- |||||||||| RAPA-201 / Rapa Therap
Metabolically Reprogrammed Polyclonal Autologous Rapa-201 Cell Therapy Yields a Promising Safety and Efficacy Profile in Relapsed and Refractory Multiple Myeloma (RRMM) (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4483;
P2
Now, we are evaluating temsirolimus for manufacture of second-generation RAPA-201 cells...Bridging chemotherapy during manufacturing (Cycle 1) and host conditioning prior to RAPA-201 infusion consisted of the 14-day PC regimen [pentostatin (4 mg/m 2 IV; days 1, 4, 8, 12; dose adjusted/omitted with renal insufficiency); cyclophosphamide (100-200 mg PO, days 1-5 and days 8-12)]...RAPA-201 therapy represents a new paradigm that utilizes stringent mTOR inhibition to reprogram Th1/Tc1 cells for enhanced metabolic fitness and induction of in vivo T cell clonal expansion, thus providing an alternative to gene-modified targeted T cell therapy. With these promising safety and efficacy results, current RAPA-201 developmental efforts are directed towards completing protocol accrual in parallel with the design and implementation of next-generation clinical trials.
- |||||||||| pentostatin / Generic mfg.
Review, Journal: 1,3-Diazepine: A privileged scaffold in medicinal chemistry. (Pubmed Central) - Oct 30, 2021
It is present in the clinically used anticancer compound pentostatin, in several recent FDA approved β-lactamase inhibitors (e.g., avibactam) and also in coformycin, a natural product known as a ring-expanded purine analogue displaying antiviral and anticancer activities...This review endeavours to highlight the main use of the 1,3-diazepine scaffold and its derivatives, and their applications in medicinal chemistry, drug design, and therapy. We will focus more particularly on the development of enzyme inhibitors incorporating this scaffold, with a strong emphasis on the molecular interactions involved in the inhibition mechanism.
- |||||||||| cladribine / Generic mfg.
[VIRTUAL] RECURRENCE OF TRICHOLEUKEMIA TREATED WITH INTERFERON-α: CASE REPORT () - Oct 27, 2021 - Abstract #HEMO2021HEMO_1424;
The presentation is characterized by pancytopenia and splenomegaly, and approximately 25% of patients are asymptomatic. Diagnosis is established from peripheral blood and bone marrow examination (usually with dry puncture and need for bone marrow biopsy). Differential diagnosis includes variant hairy cell leukemia and splenic villous cell lymphoma, in addition to other myeloproliferative diseases (Primary Myelofibrosis) and infectious diseases (Leishmaniasis, for example).Case report We report the case of a male patient for 21 years. years she presented weakness and headache, in addition to changes in the blood count (sic). He underwent bone marrow biopsy and myelogram confirming the diagnosis of hairy cell leukemia. In another service, splenectomy was performed as a treatment for leukemia. After 4 years (1994) he presented a new episode of pancytopenia. A new bone marrow biopsy was performed, which revealed bone marrow fibrosis with significant hypocellularity and recurrence of hairy cell leukemia. Therefore, treatment with interferon alpha was started, with gradual clinical and hematological improvement, being treated for 2 years. He remained in remission for about 13 years when he came to our service. Gradually, the disease progressed and the cytopenias worsened, including the need for transfusion. With this new recurrence and the unavailability of Cladribine at that time, he was again treated with interferon alpha. The dose used was 3 million units subcutaneously 3 x per week. After 3 months, he presented resolution of the cytopenias and the regimen was maintained for about 2 and a half years. Toxicity was moderate with frequent fevers and mild depression possibly caused by the drug. Since then, he has been asymptomatic and has recently had the dose reduced to twice a week, then once a week, and currently in biweekly use. First-line therapy involves the use of Cladribine or Pentostatin, which are purine analogues. In earlier times, splenectomy was used as a therapy, being replaced by the advent of new pharmacological options. IFN-α is indicated in special cases, such as pregnancy and in difficult-to-control infection, in a transitory way, failure of the first-line treatment and recurrence in a short period of time. Although IFN-α associated with splenectomy is not the treatment of choice in Tricholeukemia, we report the case of a patient who responded well to therapy, with disease remission in the initial treatment and in two relapses.
- |||||||||| Rituxan (rituximab) / Roche
Trial primary completion date: Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia (clinicaltrials.gov) - Oct 26, 2021
P2, N=74, Recruiting,
years she presented weakness and headache, in addition to changes in the blood count (sic). He underwent bone marrow biopsy and myelogram confirming the diagnosis of hairy cell leukemia. In another service, splenectomy was performed as a treatment for leukemia. After 4 years (1994) he presented a new episode of pancytopenia. A new bone marrow biopsy was performed, which revealed bone marrow fibrosis with significant hypocellularity and recurrence of hairy cell leukemia. Therefore, treatment with interferon alpha was started, with gradual clinical and hematological improvement, being treated for 2 years. He remained in remission for about 13 years when he came to our service. Gradually, the disease progressed and the cytopenias worsened, including the need for transfusion. With this new recurrence and the unavailability of Cladribine at that time, he was again treated with interferon alpha. The dose used was 3 million units subcutaneously 3 x per week. After 3 months, he presented resolution of the cytopenias and the regimen was maintained for about 2 and a half years. Toxicity was moderate with frequent fevers and mild depression possibly caused by the drug. Since then, he has been asymptomatic and has recently had the dose reduced to twice a week, then once a week, and currently in biweekly use. First-line therapy involves the use of Cladribine or Pentostatin, which are purine analogues. In earlier times, splenectomy was used as a therapy, being replaced by the advent of new pharmacological options. IFN-α is indicated in special cases, such as pregnancy and in difficult-to-control infection, in a transitory way, failure of the first-line treatment and recurrence in a short period of time. Although IFN-α associated with splenectomy is not the treatment of choice in Tricholeukemia, we report the case of a patient who responded well to therapy, with disease remission in the initial treatment and in two relapses. Trial primary completion date: Oct 2022 --> Oct 2025
- |||||||||| pentostatin / Generic mfg.
Journal: Pentostatin Antagonizes the Antiviral Activity of MBX-2168 by Inhibiting the Biosynthesis of the Active Compound. (Pubmed Central) - Aug 28, 2021
As expected, incubation with dCF resulted in the accumulation of MBX-2168-MP in both HFF (9.8±0.9 pmol MBX-2168-MP/10 cells at 120 hours) and Vero cells (4.7±0.3 pmol MBX-2168-MP/10 cells at 24 hours) while no detectable levels of monophosphate were observed in cultures not incubated with dCF. We conclude that dCF antagonizes the anti-viral effect of MBX-2168 by inhibiting the production of triphosphate, the active compound.
- |||||||||| Campath (alemtuzumab) / Sanofi
Journal: Intensive Induction Therapy Compared With CHOP for Hepatosplenic T-cell Lymphoma. (Pubmed Central) - Aug 27, 2021
Non-CHOP-based induction appears superior to CHOP/CHOP-like induction in both achieving complete/partial response and durable survival. Induction therapy of HSTCL should be intensified with non-CHOP-based regimens and followed by consolidation with HSCT in eligible patients.
- |||||||||| cladribine / Generic mfg.
Review, Journal: Hairy Cell Leukaemia. (Pubmed Central) - Aug 20, 2021
HCLv has a worse prognosis with median overall survival (OS), only 7-9 years, despite the combination of PNA/rituximab improving front-line response. Moxetumomab or ibrutinib may be a viable treatment but lacks substantial evidence.
- |||||||||| Lumoxiti (moxetumomab pasudotox) / AstraZeneca, Innate, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche, Zelboraf (vemurafenib) / Roche
Clinical, Journal: Vemurafenib and Rituximab in Patients with Hairy Cell Leukemia Previously Treated with Moxetumomab Pasudotox. (Pubmed Central) - Jul 4, 2021
Two patients who had relapsed after vemurafenib and rituximab derived meaningful clinical benefit from retreatment with the same agents, but eventually relapsed again and started indefinite therapy with dabrafenib and trametinib leading to normalization of the blood counts (despite heavy bone marrow infiltration in the only patient so far evaluable in that regard). The outcomes of these cases indicate that novel targeted agents and, in particular, vemurafenib, combined with rituximab, improve the prognosis of HCL patients, even those heavily pretreated with PNAs and moxetumomab pasudotox.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Trial completion date, Trial primary completion date: A Blood Stem Cell Transplant for Sickle Cell Disease (clinicaltrials.gov) - Jun 28, 2021
P1, N=6, Recruiting,
The outcomes of these cases indicate that novel targeted agents and, in particular, vemurafenib, combined with rituximab, improve the prognosis of HCL patients, even those heavily pretreated with PNAs and moxetumomab pasudotox. Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024
- |||||||||| Campath (alemtuzumab) / Sanofi
Biomarker, Clinical, Clinical data, Journal: Clinical outcomes in T-cell large granular lymphocytic leukaemia: prognostic factors and treatment response. (Pubmed Central) - Jun 23, 2021
In this large, retrospective analysis, our results suggest Cy is a highly effective therapy for second-line treatment in T-LGLL and should be considered a strong candidate for up-front therapy in select high-risk patients. Prospective studies evaluating pentostatin, alemtuzumab and novel agents, such as duvelisib, are needed for patients with relapsed/refractory T-LGLL.
- |||||||||| cladribine / Generic mfg.
Clinical, Observational data, Journal: Targeted therapy for treatment of patients with classical hairy cell leukemia. (Pubmed Central) - Apr 24, 2021
BRAF inhibitor vemurafenib was started at 240-480 mg twice daily (planned 90-day treatment) and combined with rituximab in seven patients...Median progression free and overall survival was not reached at a median follow up of 18.1 months (range 3.2-68.9). These data suggest targeted therapy could be an option for patients unable to be treated with purine analogues.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Enrollment open: A Blood Stem Cell Transplant for Sickle Cell Disease (clinicaltrials.gov) - Mar 5, 2021
P1, N=6, Recruiting,
These data suggest targeted therapy could be an option for patients unable to be treated with purine analogues. Active, not recruiting --> Recruiting
- |||||||||| cordycepin (OVI-123) / OncoVista
Clinical, Review, Journal: Bioactive Metabolites and Potential Mycotoxins Produced by Cordyceps Fungi: A Review of Safety. (Pubmed Central) - Mar 3, 2021
Future elucidation of the compounds produced by these functionally unknown BGCs, and in-depth assessments of metabolite bioactivity and chemical safety, will not only facilitate the safe use of Cordyceps fungi as human food or alternative medicine, but will also benefit the use of mass production byproducts as animal feed. To corroborate the long record of use as a traditional medicine, future efforts will also benefit the exploration of Cordyceps fungi for pharmaceutical purposes.
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Review, Journal: Development of Recombinant Immunotoxins for Hairy Cell Leukemia. (Pubmed Central) - Feb 18, 2021
A phase 3 trial met its endpoint of durable CR with acceptable toxicity, leading to FDA approval of Moxe for relapsed/refractory HCL, under the name Lumoxiti. Moxe combined with rituximab is currently being evaluated in relapsed/refractory HCL to improve the rate of MRD-free CR.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Enrollment closed: A Blood Stem Cell Transplant for Sickle Cell Disease (clinicaltrials.gov) - Feb 8, 2021
P1, N=6, Active, not recruiting,
Despite being diagnosed incidentally in most of patients, T-PLL with t(X;14)(q28;q11.2) is an aggressive disease and patients with the disease have a dismal outcome. Recruiting --> Active, not recruiting
- |||||||||| Orencia (abatacept) / BMS
[VIRTUAL] A PERSONALIZED ORGAN-BASED APPROACH TO THE TREATMENT OF CHRONIC GRAFT-VERSUS-HOST DISEASE (On-Demand Library) - Feb 4, 2021 - Abstract #EBMT2021EBMT_1724;
In contrast, Pomalidomide, carfilzomib, and pentostatin were only effective in less than 23 percent in oral GvHD.Musculoskeletal-GvHD responded best to Ruxolitinib and Belomosudil at 100 and 73% respectively...For lung GvHD (BOS), 5/12 treatments reported a RR which was only 11-12% in those treated with Hydroxychloroquine, and Abatacept... Most of the GvHD trials conducted are focused on the overall response rate (ORR), partial, and complete response amongst transplant patients and the evidence for organ-specific response is limited and therefore our study results are striking for RR yields for some of the organs. Thus, a personalized organ-based approach to the selection of therapeutic agents in cGvHD can result in a more favorable patient outcome and achieving a better organ-specific response while minimizing toxicity and side effects.
- |||||||||| Orencia (abatacept) / BMS
[VIRTUAL] A PERSONALIZED ORGAN-BASED APPROACH TO THE TREATMENT OF CHRONIC GRAFT-VERSUS-HOST DISEASE (On-Demand Library) - Feb 4, 2021 - Abstract #EBMT2021EBMT_1723;
In contrast, Pomalidomide, carfilzomib, and pentostatin were only effective in less than 23 percent in oral GvHD.Musculoskeletal-GvHD responded best to Ruxolitinib and Belomosudil at 100 and 73% respectively...For lung GvHD (BOS), 5/12 treatments reported a RR which was only 11-12% in those treated with Hydroxychloroquine, and Abatacept... Most of the GvHD trials conducted are focused on the overall response rate (ORR), partial, and complete response amongst transplant patients and the evidence for organ-specific response is limited and therefore our study results are striking for RR yields for some of the organs. Thus, a personalized organ-based approach to the selection of therapeutic agents in cGvHD can result in a more favorable patient outcome and achieving a better organ-specific response while minimizing toxicity and side effects.
- |||||||||| Orencia (abatacept) / BMS
[VIRTUAL] A PERSONALIZED ORGAN-BASED APPROACH TO THE TREATMENT OF CHRONIC GRAFT-VERSUS-HOST DISEASE (On-Demand Library) - Feb 4, 2021 - Abstract #EBMT2021EBMT_1722;
In contrast, Pomalidomide, carfilzomib, and pentostatin were only effective in less than 23 percent in oral GvHD.Musculoskeletal-GvHD responded best to Ruxolitinib and Belomosudil at 100 and 73% respectively...For lung GvHD (BOS), 5/12 treatments reported a RR which was only 11-12% in those treated with Hydroxychloroquine, and Abatacept... Most of the GvHD trials conducted are focused on the overall response rate (ORR), partial, and complete response amongst transplant patients and the evidence for organ-specific response is limited and therefore our study results are striking for RR yields for some of the organs. Thus, a personalized organ-based approach to the selection of therapeutic agents in cGvHD can result in a more favorable patient outcome and achieving a better organ-specific response while minimizing toxicity and side effects.
- |||||||||| Orencia (abatacept) / BMS
[VIRTUAL] A PERSONALIZED ORGAN-BASED APPROACH TO THE TREATMENT OF CHRONIC GRAFT-VERSUS-HOST DISEASE (On-Demand Library) - Feb 4, 2021 - Abstract #EBMT2021EBMT_1721;
In contrast, Pomalidomide, carfilzomib, and pentostatin were only effective in less than 23 percent in oral GvHD.Musculoskeletal-GvHD responded best to Ruxolitinib and Belomosudil at 100 and 73% respectively...For lung GvHD (BOS), 5/12 treatments reported a RR which was only 11-12% in those treated with Hydroxychloroquine, and Abatacept... Most of the GvHD trials conducted are focused on the overall response rate (ORR), partial, and complete response amongst transplant patients and the evidence for organ-specific response is limited and therefore our study results are striking for RR yields for some of the organs. Thus, a personalized organ-based approach to the selection of therapeutic agents in cGvHD can result in a more favorable patient outcome and achieving a better organ-specific response while minimizing toxicity and side effects.
- |||||||||| Campath (alemtuzumab) / Sanofi
[VIRTUAL] Update on T-PLL in 2021 () - Jan 22, 2021 - Abstract #VLML2021VLML_35;
Nevertheless, these results highlight the need for novel therapies in T-PLL. Given the rarity of T-PLL, international, multicentre, randomised trials such as the ibrutinib and venetoclax trial are needed to improve outcomes.
- |||||||||| Campath (alemtuzumab) / Sanofi, Leustatin (cladribine) / J&J, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] Chronic Lymphocytic Leukemia Treatment in México: Up to Half Patients May Not Requiere Treatment () - Nov 5, 2020 - Abstract #ASH2020ASH_5269;
No patient had to be given cladribine, pentostatin, alemtuzumab (anti-CD52), bendamustine, ofatumumab (anti-CD20), obinutuzumab (anti-CD20), lenalidomide, ibrutinib nor idelalisib...In those needing treatment, the use of a simplified approach and taking advantage of improved supportive care measures, acceptable results are obtained even if all of the new CLL drugs are not employed. These observations may be critical in developing countries, where the cost of the drugs will continue to be a major factor in choosing therapies.
- |||||||||| pentostatin / Generic mfg.
[VIRTUAL] Renal Function Is Preserved after Hematopoietic Stem Cell Transplantation for Sickle Cell Disease (Channel 20 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_4295;
In an adjusted regression analysis, there was no association of gender, engraftment status, transplant regimen, or conditioning agent— specifically use of pentostatin, total body irradiation, or post-transplant cyclophosphamide— with worsening eGFR (p>0.05 for each variable)...The stability of UACR after an initial increase at the 1-year time point further suggests that even more mild renal damage may stabilize after transplant. Finally, AKI occurred in over half of the patients in our cohort, though the preponderance developed mild AKI.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Campath (alemtuzumab) / Sanofi
[VIRTUAL] Venetoclax Has Modest Efficacy in the Treatment of Patients with Relapsed T-Cell Prolymphocytic Leukemia (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_2550;
The 9 pts described herein represent the largest cohort of pts treated with venetoclax-based therapy in this setting to the current date. Despite initial reports of clinical efficacy, our results show that venetoclax (with or without bendamustine) has modest efficacy in the treatment of relapsed/refractory T-PLL after prior alemtuzumab exposure.
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