Yttrium-90-labeled Daclizumab With Chemotherapy and Stem Cell Transplant for Hodgkin s Lymphoma
- Hodgkins lymphoma (HL) is a highly treatable cancer. However, if HL does not respond to chemotherapy or returns after chemotherapy, further treatments often are not successful.
- Some HL cells have a molecule called cluster of differentiation 25 (CD25) on the surface. Daclizumab is a drug that can detect CD25 on cells. In a treatment study for HL that did not respond to chemotherapy, daclizumab plus a radioactive atom called Yttrium 90 helped kill these HL cells. Researchers want to combine this 90Y daclizumab with high-dose chemotherapy and stem cell transplant. This treatment may be more effective than the daclizumab alone.
- To see if yttrium-90 daclizumab, high-dose chemotherapy, and stem cell transplants can treat HL that has not responded to earlier treatments.
- Individuals at least 18 years of age who have Hodgkins lymphoma that has not responded to chemotherapy.
- Participants will be screened with a physical exam and medical history. They will also have blood and urine tests.
- Participants will have filgrastim and plerixafor to move stem cells into the blood. Stem cells will be collected with apheresis.
- Four weeks after stem cells are collected, participants will have the 90Y daclizumab and normal daclizumab to treat the HL. Chemotherapy will start 9 days after the first treatment.
- Most participants will have a second dose of 90Y daclizumab 6 weeks after the first dose.
- After each daclizumab treatment, participants will have several imaging studies of the chest and abdomen. Blood samples will also be collected.
- On the day after the last day of chemotherapy, participants will receive the stem cells collected earlier. Filgrastim injections will help stimulate stem cell growth....
Procedure: Auto stem cell transplant
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Phase I/II Trial of Yttrium-90-labeled Daclizumab (Anti-CD25) Radioimmunotherapy With High-dose BEAM Chemotherapy and Autologous Hematopoietic Stem Cell Rescue in Recurrent and Refractory Hodgkin s Lymphoma|
- Maximum Tolerated Dose (MTD) of 90Y-daclizumab With Carmustine, Etoposide, Cytarabine, [Ara-C, Cytosine Arabinoside] and Melphalan (BEAM) and Auto Stem Cell Transplant (ASCT): Phase I Portion [ Time Frame: Day 100 post autologous stem cell transplant ]The MTD is defined as the dose level below the dose at which 2 out of 2 to 6 patients at a given dose level develop dose limiting toxicity (DLT). A DLT is defined as patients who develop either a Common Terminology Criteria in Adverse Events (CTCAE) v4.0 grade 3 or greater non-hematologic toxicity, with the exception of fatigue, of more than 5 days duration possibly, probably or definitely related to the infusion of 90Y-daclizumab prior to the start of BEAM chemotherapy (Day - 6) will have developed by definition a dose-limiting toxicity (DLT).
- Number of Participants With Adverse Events [ Time Frame: 30 months ]Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
- Number of Participants With A Dose Limiting Toxicity [ Time Frame: 30 months ]Patients who develop either a Common Terminology Criteria in Adverse Events (CTCAE) v4.0 grade 3 or greater non-hematologic toxicity, with the exception of fatigue, of more than 5 days duration possibly, probably or definitely related to the infusion of 90Y-daclizumab prior to the start of Carmustine, Etoposide, Cytarabine, [Ara-C, Cytosine Arabinoside] and Melphalan (BEAM) chemotherapy (Day - 6) will have developed by definition a dose-limiting toxicity (DLT).
- Overall Response Rate [ Time Frame: Response is evaluated at day 100 post autologous stem cell transplant, then 1-4 times yearly for 5 years ]Overall response rate is defined as the number of complete and partial responses in patients with refractory or relapsed Hodgkin's disease. Response is assessed by the Revised Response Criteria for Malignant Lymphoma. Complete response requires all of the following: complete disappearance of all detectable clinical evidence of disease and disease related symptoms if present before therapy. A post treatment residual mass is permitted as long as it is positron emission tomography negative. Partial response requires all of the following: at least a 50% reduction in the sum of the product of the diameters of up to 6 of the largest dominant nodes or nodal masses. These nodes or masses should be selected according to all of the following: they should be clearly measurable in at least two perpendicular dimensions; if possible they should be from disparate regions of the body; and they should include mediastinal and retroperitoneal areas of disease whenever these sites are involved.
- Complete Response Rate [ Time Frame: 20 months post autologous stem cell transplant ]Complete response rate is defined as the time it takes a participant to achieve a complete response. Response is assessed by the Revised Response Criteria for Malignant Lymphoma. Complete response requires all of the following: complete disappearance of all detectable clinical evidence of disease and disease related symptoms if present before therapy. A post treatment residual mass is permitted as long as it is positron emission tomography (PET) negative. If a pretreatment PET scan was negative, all lymph nodes and nodal masses must have regressed on computed tomography (CT) to normal size (<1.5 cm in their greatest transverse diameter for nodes >1.5 cm before therapy); Previously involved nodes that were 1.1 to 1.5 cm in their long axis and more than 1.0 cm in their short axis before treatment must have decreased to <1.0 cm in their short axis after treatment.
- Disease Free Survival (DFS) [ Time Frame: DFS is evaluated at day 100 post autologous stem cell transplant, then 1-4 times yearly for 5 years ]DFS is defined as the amount of time participants remain disease free.
- Overall Survival [ Time Frame: OS is evaluated at day 100 post autologous stem cell transplant, then 1-4 times yearly for 5 years ]Overall survival is defined as the time from the date of registration to the date of death due to any cause or if no death occurs to the last documented information on the patient.
|Actual Study Start Date:||October 11, 2011|
|Estimated Study Completion Date:||September 1, 2021|
|Primary Completion Date:||November 16, 2014 (Final data collection date for primary outcome measure)|
Experimental: Yttrium-90-labeled Daclizumab + Chemotherapy
Yttrium-90-labeled Daclizumab + BCNU, etoposide, cytarabine and melphalan (BEAM) + Auto stem cell transplant (ASCT)
Procedure: Auto stem cell transplant
Auto stem cell transplant (ASCT) is given after 90Y-daclizumabDrug: BEAM
BCNU, etoposide, cytarabine and melphalan (BEAM) chemotherapy are given after 90Y-daclizumabRadiation: 111In-daclizumab
111In-daclizumab will be administered to patients with each therapeutic infusion of 90Y-daclizumab in order to define the distribution of radiolabeled daclizumab, and to allow visualization by scans.Radiation: 90Y-daclizumab
90Y-daclizumab administered with a fixed dose of pentetate calcium trisodium (Ca-DTPA) followed by BEAM Chemo and Auto stem cell transplant
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01468311
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Thomas A Waldmann, M.D.||National Cancer Institute (NCI)|