Phase 1 trial study of 131I-labeled chimeric 81C6 monoclonal antibody for the treatment of patients with non-Hodgkin lymphoma

Blood ◽  
2004 ◽  
Vol 104 (3) ◽  
pp. 642-648 ◽  
Author(s):  
David A. Rizzieri ◽  
Gamal Akabani ◽  
Michael R. Zalutsky ◽  
R. Edward Coleman ◽  
Scott D. Metzler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase 1 ◽  
Absorbed Dose ◽  
Whole Body ◽  
Hematologic Toxicity ◽  
Blocking Antibody ◽  
Non Hodgkin Lymphoma ◽  
Body Activity ◽  
The Mean ◽  
Administered Activity

AbstractWe report a phase 1 study of pharmacokinetics, dosimetry, toxicity, and response of 131I anti-tenascin chimeric 81C6 for the treatment of lymphoma. Nine patients received a dosimetric dose of 370 MBq (10 mCi). Three patients received an administered activity of 1480 MBq (40 mCi), and 2 developed hematologic toxicity that required stem cell infusion. Six patients received an administered activity of 1110 MBq (30 mCi), and 2 developed toxicity that required stem cell infusion. The clearance of whole-body activity was monoexponential with a mean effective half-life of 110 hours (range, 90-136 hours) and a mean effective whole-body residence time of 159 hours (range, 130-196 hours). There was rapid uptake within the viscera; however, tumor uptake was slower. Activity in normal viscera decreased proportional to the whole body; however, tumor sites presented a slow clearance (T1/2, 86-191 hours). The mean absorbed dose to whole-body was 67 cGy (range, 51-89 hours), whereas the dose to tumor sites was 963 cGy (range, 363-1517 cGy). Despite lack of a “blocking” antibody, 1 of 9 patients attained a complete remission and 1 a partial remission. These data demonstrate this radiopharmaceutical to be an encouraging agent for the treatment of lymphoma particularly if methods to protect the normal viscera are developed.

Safety and feasibility of rhenium-186 nanoliposome (186RNL) in recurrent glioma: The ReSPECT phase 1 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2061-2061
Author(s):  
Andrew J. Brenner ◽  
Ande Bao ◽  
William Phillips ◽  
Gregory Stein ◽  
Vibhudutta Awasthi ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Tumor Volume ◽  
Phase 1 ◽  
Absorbed Dose ◽  
External Beam Radiation ◽  
Whole Body ◽  
Recurrent Glioma ◽  
Normal Brain ◽  
Beam Radiation ◽  
The Mean

2061 Background: While external beam radiation therapy (EBRT) remains a central component of the management of primary brain tumors, it is limited by tolerance of the surrounding normal brain tissue. Rhenium-186 NanoLiposome (186RNL) permits the delivery of beta-emitting radiation of high specific activity with excellent retention in the tumor. We report the results of the phase 1 study in recurrent glioma. Methods: A Phase 1 dose-escalation study of 186RNL in recurrent glioma utilizing a standard 3+3 design was undertaken to determine the maximum tolerated dose of 186RNL. 186RNL is administered by convection enhanced delivery (CED). Infusion is followed under whole body planar imaging and SPECT/CT. Repeat SPECT/CT imaging is performed immediately following, and at 1, 3, 5, and 8 days after 186RNL infusion to obtain dosimetry and distribution. Subjects were followed until disease progression by RANO criteria. Results: Eighteen subjects were treated across 6 cohorts. The mean tumor volume was 9.4 mL (range 1.1 – 23.4). The infused dose ranged from 1.0 mCi to 22.3 mCi and the volume of infusate ranged from 0.66 mL to 8.80 mL. From 1 – 4 CED catheters were used. The maximum catheter flow rate was 15 µl/min. The mean absorbed dose to the tumor volume was 239 Gy (CI 141 – 337; range 9 - 593), to normal brain was 0.72 Gy (CI 0.34 – 1.09; range 0.005 – 2.73), and to total body was 0.07 Gy (CI 0.04 – 0.10; range 0.001 – 0.23). The mean absorbed dose to the tumor volume when the percent tumor volume in the treatment volume was 75% or greater (n = 10) was 392 Gy (CI 306 – 478; range 143 – 593). Scalp discomfort and tenderness related to the surgical procedure did occur in 3 subjects. The therapy has been well tolerated, no dose-limiting toxicity has been observed, and no treatment-related serious adverse events have occurred despite markedly higher absorbed doses typically delivered by EBRT in patients with prior treatment. Responses have been observed supporting the clinical activity. Final results from the dose escalation will be presented. Conclusions: 186RNL administered by CED to patients with recurrent glioma results in a much higher absorbed dose of radiation to the tumor compared to EBRT without significant toxicity. The recommended Phase 2 dose is 22.3 mCi in 8.8 mL of infusate. Clinical trial information: NCT01906385. [Table: see text]

scholarly journals RADT-24. HIGH ABSORBED DOSES OF RHENIUM-186 NANOLIPOSOMES (RNL) IN RECURRENT GBM: A PHASE 1 STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii186-ii186
Author(s):  
Andrew Brenner ◽  
John Floyd ◽  
Ande Bao ◽  
William Phillips ◽  
Vibhudutta Awasthi ◽  
...  
Keyword(s):  
Phase 1 ◽  
High Specific Activity ◽  
Absorbed Dose ◽  
External Beam Radiation ◽  
Whole Body ◽  
Recurrent Glioma ◽  
Normal Brain ◽  
Beam Radiation ◽  
Absorbed Doses ◽  
The Mean

Abstract INTRODUCTION While external beam radiation therapy (EBRT) remains a central component of the management of primary brain tumors, it is limited by tolerance of the surrounding normal brain tissue. Nanoliposomal BMEDA-chelated-186Rhenium (RNL™) permits the delivery of beta-emitting radiation of high specific activity with excellent retention in the tumor. We report on the phase 1 results in recurrent glioma. METHODS A phase 1 dose-escalation study of RNL in recurrent glioma utilizing a standard 3 + 3 design was undertaken to determine the maximum tolerated dose of RNL following stereotactic biopsy. RNL is administered with the BrainLab Flexible Catheter by convection enhanced delivery (CED) with placement guided using iPlan Flow and the Varioguide system. Infusion is followed under whole body planar imaging and SPECT/CT. Repeat SPECT/CT imaging is performed immediately following, and at 1, 3, 5, and 8 days after RNL infustion to obtain dosimetry and distribution. RESULTS Thirteen patients have been treated to-date, 12 were recurrent glioblastoma, and 54% failed treatment with bevacizumab. The infused dose was progressively increased from 1.0 mCi to 13.4 mCi and the volume of infusate from 1.0 mL to 5.28 mL using 1 – 2 CED catheters. The mean absorbed dose to the distribution volume was 175 Gy (CI 97 – 254). The maximum absorbed dose to the tumor volume was 593 Gy. The mean retention of the administered dose at 24 hours was 61.4% (CI 45.4 – 77.5). The therapy has been well tolerated and no dose-limiting toxicity has been observed with no treatment related adverse effects despite markedly higher absorbed doses than EBRT in patients with prior treatment. The plan is to increase the dose to 22.3 mCi and the infusate volume to 8.8 mL. CONCLUSION Intratumoral RNL can deliver up to twenty times the absorbed dose of radiation administered by EBRT without significant toxicity.

scholarly journals Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma

2020 ◽  
Vol 4 (17) ◽  
pp. 4091-4101
Author(s):  
Arne Kolstad ◽  
Tim Illidge ◽  
Nils Bolstad ◽  
Signe Spetalen ◽  
Ulf Madsbu ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase 1 ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Overall Response ◽  
Non Hodgkin Lymphoma ◽  
Anti Cd20

Abstract For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20–based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the “cold” anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

Phase 1 Dose-Escalation Study of 90yttrium-Labeled Anti-CD22 Epratuzumab Tetraxetan in Adults with Refractory/Relapsed CD22+ B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3708-3708
Author(s):  
Patrice Chevallier ◽  
Thomas Eugene ◽  
Nelly Robillard ◽  
Françoise Isnard ◽  
Franck E Nicolini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Phase 1 ◽  
Whole Body ◽  
Organ Distribution ◽  
Hematologic Toxicity ◽  
Level 3 ◽  
Level 1 ◽  
Level 2

Abstract Background: Prognosis of relapsed/refractory acute lymphoblastic leukemia (ALL) in adults is dismal. CD22 is highly expressed in patients with B-ALL. Epratuzumab (hLL2) is a humanized monoclonal antibody targeting CD22 surface antigen. We performed a standard 3+3 phase 1 study to assess the feasibility, tolerability, and efficacy of a 90yttrium-labeled anti-CD22 epratuzumab tetraxetan (90Y-DOTA-hLL2) radioimmunotherapy (RIT) in adults with refractory/relapsed CD22+ B-ALL. Methods: After premedication with corticosteroid, 90Y-DOTA-hLL2 was administered twice on days 1 and 8 (+2), successively at 2.5 (level 1), 5.0 (level 2), 7.5 (level 3), and 10.0 (level 4) mCi/m². The first two patients also received 4 infusions of DOTA-hLL2 360 mg/m²/day before the RIT. This “cold phase” was terminated after observing no efficacy and full saturation of the CD22 target on the leukemic cells. Minimal residual disease (MRD) was assessed either by flow cytometry or by RQ-PCR for BCR-ABL1 analyses in Philadelphia chromosome positive (Ph+) B-ALL patients. Dose-limiting toxicity (DLT) was defined as any non-reversible grade >3 non-hematological toxicity or grade 4 pancytopenia with hypocellular bone marrow lasting for >6 weeks. Maximum tolerated dose (MTD) was defined as the dose level at which 2 of 3 or 2 of 6 patients experienced a DLT. Dosimetry, organ distribution and elimination of the radiotracer were studied between the two RIT infusions in all but one patient, using whole-body scintigraphy recorded after 111Indium-epratuzumab tetraxetan injection and blood pharmacokinetics. Patients were evaluated for response between 4 and 6 weeks following the first infusion of RIT. Findings: Between October 2011 and June 2014, 20 patients were enrolled. Three patients were not considered for analyses because of disease progression (n=2) or persistent non-blastic pancytopenia (n=1) before RIT. Overall, 17 cases were treated (5 at level 1 including 2 previously treated with the cold phase, 3 at level 2, 3 at level 3, and 6 at level 4). There were 10 males and 7 females with a median age of 62 years (range: 27-77). Two patients had primary refractory B-ALL; 10, 3 and 2 were in first, second or third relapse, respectively. Median percentage of blasts in the bone marrow was 75%. Karyotypes were as follows: Ph+ B-ALL n=6, complex n=3, MLL rearrangement n=1, hyperdiploidy n=1, hypodiploidy n=1, near-triploidy n=1, del4q (+ikaros mutation) n=1, normal (but ikaros mutation) n=1, and unknown n=2. Four patients were previously allotransplanted. Median interval between diagnosis and RIT was 16.5 months. Five patients presented immediate infusion reactions (3 grade 1, 1 grade 2 and 1 grade 3 in a patient with a previous history of severe allergic reactions) after the first RIT infusion, but received the second infusions without toxicities. All examined patients showed expected uptake of the radiotracer on potential disease sites (blood, spleen, liver, and bone marrow). No response was seen at levels 1 and 3. One molecular complete response was documented at level 2 (54-year old woman in third relapse of Ph+ B-ALL). At level 4, 2 patients achieved complete remissions (1 Ph+ ALL and 1 Ph- ALL), while all 6 cases presented with grade 4 hematologic toxicity. One DLT was documented at level 4 (non-blastic pancytopenia lasting 8 weeks), but MTD was not reached. Two patients in response received a second RIT cycle. Currently, only one non-responder is alive, while 2 of 3 responders are alive. One relapsed at 1 year and died of progression (level 2), while the two remaining are in persistent CR at 6 months post RIT, with low positive MRD. Interpretation: 90Y-DOTA-hLL2 RIT is well-tolerated and induced complete remissions even in heavily pre-treated CD22+ relapsed/refractory B-ALL patients, thus appearing to be a promising targeted therapy for CD22+ B-ALL. We recommend the dose of 10 mCi/m² given twice, one week apart/cycle, for phase 2 studies. The trial is registered at http://clinicaltrials.gov/ct no.NCT01354457. Funding: Immunomedics, Inc. Disclosures Goldenberg: immunomedics: Employment. Wegener:immunomedics: Employment.

Phase 1 Study of Radiosensitization Using Bortezomib in Patients with Relapsed Non-Hodgkin's Lymphoma Receiving Radioimmunotherapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1636-1636
Author(s):  
Rebecca L. Elstrom ◽  
John P. Leonard ◽  
Paul Christos ◽  
Peter Martin ◽  
Daniel Lebovic ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
Whole Body ◽  
Hematologic Toxicity ◽  
Advisory Committees ◽  
Off Label ◽  
Grade 3 ◽  
Indolent Lymphomas ◽  
131I Tositumomab

Abstract Abstract 1636 Background: Radioimmunotherapy (RIT) is effective treatment for relapsed and refractory indolent lymphomas. Results in aggressive lymphomas such as diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) have been less impressive, with lower response rates and short duration of response. We hypothesized that administration of the proteasome inhibitor bortezomib as a radiosensitizer in patients receiving RIT would be tolerable and potentially improve efficacy in both aggressive and indolent lymphomas. Methods: We performed a Phase 1 dose escalation study to evaluate the maximum tolerated dose (MTD) of bortezomib in combination with 131I-tositumomab. The study underwent review and was approved by each institution's Institutional Review Board. Dose escalation proceeded using a Time to Event-Continuous Reassessment Model (TiTE-CRM). Patients with relapsed or refractory DLBCL, MCL or indolent B cell non-Hodgkin's lymphoma were eligible if they had not undergone prior stem cell transplant, organ function was preserved, and bone marrow involvement by lymphoma was less than 25% of the intertrabecular space. Neutrophil count at least 1500/uL and platelet count at least 150 × 103/uL were required. A dosimetric dose of 131I-tositumomab was administered on day 1, followed by three whole body gamma camera scans for purposes of dose calculation and evaluation of biodistribution. After an initial cohort received a reduced whole-body dose of 50 cGy 131I-tositumomab, patients received RIT at the standard dose of 75 cGy on day 8. Patients were treated with escalating doses of bortezomib (0.3 to 1.2 mg/m2) on days 6, 10, 13, 16 and 20. Dose limiting toxicity (DLT) was defined as any grade 3 or 4 non-hematologic toxicity, or grade 4 hematologic toxicity. Results: The study has completed enrollment, with 25 patients having received study treatment. These include 8 patients with DLBCL, 5 with MCL, 11 with follicular lymphoma (FL), and one with marginal zone lymphoma (MZL). Median age is 68 (range 40–81). Median number of prior therapies is 2 (range 1–4), and all but one had received prior rituximab. Twenty-three patients are evaluable for response, while two patients have not yet undergone restaging. Twenty-four patients are evaluable for the primary endpoint of MTD. One treated patient was not evaluable for toxicity due to early progression of disease and need for further therapy prior to the end of the observation period. Of 24 patients evaluable, 4 experienced DLT (Table), all at dose level 5 (1.2 mg/m2). These events included grade 3 hyponatremia, herpes zoster, and grade 4 thrombocytopenia. Grade 3 hematologic toxicities included two patients with leukopenia, three with neutropenia, one with anemia, and five with thrombocytopenia. Dose level 4 (0.9 mg/m2 bortezomib, 75 cGy 131I-tositumomab) was well tolerated, and this dose was identified as the MTD. Fourteen of 23 (61%) patients evaluable for response have responded, including 3/8 with DLBCL, 3/5 with MCL, and 8/9 with FL. Ten patients have achieved complete remission, including one patient with DLBCL, one with MCL, and 8 with FL. At median follow up of 8 months, median progression free survival is 6 months, and seven patients (50% of responders) remain in remission at 2 to 28 months. Conclusions: Bortezomib can be safely administered in combination with 131I-tositumomab. Responses were seen in a majority of patients, including those with aggressive histology. The MTD has been defined as 0.9 mg/m2 bortezomib plus 75 cGy 131I-tositumomab. This strategy of radiosensitization using bortezomib shows promise, and efficacy should be further evaluated in a Phase 2 trial. Disclosures: Off Label Use: Azacitidine is approved for use in MDS. Discussion here is off label. Leonard:Glaxo SmithKline: Consultancy, Honoraria. Martin:Cephalon: Consultancy; Celgene: Consultancy; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lebovic:Genentech: Speakers Bureau. Coleman:Celgene Corp: Speakers Bureau. Kaminski:GlaxoSmithKline: Patents & Royalties, Research Funding.

Repeat Treatment with Iodine-131-Rituximab Is Safe and Effective in Patients with Relapsed Indolent B-Cell Non-Hodgkin Lymphoma (NHL) Who Had Previously Responded to This Therapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3413-3413
Author(s):  
Mark J. Bishton ◽  
Michael F. Leahy ◽  
Rod J. Hicks ◽  
J. Harvey Turner ◽  
Ad McQuillan ◽  
...  
Keyword(s):  
B Cell ◽  
Haematological Toxicity ◽  
Absorbed Dose ◽  
Response Duration ◽  
Complete Response ◽  
Thyroid Stimulating Hormone ◽  
Whole Body ◽  
Hematologic Toxicity ◽  
Small Series ◽  
Grade 3

Abstract Aims. A recent multi-center phase II trial of I131 rituximab treatment for patients (pts) with relapsed or refractory indolent B-cell NHL demonstrated an overall response rate (ORR) of 76%, with 53% attaining a complete response (CR) or CR unconfirmed (CRu). Small series suggest re-treatment with murine anti-CD20 radio-immunotherapy (Bexxarä, Zevalinä) may be safe and effective. Humanized antibodies have a longer half-life than murine antibodies, potentially prolonging bone marrow radio-isotope exposure, potentially leading to cumulative myelo-suppression on re-treatment. We therefore retrospectively analysed data from two institutions on the safety and efficacy of re-treatment with 131I-rituximab in pts with relapsed or refractory indolent CD20 positive B-cell NHL. Methods. All pts who had been treated with two or more episodes of 131I-rituximab were identified from the institutional databases from January 2000 to July 2007. Pts received two unlabeled doses of rituximab 375mg/m2 and individualized 131-I-rituximab doses estimated to deliver a whole-body radiation absorbed dose of 0.75 Gy. Pts were monitored with weekly full blood counts until 12 wks post-therapy or recovery from nadir levels, and thyroid function was routinely monitored at follow-up visits. Following treatment, the severity and duration of cytopenias was noted, as was the development of myelodysplasia (MDS) and acute myeloid leukemia (AML), as well as elevated thyroid stimulating hormone (TSH) and/or a low free thyroxine (T4). We compared the response duration following first and second treatments and haematological toxicity. Results. Sixteen pts [follicular (15), mantle cell (1)] who had previously responded to RIT were re-treated with I131 rituximab [median inter-treatment interval 19 months (9–54)]. There were no grade 3/4 adverse reactions during re-treatment infusion with 131I-rituximab, and in particular no anaphylaxis occurred. There was an ORR of 88%, with a 56% CR rate and by Kaplan-Meier analysis 36% of all retreated pts were estimated to be progression-free at 12 months. Six pts had longer remissions with the second treatment than their first. The time to progression post second treatment (median 11 months) was not significantly different from the first treatment (median 14 months; P=0.89). Rates of Grade 3/4 hematologic toxicity were neutropenia 29% and thrombocytopenia 27% respectively, and did not differ from first treatment (both 25%). There were no infectious complications requiring hospital admission and only one patient required packed cell transfusion. Three pts have subsequently required thyroxine supplementation, but no cases of thyroid cancer have occurred. AML was diagnosed in one pt at 28 months, although this patient had previously been treated with chlorambucil, and had a mild macrocytosis consistent with an early MDS prior to their first RIT. No cases of MDS were seen. Conclusions. Re-treatment with 131I-rituximab is an efficacious and safe option for pts who have responded previously to 131I-rituximab. Myelo-suppression was unchanged from first exposure. Durable responses may be achieved despite modest TTP following the initial treatment.

Lenalidomide and Rituximab Following Autologous Stem Cell Transplantation for B-Cell Non-Hodgkin Lymphoma Is Associated with Unacceptable Myelotoxicity

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1621-1621
Author(s):  
Robert Dean ◽  
Brad Pohlman ◽  
Lisa Rybicki ◽  
Amanda L. Maggiotto ◽  
Jennifer Bates ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Maintenance Therapy ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Dose Level ◽  
Hematologic Toxicity ◽  
Non Hodgkin Lymphoma ◽  
Level 1 ◽  
Dose Limiting Toxicity

Abstract Abstract 1621 Relapse remains the principal cause of treatment failure following high-dose chemotherapy with autologous stem cell transplantation (ASCT) in patients with B-cell non-Hodgkin lymphoma (NHL). There is a significant unmet need for an intervention that could effectively reduce the risk of relapse after ASCT. Pilot studies suggest that maintenance therapy with the anti-CD20 monoclonal antibody rituximab may increase progression-free survival after ASCT for NHL. The immunomodulatory drug lenalidomide increases rituximab-induced cytotoxicity in preclinical models. Both agents have clinical activity in B-cell NHL singly and in combination, and both are well-tolerated with generally manageable hematologic and other acute toxicities. In addition, lenalidomide and rituximab have each been used extensively as maintenance treatments for lymphoproliferative disorders following ASCT or chemotherapy-based induction therapies, respectively. Therefore, we initiated a prospective phase I clinical trial of post-transplant maintenance therapy using lenalidomide and rituximab. Eligibility criteria included: diagnosis of B-cell NHL; ASCT within the preceding 70 days; post-transplant staging with stable disease, partial response, or complete remission; resolution of transplant-related non-hematologic toxicities to NCI CTC grade ≤ 2; absolute neutrophil count at least 1,500/uL and platelet count 75,000/mm3 (grade ≤ 1); ECOG performance status ≤ 2. Subjects received lenalidomide PO on days 1–21 of 28-day cycles, with rituximab administered IV on day 1 of every other treatment cycle, for up to 12 cycles. Dose-limiting toxicity (DLT) was defined as potentially drug-related grade 4 hematologic or grades 3–4 non-hematologic toxicities during cycle 1 of study treatment. Five subjects were enrolled from 1/2010 through 11/2010: 2 at dose level 1 (lenalidomide 10 mg, rituximab 375 mg/m2) and 3 at dose level-1 (lenalidomide 5 mg, rituximab 375 mg/m2). Diagnoses included diffuse large B-cell (N=3) or mantle cell (N=2) lymphoma. Subjects began on-study treatment from 68 to 123 days after ASCT (median 93 days). Four subjects experienced DLT consisting of fatal pneumonitis (1 subject at dose level 1) or grade 4 neutropenia (1 subject at dose level 1, and 2 subjects at dose level-1). Three of these subjects discontinued treatment during cycle 1, per protocol. One subject completed 3 full cycles, with reduction within cycle 1 to dose level-1 because of grade 4 neutropenia, and halting treatment per protocol during cycle 4 because of grade 2 retinal vein thrombosis. One subject completed 4 cycles of treatment at dose level-1 before discontinuing per protocol because of grade 4 neutropenia. The study was closed due to dose-limiting toxicity at the lowest dose level. There was no relationship between bone marrow morphology before ASCT and hematologic toxicity on study. All subjects were in remission at study entry, without evidence of marrow involvement by lymphoma, and therefore none was evaluable for response to treatment. No surviving subject has progressed, with median follow-up of 9.5 months from study entry. We conclude that maintenance therapy with lenalidomide and rituximab is tolerated poorly in the early recovery period following ASCT, owing mainly to unacceptable hematologic toxicity. Further studies would be of interest to evaluate the feasibility of this regimen if introduced later following ASCT, or to determine the tolerability of lenalidomide alone in this setting. Disclosures: Dean: Genentech: Honoraria. Off Label Use: Lenalidomide is not approved for the treatment of NHL.

Kinetics and dosimetry of MAb-170: Evaluation of possibilities for intraperitoneal radioimmunotherapy

2001 ◽  
Vol 40 (06) ◽  
pp. 207-214 ◽  
Author(s):  
M. Holländer ◽  
W. Schmidt ◽  
C.-M. Kirsch ◽  
Ch. Alexander
Keyword(s):  
Bone Marrow ◽  
Residual Disease ◽  
Whole Body ◽  
Second Phase ◽  
Recent Experience ◽  
Worst Case ◽  
Red Bone Marrow ◽  
Elimination Half ◽  
Body Activity ◽  
The Mean

SummaryThe monoclonal antibody MAb-170 is directed against adenocarcinomas of different origin. Recent experience in radioimmunoscintigraphy revealed a positive uptake of this MAb in peritoneal metastases of ovarian carcinoma (FIGO lll/IV). Aim: The present investigation should clarify the question whether this antibody could be of use in an adjuvant intraperitoneal radioimmunotherapy (RIT) in patients with minimal residual disease after first-look surgery. Methods: Four patients underwent intraperitoneal application of Tc-99m MAb-170. Subsequent quantitative whole-body scintigraphy, serum and urine sampling were performed for a 48 h period. In one case tumour tissue specimen were sampled during the first surgical procedure 15 h p.L Results: The quantitative evaluation revealed no relevant accumulation in liver, spleen and bone marrow never exceeding 5 % of the whole-body activity. The critical organs are the kidneys that showed 8 to 11 % uptake at 24 h pi. The effective serum curve had a maximum at 24 h pi, the second phase gave a elimination half-time of 53 h. Assuming the worst case, the mean dose to red bone marrow was 0.3 Gy/370 MBq injected dose (ID). Conclusion: These results confirm that a RIT with Re-186 MAb-170 is feasible with activities of up to 3.7 GBq. A kit for labelling MAb-170 with Perrhenate is under investigation.

scholarly journals Blood dosimetry from a single measurement of the whole body radioiodine retention in patients with differentiated thyroid carcinoma

2009 ◽  
Vol 16 (4) ◽  
pp. 1283-1289 ◽  
Author(s):  
Heribert Hänscheid ◽  
Michael Lassmann ◽  
Markus Luster ◽  
Richard T Kloos ◽  
Christoph Reiners
Keyword(s):  
Absorbed Dose ◽  
Differentiated Thyroid Carcinoma ◽  
Whole Body ◽  
Simple Method ◽  
Remnant Ablation ◽  
Body Retention ◽  
Body Activity ◽  
Body Counting ◽  
Simple Formalism ◽  
Whole Body Counting

A simple method is presented to estimate the radiation-absorbed dose to the blood after radioiodine administration from a single external measurement of the whole-body retention in patients suffering from differentiated thyroid cancer. The blood dose is calculated applying the formalism of the Medical International Radiation Dose Committee under the assumptions that whole-body activity decays exponentially and that 14% of the whole-body residence time can be attributed to the blood. Accuracy and applicability of the method were tested based on data from 29 assessments, 18 pre-therapeutic tracer studies, and 11 ablation therapies, with whole-body and blood-retention measurements over at least 4 days. The mean of the absolute deviations between estimates and actual blood doses was found to be 14%, if external whole-body counting was performed on day 1 or 2 after radioiodine administration. This simple formalism is: 1) applicable to pre-therapeutic dosimetry for remnant ablation or treatment of metastases in a blood dose-based treatment concept and 2) applicable to blood-dose estimates after radioiodine therapy to determine radiation exposure. When combined with a measurement of the whole body retention 1 or 2 days after radioiodine administration this single time-point method closely approximates the classic, yet much more labor intensive multi-day dosimetry that measures both blood and whole-body activities.

Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphoma

Blood ◽  
2004 ◽  
Vol 104 (1) ◽  
pp. 227-236 ◽  
Author(s):  
Andres Forero ◽  
Paul L. Weiden ◽  
Julie M. Vose ◽  
Susan J. Knox ◽  
Albert F. LoBuglio ◽  
...  
Keyword(s):  
Fusion Protein ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Phase 1 ◽  
Whole Body ◽  
Single Chain ◽  
Phase 1 Trial ◽  
Non Hodgkin Lymphoma ◽  
Pretargeted Radioimmunotherapy ◽  
Anti Cd20

Abstract Pretargeted radioimmunotherapy (PRIT) has the potential to increase the dose of radionuclide delivered to tumors while limiting radiation to normal tissues. The purpose of this phase 1 trial is to assess safety of this multistep approach using a novel tetrameric single-chain anti-CD20–streptavidin fusion protein (B9E9FP) as the targeting moiety in patients with B-cell non-Hodgkin lymphoma (NHL), and to characterize its pharmacokinetics and immunogenicity. All patients received B9E9FP (160 mg/m2 or 320 mg/m2); either 48 or 72 hours later, a synthetic clearing agent (sCA) was administered (45 mg/m2) to remove circulating unbound B9E9FP. 90Yttrium (90Y; 15 mCi/m2)/111In (5 mCi)–DOTA-biotin was injected 24 hours later. There were 15 patients enrolled in the study. B9E9FP had a mean plasma half-life (T½) of 25 ± 6 hours with a reduction in plasma level of more than 95% within 6 hours of sCA administration. 90Y/111In-DOTA-biotin infusion resulted in rapid tumor localization and urinary excretion. The ratio of average tumor to whole-body radiation dose was 49:1. No significant hematologic toxicities were noted in 12 patients. There were 2 patients who had hematologic toxicity related to progressive disease. There were 2 complete remissions (90 and 325 days) and one partial response (297 days). B9E9FP performs well as the targeting component of PRIT with encouraging dosimetry, safety, and efficacy. A dose escalation trial of 90Y-DOTA-biotin in this format is warranted.

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