No Signs of New Toxicity When Amphotericin B Lipid Complex (ABLC, ABELCET) and Caspofungin Are Used in Combination in the Treatment of FUO.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5077-5077
Author(s):  
Rodrigo Martino ◽  
Bertrand DuPont ◽  
Helen Huckle ◽  
Raj Chopra
Keyword(s):  
Renal Failure ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Single Agent ◽  
Study Drug ◽  
Immunocompromised Patients ◽  
Multi Centre Study ◽  
Therapy Regimen ◽  
Grade 3 ◽  
Experienced Grade

Abstract BACKGROUND: Systemic fungal infections including invasive candidiasis and aspergillosis are a significant cause of mortality and morbidity in immunocompromised patients. ABLC is used for the treatment of fungal infections in patients who are intolerant or unresponsive to conventional amphotericin therapy. Caspofungin is a second-line treatment for invasive aspergillosis. The different mechanisms of action of these agents support a dual-therapy regimen; synergistic results have been observed in vitro (Arikan et al, Antimicrob Agents Chemother, 2002;46:245–47). The aim of this open-label, multi-centre study was to investigate safety, tolerability (primary endpoints) and efficacy of concomitant ABLC and caspofungin in immunocompromised patients with refractory FUO (fever of unknown origin). METHODS: At baseline patients were required to have serum creatinine≤220 μm/L, neutrophil count <0.5x109/L, and at least 72 hours of fever refractory to antibiotics or a recurrence of fever despite continuing antibiotics. Patients received an initial 70 mg caspofungin IV over one hour, followed by ABLC 5 mg/kg IV over 4 hours, then caspofungin 50 mg/day and ABLC 5mg/kg/day. Medication continued until apyrexia or the patient was withdrawn from the study. Tolerability was assessed through incidence and severity of adverse events (AE) including study withdrawal due to Aes. There was a 30-day follow-up period. RESULTS: 27 immunocompromised patients (mean age 48.9, 18 male) entered the study (leukemia without transplant in 68.2% of patients, haematological malignancy with transplant in 27.3% of patients). Extent of exposure was 11.9 days (mean) for ABLC and 12.2 days (mean) for caspofungin. Safety: 27 patients were assessed for safety. 18.6% of Aes were considered related to study drug. Drug related Aes included hypokalaemia (4.9%), nausea (4.4%), rigours (4.0%), renal failure (3.5%), diarrhoea (3.5%), hypomagnesaemia (3.1%) and oliguria (1.3%). Three patients experienced grade 3 hypokalaemia related to study medication. Two patients experienced study drug related grade 3 renal failure. This is a similar incidence to single agent use of lipid-associated amphotericin B. The two patients who received concomitant ciclosporin did not develop renal toxicity. Tolerability: 22 patients were assessed (5 were excluded; 1 protocol violator (inclusion criteria), 2 had fewer than 7 doses of drug and 2 died, reasons unrelated to study drug). 20 (90.9%) patients completed the study without grade 4 or unresolved grade 3 AE. No patient experienced grade 4 AE related to the study drug. No patient withdrew from the study due to AE’s. Efficacy: 20 patients were assessed (2 patients withdrew consent before study completion). All patients achieved a normal median daily temperature after a mean of 4.3 days (range 2–16 days). CONCLUSIONS: There was no evidence of newly emerging toxicity associated with the combination of ABLC and caspofungin and no evidence of increase in known toxicity. In addition there is evidence that the combination was efficacious, but there is a clear need for additional studies to confirm this finding.

Nivolumab/pembrolizumab in Child-Pugh grade B/C patients with advanced HCC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16184-e16184
Author(s):  
Jeffrey Sum Lung Wong ◽  
Gin Wai Kwok ◽  
Vikki Tang ◽  
Bryan Li ◽  
Roland Ching-Yu Leung ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Median Number ◽  
Refractory Ascites ◽  
Time To Progression ◽  
Advanced Hcc ◽  
Grade 3 ◽  
Experienced Grade ◽  
Systemic Therapies

e16184 Background: Hepatic derangement commonly accompanies advanced HCC (aHCC) and limits the use of systemic therapies. We aimed to evaluate the use of single agent anti-PD-1 nivolumab or pembrolizumab in Child-Pugh (CP) grade B or C patients with aHCC. Methods: Consecutive aHCC patients with CP grade B (CPB) or C (CPC) liver function who received single agent nivolumab or pembrolizumab were analysed. Objective response rate (ORR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed. Results: Between May 2015 and June 2020, 61 patients were included. The median age was 60 (range 28-82). 81% and 4.8% had hepatitis-B and hepatitis-C related HCCs respectively. 72.1% (n = 44) were of CPB and 27.9% (n = 17) were of CPC. Amongst CPB patients, 19 (31.1% of all patients) had CP score 7 (CP7) and 25 (41.0% of all patients) had CP score 8 or 9. The median follow-up was 2.3 months. The ORR of CPB and CPC patients were 6.8% and 0% respectively (p = 0.553). The TTP of CPB and CPC patients were 2.1 months (95% C.I. 1.4-2.8) and 1.4 months (95% C.I. 0.6-2.1) respectively (p = 0.204). CPB patients had significantly better OS than CPC patients (3.1 months (95% C.I. 1.4-4.7), vs. 1.7 months (95% C.I. 1.0-2.4), p = 0.041). Compared to CP score ≥8 (CP≥8) patients, CP7 patients had significantly better OS (median OS CP7 6.7 months (95% C.I. 4.0-9.3), vs. CP≥8 1.8 months (1.2-2.4), p = 0.002). Patients with diuretic-refractory ascites had significantly worse OS compared to those without (1.7 months (95% C.I. 1.0-2.5) vs. 3.7 months (95% C.I. 0.1-7.3), p = 0.004). Portal vein (PV) thrombosis was also significantly associated with inferior survival, with median OS of patients with any PV thrombosis being 1.8 months (95% C.I. 1.0-2.5), compared to 5.3 months (95% C.I. 2.4-8.1) of those without (p = 0.004). The median number of doses given was 3 (range 1-34). Median treatment duration was 5.0 weeks (range 0-77). Overall, 25.4% of patients experienced TRAEs and 4.8% experienced grade ≥3 TRAEs. The most common TRAEs were skin-related (13.1%) and constitutional symptoms (6.6%). Conclusions: Nivolumab/pembrolizumab had acceptable safety in CPB/C patients with aHCC. CP7, absence of diuretic-refractory ascites and lack of PV thrombosis were associated with better survival.

scholarly journals Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients

2010 ◽  
Vol 54 (10) ◽  
pp. 4143-4149 ◽  
Author(s):  
Andreas H. Groll ◽  
Gerda Silling ◽  
Charlotte Young ◽  
Rainer Schwerdtfeger ◽  
Helmut Ostermann ◽  
...  
Keyword(s):  
Stem Cell ◽  
Combination Therapy ◽  
Adverse Events ◽  
Amphotericin B ◽  
Hematopoietic Stem Cell ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Study Drug ◽  
Invasive Fungal Infections ◽  
Hematopoietic Stem

ABSTRACT The combination of liposomal amphotericin B (LAMB) and caspofungin (CAS) holds promise to improve the outcome of opportunistic invasive mycoses with poor prognosis. Little is known, however, about the safety and pharmacokinetics of the combination in patients at high risk for these infections. The safety and pharmacokinetics of the combination of LAMB and CAS were investigated in a risk-stratified, randomized, multicenter phase II clinical trial in 55 adult allogeneic hematopoietic stem cell recipients (aHSCT) with granulocytopenia and refractory fever. The patients received either CAS (50 mg/day; day 1, 70 mg), LAMB (3 mg/kg of body weight/day), or the combination of both (CASLAMB) until defervescence and granulocyte recovery. Safety, development of invasive fungal infections, and survival were assessed through day 14 after the end of therapy. Pharmacokinetic sampling and analysis were performed on days 1 and 4. All three regimens were well tolerated. Premature study drug discontinuations due to grade III/IV adverse events occurred in 1/18, 2/20, and 0/17 patients randomized to CAS, LAMB, and CASLAMB, respectively. Adverse events not leading to study drug discontinuation were frequent but similar across cohorts, except for a higher frequency of hypokalemia with CASLAMB (P < 0.05). Drug exposures were similar for patients receiving combination therapy and those randomized to monotherapy. There was no apparent difference in the occurrence of proven/probable invasive fungal infections and survival through day 14 after the end of therapy. CASLAMB combination therapy in immunocompromised aHSCT patients was as safe as monotherapy with CAS or LAMB and had similar plasma pharmacokinetics, lending support to further investigations of the combination in the management of patients with invasive opportunistic mycoses.

Cladribine Activity in Adult Langerhans-Cell Histiocytosis

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4125-4130 ◽  
Author(s):  
Alan Saven ◽  
Carol Burian
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Overall Response Rate ◽  
Single Agent ◽  
Langerhans Cell ◽  
Median Response ◽  
Major Activity ◽  
Prior Surgery ◽  
Grade 3 ◽  
Experienced Grade

Abstract Langerhans-cell histiocytosis (LCH) results from the accumulation of tissue histiocytes derived from the same progenitor cells as monocytes. Because cladribine is potently toxic to monocytes, we conducted a phase II trial of cladribine. Cladribine was administered to 13 LCH patients at 0.14 mg/kg per day by 2-hour intravenous infusion for 5 consecutive days, every 4 weeks for a maximum of six courses. Median age was 42 years (range, 19 to 72) and median pretreatment disease duration was 99 months (range, 6 to 252). One patient was untreated, one had received prior prednisone only, one prior radiation only, six prior radiation and chemotherapy, and four prior surgery, radiation, and chemotherapy. Seven patients had cutaneous involvement, six multifocal osseous, six pulmonary, two each with soft tissue and nodal involvement, and four had diabetes insipidus. Of 13 patients, 12 were evaluable for response and all for toxicity. After a median of three courses (range, 1 to 6), seven (58%) patients achieved complete responses (two pathologic and five clinical) and two (17%) patients achieved partial responses; overall response rate, 75%. Median response follow-up duration was 33 months (range, 1 to 65). Seven patients experienced grade 3 to 4 neutropenia. Only one patient had a documented infection, dermatomal herpes zoster. At a median follow-up of 42 months (range, 5 to 76), 12 patients remain alive and one patient has died. Thus, cladribine has major activity in adult LCH and warrants further investigation in both pediatric and adult LCH as a single agent and in combination with other drugs.

Phase I Trial of CG53135-05 to Prevent Mucositis in Patients Undergoing High-Dose Chemotherapy (HDCT) and Autologous Peripheral Blood Stem Cell Transplantation (PBSCT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1161-1161
Author(s):  
Michael W. Schuster ◽  
Tsiporah B. Shore ◽  
June Greenberg ◽  
Bita Jalilizeinali ◽  
Scott Possley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase I ◽  
Oral Mucositis ◽  
Phase I Trial ◽  
Study Drug ◽  
Great Promise ◽  
Cell Transplant ◽  
Conditioning Regimens ◽  
Grade 3 ◽  
Experienced Grade

Abstract Mucositis is a painful side effect of many transplant conditioning regimens used in HDC and PBSCT. This complication often requires treatment with potent narcotic analgesics and may even require intravenous patient-controlled analgesia (PCA) for adequate pain relief as well as total parenteral nutrition (TPN). Infections in this setting may also result from disruption of the mucosal barrier with subsequent migration of intestinal bacteria into the blood stream. Previous treatments with oral rinses and topical applications of soothing gels have largely been ineffective. Recently, a breakthrough class of drugs in the fibroblast growth factor (FGF) family holds great promise in more effectively ameliorating or even preventing oral mucositis (OM). We report on the results of a Phase I trial with CG53135-05, a novel investigational protein therapeutic (FGF-20) that promotes epithelial and mesenchymal cell proliferation in vitro and has demonstrated activity in animal models. 14 patients (ages 25–75) undergoing HDCT with PBSCT were treated with escalating doses of study drug, including 0.1 mg/kg, 0.2 mg/kg and 0.33 mg/kg (concentrations are determined by the UV method which are equivalent to 0.3, 0.6, and 1 mg/kg by the Bradford method previously used). Conditioning regimens used included melphalan (Mel 200), cyclophosphamide, carmustine and etoposide (CBV), carboplatin and thiotepa (CT), cyclophosphamide, etoposide and carmustine (CEC) and busulfan/cyclophosphamide (targeted BuCy). The primary objective of this phase I trial was to evaluate safety, tolerability and pharmacokinetics of CG53135-05. Patients (pts.) were also scored daily for presence of OM using both the WHO and OMAS (oral mucositis assessment scale) grading scales. 7/14 pts. in this study experienced no OM (including 2 Mel 200 patients), 5 pts. experienced only grade 1 OM. while 2 pts. (both treated with Mel 200) experienced grade 3 OM, and no pts. experienced grade 4 OM. 1 pt. experiencing grade 3 OM required TPN. Only 4 pts. experienced diarrhea that lasted more than 4 days and only 1 pt. had gut mucositis-associated (E. coli) bacteremia. The median day of engraftment (ANC&gt;500/uL) occurred on day 14 (range: day 11–19). Patients tolerated the study drug well with no significant side effects up to a dose of 0.33 mg/kg. At that dose, 2 pts. experienced an infusional reaction consisting of fevers, nausea, and mild hypotension. Pharmacokinetics were measured at all dose levels and will be presented. CG53135-05 is a member of a breakthtrough drug class (FGF family) that was well tolerated in autologous stem cell transplant patients at doses up to 0.33 mg/kg with apparent clinical effects in ameliorating or preventing OM - 12/14 pts, thus, avoided severe (grades 3–4) mucositis following HDCT. A larger Phase II clinical trial is planned.

Liposomal Amphotericin B IV (LIPO AB) Once Per Week Is Effective in the Prevention of Invasive Fungal Infections (IFI) in Patients (Pts) with Acute Leukemia: Preliminary Analysis of a Randomized Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1824-1824
Author(s):  
Gloria Mattiuzzi ◽  
Jorge Cortes ◽  
Deborah Blamble ◽  
Elihu Estey ◽  
Hagop Kantarjian
Keyword(s):  
Adverse Events ◽  
Randomized Trial ◽  
Fungal Infections ◽  
Performance Status ◽  
Study Drug ◽  
Disease Status ◽  
Myelogenous Leukemia ◽  
Remission Induction ◽  
Drug Discontinuation ◽  
Grade 3

Abstract Background: IFI remain an important cause of morbidity and mortality in pts with acute myelogenous leukemia or high risk myelodysplastic syndrome (AML/HR-MDS). We have previously shown that voriconazole (VORI) or LIPO AB 3 mg/kg/day TIW were effective prophylactic regimens in AML/HR-MDS. LIPO AB given once every week achieves tissue levels expected to prevent IFI, decreases the risk for infusion-related adverse events (IRE) and would simplify prophylaxis. Materials and Methods: We conducted a 3-arm randomized trial comparing LIPO AB, 3 mg/kg/d TIW (LIPO AB 3); versus LIPO AB 9 mg/kg/d, 1/week (LIPO AB 9); versus VORI 200 mg PO 2/day among pts with AML/MDS undergoing induction or salvage chemotherapy (CHEMO). Pts were stratified by age and disease status and randomized to receive any of the 3 regimens 24 hours after completion of CHEMO. Serum Galactomannan Index (GMI) was obtained 2/week while CT scan of chest (CT) was performed for persistent fever after 3 days of broad spectrum antibiotics. Proven and probable IFI were defined according to EORTC/MSG criteria. The results of the first 59 pts (of 150 planned) enrolled between Dec 06 -July 07 are presented. Results: Pts characteristics and response are shown in Table 1. All pts had Zubrod performance status ≤ 2 and most underwent remission induction chemo (90% in each group). No significant differences were observed on key baseline characteristics. Three of the 59 pts did not receive study drug (AMBI 9=2; VORI=1) and were excluded from efficacy and safety analysis. There were no proven IFI; 3 pts developed probable pulmonary Aspergillosis [GMI(+); CT (+), cultures (−) ], while 10 pts received additional empirical antifungal therapy (AFT) because of FUO [ 7 pts; GMI (−), CT (−), cultures (−)] or pneumonia [ 3 pts; GMI (−), cultures (−)]. None of these 10 pts developed proven/probable IFI. Two pts in each study arm developed reversible side effects that lead to drug discontinuation [AMBI 3: Grade 2 hyperbilirubinemia (1); Grade 3 infusion related events (1); AMBI 9: Grade 3 infusion related event (2); VORI: Grade 2 hyperbilirubinemia (1), visual hallucinations (1)]. Overall mortality was 5% (1 pt/arm). There were no IFI-related deaths. Conclusion: Intermittent LIPO AB (3 mg/kg/d TIW or 9 mg/kg/d, 1/week) and VORI 200 mg PO 2/day prophylaxis appear to be effective and well-tolerated regimens. Enrollment of additional pts is ongoing. Table 1 LIPO AB 3 (n=20) LIPO AB 9 (n=20) VORI (n=19) *p=ns; **p=0.061 Median age* (range) 60 (40–79) 60 (23–69) 58 (31–77) Pts in protected environment* (%) 80 65 79 Diabetes mellitus**, n(%) 1 (5) 1 (5) 5 (26) Median days on prophylaxis* (range) 17 (1–34) 14 (1–37) 17 (1–37) Efficacy and adverse events LIPO AB 3 (n=20) LIPO AB 9 (n=18) VORI (n=18) No IFI*, n(%) 14 (70) 14 (78) 15 (83) Proven/Probable IFI*, n(%) 2 (10) 1 (5) 0 Empiric AFT*, n(%) 4 (10) 3 (17) 3 (17) Adverse events*, n 4 4 3 All drug-related*, n(%) 2 (10) 2 (11) 2 (11)

Cladribine Activity in Adult Langerhans-Cell Histiocytosis

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4125-4130 ◽  
Author(s):  
Alan Saven ◽  
Carol Burian
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Overall Response Rate ◽  
Single Agent ◽  
Langerhans Cell ◽  
Median Response ◽  
Major Activity ◽  
Prior Surgery ◽  
Grade 3 ◽  
Experienced Grade

Langerhans-cell histiocytosis (LCH) results from the accumulation of tissue histiocytes derived from the same progenitor cells as monocytes. Because cladribine is potently toxic to monocytes, we conducted a phase II trial of cladribine. Cladribine was administered to 13 LCH patients at 0.14 mg/kg per day by 2-hour intravenous infusion for 5 consecutive days, every 4 weeks for a maximum of six courses. Median age was 42 years (range, 19 to 72) and median pretreatment disease duration was 99 months (range, 6 to 252). One patient was untreated, one had received prior prednisone only, one prior radiation only, six prior radiation and chemotherapy, and four prior surgery, radiation, and chemotherapy. Seven patients had cutaneous involvement, six multifocal osseous, six pulmonary, two each with soft tissue and nodal involvement, and four had diabetes insipidus. Of 13 patients, 12 were evaluable for response and all for toxicity. After a median of three courses (range, 1 to 6), seven (58%) patients achieved complete responses (two pathologic and five clinical) and two (17%) patients achieved partial responses; overall response rate, 75%. Median response follow-up duration was 33 months (range, 1 to 65). Seven patients experienced grade 3 to 4 neutropenia. Only one patient had a documented infection, dermatomal herpes zoster. At a median follow-up of 42 months (range, 5 to 76), 12 patients remain alive and one patient has died. Thus, cladribine has major activity in adult LCH and warrants further investigation in both pediatric and adult LCH as a single agent and in combination with other drugs.

Phase II trial of oral gimatecan in adults with recurrent glioblastoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2009-2009
Author(s):  
J. Hu ◽  
P. Y. Wen ◽  
L. E. Abrey ◽  
C. Fadul ◽  
J. Drappatz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Single Agent ◽  
Recurrent Glioblastoma ◽  
Hematologic Toxicity ◽  
Radiographic Response ◽  
Daily Dose ◽  
Grade 3 ◽  
Experienced Grade

2009 Background: Gimatecan is a highly lipophilic oral camptothecin analogue with impressive preclinical activity in glioma models. Methods: We conducted a multicenter two-stage phase II trial to evaluate the efficacy of gimatecan in adults with recurrent glioblastoma. Eligibility criteria included ≤1 prior treatment for recurrent disease, age ≥18, ECOG performance status 0 or 1, and normal organ function. Patients taking enzyme-inducing anti-seizure medications were excluded. Gimatecan 1.22 mg/m2 was given orally once daily for 5 consecutive days during each 28-day cycle. Radiographic response was evaluated by MRI after every second cycle. The primary endpoint of the study was 6 months PFS. A Simon's 2-stage design was used in which 19 patients were evaluated in the first stage, with an additional 36 patients accrued if > 4 patients in stage 1 achieved 6 month PFS. Results: A total of 29 patients were enrolled in the study, with median age of 58 years (range, 25–77 years); 58.6% female; all of whom had received prior surgery, radiation therapy, and at least one regimen of chemotherapy. The daily dose was reduced to 1.0 mg/m2 after four of the first 10 patients experienced grade 4 hematologic toxicity. One patient was removed from trial due to toxicity (grade 3 leukopenia and thrombocytopenia). Treatment delay occurred in 11 patients (38%) and dose reduction was necessary in eight patients (28%). Treatment-related grade 3/4 toxicities included thrombocytopenia (17.2%), leukopenia (17.2%), and neutropenia (10.3%). Only 1/19 patients treated with 1.0 mg/m2/day experienced grade 3/4 hematologic toxicity. The 18% reduction in the daily dose resulted in a 19% decrease in the concentration of total gimatecan in plasma prior to administration of the fifth daily dose (56 ± 23 vs. 45 ± 20 ng/mL) and a 33% decrease in the AUC for dose 5 (8.0±4.8 vs. 5.3±4.2 ng*h/mL). Only one patient had a partial radiographic response by the modified Macdonald criteria and stable disease was the best response in 13 patients. All other patients had progressive disease after two cycles of therapy. Only three patients (12%) were progression-free at 6 months. Median time to progression was 12.0 weeks (95% CI: 7.0, 17.0). Conclusions: Treatment with single-agent gimatecan 1.0 mg/m2/day for 5 days, repeated every 28-days showed minimal efficacy. [Table: see text]

A phase I study of the first-in-class mitochondrial metabolism inhibitor CPI-613 in patients with advanced hematologic malignancies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2516-2516
Author(s):  
Timothy S. Pardee ◽  
Denise A. Levitan ◽  
David Duane Hurd ◽  
Leslie R. Ellis ◽  
Scott Isom ◽  
...  
Keyword(s):  
Renal Failure ◽  
Stable Disease ◽  
Hospice Care ◽  
Single Agent ◽  
Therapeutic Index ◽  
Hematologic Malignancies ◽  
Phase Ii Trials ◽  
Heavily Pretreated ◽  
Altered Metabolism ◽  
Grade 3

2516^ Background: Altered metabolism is a hallmark of cancer, including hematologic malignancies. This altered metabolism is a possible therapeutic target. The lipoate derivative CPI-613 is a first in class agent that targets pyruvate dehydrogenase complex.This trial was designed to determine the maximally tolerated dose (MTD), safety, and efficacy of CPI-613 given as a single agent by IV infusion. Methods: CPI-613 was given over a 2 hour infusion on days 1 and 4 for 3 weeks every 28 days with a starting dose of 420 mg/m2. The dose was escalated in 6 cohorts to a final dose of 3780 mg/m2. Treatment could be continued if the patient experienced clinical benefit. Results: A total of 26 patients with advanced relapsed or refractory hematologic malignancies were enrolled. Patients were heavily pretreated with a median of 3 previous therapies (range 1-11). CPI-613 was well tolerated when infused over 2 hours, with no worsening of cytopenias at any dose level. After the dose was escalated to 2940 mg/m2 the protocol was amended to a 1 hour infusion. When infused over 1 hour, 2 patients developed grade 3 renal failure. Infusion time was then returned to 2 hours and dose escalation resumed. At a dose of 3780 mg/m2, one patient experienced prolonged grade 3 nausea and one patient grade 3 renal failure, defining this dose as above the MTD. Renal failure resolved in all but one patient who opted for hospice care. A total of 6 patients were treated at a dose of 2940 mg/m2over 2 hours with no DLTs observed, establishing this as the MTD. Of the 21 patients evaluable for a response, eight achieved a response of stable disease or better for a response rate of 38%. Responses included a complete remission maintained over 27 cycles in one AML patient and clearance of marrow blasts in another, sustained partial response in both a Burkitt's and a cutaneous T cell lymphoma patient maintained over 17 and 8 cycles respectively, and stable disease in 2 multiple myeloma and 2 myelodysplasia patients. Conclusions: To our knowledge this is the first report of an agent with activity in aggressive hematological malignancies that is not myelosuppressive. The therapeutic index appears high suggesting CPI-613 should be further studied in phase II trials. Clinical trial information: NCT01034475.

scholarly journals A treated case of rhinocerebral zygomycosis with aspergillosis: a case report from India

2020 ◽  
Vol 2 (8) ◽  
Author(s):  
Shalini Malhothra ◽  
Sabyasachi Mandal ◽  
Rajkumari Meena ◽  
Priti Patel ◽  
Nirmaljit Kaur Bhatia ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Fungal Infections ◽  
Clinical Sample ◽  
Rapid Diagnosis ◽  
Arterial System ◽  
Immunocompromised Patients ◽  
Direct Examination ◽  
Intravenous Amphotericin ◽  
Endoscopic Debridement ◽  
Prompt Diagnosis

Zygomycosis and aspergillosis are two serious fungal infections that are commonly seen in immunocompromised patients. Since both of these infections involve fungi that invade vessels of the arterial system, an early and rapid diagnosis by direct examination of KOH mounts of the relevant clinical sample can clinch the diagnosis. Here, we present a case of a 60-year-old diabetic patient who presented with swelling and pain over the nose and left eye for 7 days with loss of vision in the left eye. After investigation, the patient was diagnosed as having rhinocerebral mucormycosis and aspergillosis, and was initially treated with amphotericin B (1 mg kg−1 day−1 intravenously), followed by endoscopic debridement under general anaesthesia. The patient gradually improved after surgery, and treatment with intravenous amphotericin B was continued along with the addition of 200 mg oral voriconazole twice daily (for the aspergillosis). With prompt diagnosis and treatment, the patient survived these fatal fungal co-infections and finally was discharged.

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