response, survival, and toxicities from serum data and patient characteristics will be performed to better understand the effect of treatment on patients.
- Overall survival (phase II) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Estimated using the KM product-limit method; 95% CIs will be calculated using the logit transformation and the Greenwood variance estimate. Estimated using two different start times (from radiolabeled therapeutic infusion and from stem cell infusion) to death from any cause.
- ORR: CR + PR (phase II) [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]Evaluated using the Cheson Revised Response Criteria for Malignant Lymphoma.
- Response duration (phase II) [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]Defined as time from when criteria for response (CR or PR) are met, for which the event is the first documentation of relapse or progression.
- Toxicities and complications (phase I and II) [ Time Frame: Up to 100 days post-infusion ] [ Designated as safety issue: Yes ]For both the phase I and phase II studies, observed toxicities will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE v4.0 and nadir or maximum values for lab measures), dated of onset, duration, reversibility, and attribution.
|Study Start Date:||November 2012|
|Estimated Primary Completion Date:||January 2021 (Final data collection date for primary outcome measure)|
Experimental: Treatment (radiolabeled monoclonal antibody, chemotherapy)
DOSIMETRY STUDY: Patients receive basiliximab IV and indium In 111 basiliximab IV on day -21. Patients undergo indium In 111 imaging scans daily. Patients with appropriate biodistribution continue on to treatment.
TREATMENT: Patients receive basiliximab IV and yttrium Y 90 basiliximab IV on day -14. Patients also receive BEAM chemotherapy comprising carmustine IV over 2 hours on days -7 and -6, etoposide IV BID over 4 hours and cytarabine IV over 2 hours BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic progenitor cell infusion on day 0.
Other Names:Drug: carmustine
Other Names:Drug: etoposide
Other Names:Drug: cytarabine
Other Names:Drug: melphalan
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
Correlative studiesProcedure: autologous hematopoietic stem cell transplantation
Undergo autologous hematopoietic progenitor cell infusionBiological: yttrium Y 90-labeled basiliximab
Other Name: 90Y basiliximab
I. To determine the safety and feasibility of the autologous hematopoietic cell transplantation (AHCT) regimen of Yttrium Y-90 basiliximab/DOTA, given in combination with standard dose(s) of BEAM in patients with primary progressive or relapsed Hodgkin lymphoma (HL).
(Phase I) II. To determine the recommended phase II dose (RP2D) and characterize toxicities at each dose level -including time course.
(Phase I) III. To evaluate hematological recovery in terms of neutrophil and platelet engraftment time.
(Phase I) IV. To estimate the radiation doses to the whole body and normal organs through serial imaging studies.
(Phase I) V. To define biodistribution/extended pharmacokinetics of 111Indium (In)-basiliximab/DOTA and 90Y- basiliximab/DOTA including terminal elimination, serum half-life (t1/2), and area under the curve (AUC).
(Phase I) VI. Using the RP2D defined in the Phase I study, to determine anti-tumor activity of anti (a)Tac-BEAM as assessed by progression-free survival (PFS).
(Phase II) VII. To determine the overall response rate (ORR: complete remission [CR] + partial remission [PR]) and response duration.
(Phase II) VIII. To estimate the overall survival, and non-relapse mortality (NRM) at 100-days and 1-year.
(Phase II) IX. To summarize toxicities by organ and severity, evaluating short and long-term complications, including, delayed engraftment, infection, and myelodysplasia.
(Phase II) X. To descriptively compare the outcomes of patients treated on this protocol to a comparable patient population treated with conventional BEAM for relapsed and refractory HL.
(Phase II) OUTLINE: DOSIMETRY STUDY: Patients receive basiliximab intravenously (IV) and indium In 111 basiliximab IV on day -21. Patients undergo indium In 111 imaging scans daily. Patients with appropriate biodistribution continue on to treatment.
TREATMENT: Patients receive basiliximab IV and yttrium Y 90 basiliximab IV on day -14. Patients also receive BEAM chemotherapy comprising carmustine IV over 2 hours on days -7 and -6, etoposide IV over 4 hours twice daily (BID) and cytarabine IV over 2 hours BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic progenitor cell infusion on day 0.
After completion of study treatment, patients are followed up at day 90-100, 180, 1 year, 1.5 years, and 2-5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01476839
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Eileen P. Smith 800-826-4673 email@example.com|
|Principal Investigator: Eileen P. Smith|
|Principal Investigator:||Eileen Smith||City of Hope Medical Center|