Yttrium-90-labeled Daclizumab With Chemotherapy and Stem Cell Transplant for Hodgkin's Lymphoma

Hodgkin Lymphoma Clinical Trial

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

Status Terminated

Clinical Trial Summary

Background:

• 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.

Objectives:

• To see if yttrium-90 daclizumab, high-dose chemotherapy, and stem cell transplants can treat HL that has not responded to earlier treatments.

Eligibility:

• Individuals at least 18 years of age who have Hodgkins lymphoma that has not responded to chemotherapy.

Design:

• 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....

Clinical Trial Description

Background:

• Although Hodgkins lymphoma (HL) is considered a highly treatable cancer, patients with relapsed and chemotherapy refractory disease represent a major therapeutic challenge.

• Only 30-65% of relapsed patients will achieve long-term disease free survival with the current standard of care high-dose chemotherapy with autologous hematopoietic stem cell transplant (ASCT).

• The malignant Reed-Sternberg cells of HL and the surrounding benign T cell infiltrates often express CD25, the high affinity interleukin-2 receptor (IL-2R alpha).

• In study NCI-97-C-0110, we treated 30 patients with CD25-expressing relapsed or refractory HL with radioimmunotherapy (RIT) using (90)Y-labeled daclizumab (anti-CD25), and achieved a 63% response rate including 12 complete responses with few serious adverse events other than MDS in 4 patients.

• We propose integrating (90)Y-labeled daclizumab RIT into the induction regimen of ASCT in an effort to improve the response and disease-free survival in relapsed and refractory HL.

Objectives:

Phase I Primary Objectives:

• To assess the safety and adverse events associated with (90)Y-daclizumab (humanized anti-CD25) radioimmunotherapy (RIT) in combination with high-dose BEAM (carmustine, etoposide, cytarabine, [Ara-C, cytosine arabinoside] and melphalan) chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin s lymphoma (HL) with adverse prognostic factors.

• To determine the maximum tolerated dose in mCi of (90)Y-daclizumab RIT in combination with high-dose BEAM chemotherapy and ASCT in patients with relapsed or refractory HL.

Phase II Primary Objectives:

• To assess the frequency of the failure to engraft, myelodysplastic syndrome (MDS), secondary leukemia for the development of abnormal bone-marrow cytogenetics in refractory or relapsed HL patients treated with (90)Y-daclizumab RIT in combination with high-dose BEAM chemotherapy and ASCT.

• To estimate the response rate (the number of complete and partial responses) in patients with refractory or relapsed HD to (90)Y-daclizumab RIT administered in combination with high-dose BEAM chemotherapy and ASCT.

Eligibility:

• Patients must have a confirmed diagnosis of relapsed or refractory HL with at least 10% of malignant Reed-Sternberg cells or infiltrating T-cells expressing CD25 (IL-2R alpha). A. Patients must have at least one of the following: (1) had an initial relapse less than 12 months after achieving a complete response (CR) with primary chemotherapy for HL; (2) were Staged at III/IV at diagnosis; (3) exhibited chemotherapy resistant disease or (4) did not achieve a CR with cytoreductive chemotherapy prior to a planned transplant. B. Patient must have a lesion of at least 1.0 cm in its greatest diameter. C. Patients with lymphocyte predominant HL are excluded. D. Patients with pre-existing myelodysplastic syndrome (MDS) or marrow cytogenic abnormalities will not be eligible to participate.

• Omission of cytotoxic chemotherapy or other systemic therapy of HL for at least 4 weeks prior to entry into the trial.

• No prior ASCT or allogeneic stem cell transplant.

Design:

• A single institution non-randomized open-label phase I/II trial.

• Patients will undergo peripheral blood stem cell (PBSC) mobilization with granulocyte-colony stimulating factor (G-CSF, filgrastim) and Plerixafor followed by apheresis to collect a target dose of 4 x 106 cluster of differentiation 34 (CD34) cells/kg (minimal dose of 2 x 106 CD34+ cells/kg) of actual body weight.

• Phase I study will be carried out using a standard 3 + 3 cohort dose-escalation design:

• Dose level 1: Patients will receive a single dose of 15 mCi 90Y-daclizumab RIT (day -15 2 days) followed by high-dose BEAM chemotherapy (beginning Day -6) and ASCT (Day 0).

• Dose levels 2-7: Patients will receive two doses of 90Y-daclizumab RIT 6 weeks apart (Day -56 and -15 2 days) followed by high-dose BEAM chemotherapy (beginning day -6) and ASCT (Day 0). The first dose of 90Y-daclizumab will be fixed at 15 mCi. The second dose will be escalated in 15 mCi increments from 15 mCi until maximum tolerated dose, not to exceed 90 mCi.

• Phase II: All patients will receive two doses of 90Y-daclizumab (Day -56 and -15 2 days) followed by high-dose BEAM chemotherapy (beginning Day -6) and ASCT (Day 0). The first dose of RIT will be 15 mCi. The second dose will be the maximum tolerated dose as determined from phase I.

111In-daclizumab (5 mCi) imaging may be performed concurrently with each 90Ydaclizumab RIT and at day 100 after ASCT. ;

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

• NCT number: NCT01468311
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: October 11, 2011
• Completion date: October 22, 2020