I am still fairly new to RAC and being a shareholder. Still doing some research.
RAC hasn't made any announcements so far this month and Quarterly Report should be published by 30 April.
RAC made an announcement on 18 March 2020 that it had completed its recruitment for the clinical trial in Israel.
I have included below a snapshot from 3 clinical published AML clinical trials spanning from 1993 to 2019. Some observations from the results:
- CT#1: Feb 1993 - Bisantrene in relapsed and refractory acute myelogenous leukemia. Extract: "5 out of 7 patients achieved complete remission, one attained partial remission and one was resistant. However, haematological toxicity was severe with prolonged myelosuppression. Hepatic toxicity was the main extrahaematological side effect and occurred in 3 of 7 patients, however all of them recovered within 40 days.No cardiovascular dysfunction occurred although all the patients had been heavily previously treated with anthracyclines."
- ==> Note that the patients recovered from the toxicity with 40 days. Keep this in mind when I get to the 3 trial below. Also note that almost 40 days is almost gone by since RAC announced that recruitment for their 2020 trial had been achieved. Hopefully there is little to no toxicity showing in their patients. This is something I will be watching for when the results are announced. Very encouraging outcome overall.
- CT#2: 1994 - Treatment of relapsed or refractory acute leukemia in childhood with bisantrene combined with high dose aracytine. Extract: "The overall response rate was 46% with a 95% confidence interval ranging from 27-65%. According to diagnosis, complete remission (CR) rates are: AML: 5/13, ALL: 5/9, and AUL: 2/4. Four children died, three from infection and one from acute lysis syndrome.The major toxicity was infection with grade 3 and 4 episodes occurring in 42% of patients.No significant cardiac toxicity was noted.Hepatic and renal toxicity was noted. Hepatic and renal toxicity were limited and transient. Bisantrene in association with aracytine is effective in both AML and ALL of childhood.
- ==> Encouraging outcome overall.
- Another Drug / Not Bisantrene => CT#3: 2019 - FLAG/FLAG-IDA regimen for children with relapsed/refractory acute leukemia in the era of targeted novel therapies. Extract: " CONCLUSION:Despite a 68% complete remission rate using FLAG ± IDA, only 48% of patients survived to bone marrow transplantation. The regimen was associated with 96% toxicity and only one in four patients was alive at five years. This underscores the need to find more effective lower toxicity salvage regimens.
- ==> Results from that clinical trial were only announced 5 months ago. RAC maybe in the right place and the right time if the results of their Israel clinical trial prove successful with low or no ongoing toxicity level.
Here is more details about each of the 3 clinical trials discussed above.
---------------------------------------
Feb 1993
https://www.ncbi.nlm.nih.gov/pubmed/8471980
Leuk Lymphoma. 1993 Feb;9(3):217-20.
Bisantrene in relapsedand refractory acute myelogenous leukemia.
Spadea A1, Petti MC, Aloespiriti MA, Avvisati G, De Gregoris C, Fazi P, Latagliata R, Amadori S, Mandelli F.
Author information
Abstract
Because of the lack ofstandard treatment in refractory and relapsed acute myelogenous leukemia (AML)several new drugs have been employed alone to evaluate their efficacy in thispeculiar category of patient. Bisantrene, a new anthracene bishydrazonederivative, has shown antileukemic effect in phase I and II clinical trialswith acceptable extrahaematological toxicity. Seven patients (six males and onefemale, median age 41.8 years) received Bisantrene (250 mg/sqm/daily 1-7) as asingle agent in relapsed or refractory leukemia. 5 out of 7 patients achievedcomplete remission, one attained partial remission and one was resistant. However,haematological toxicity was severe with prolonged myelosuppression. Hepatictoxicity was the main extrahaematological side effect and occurred in 3 of 7patients, however all of them recovered within 40 days. No cardiovasculardysfunction occurred although all the patients had been heavily previouslytreated with anthracyclines. Our data confirm that Bisantrere is active inrelapsed and refractory AML and suggest the need for larger clinical trials tobetter evaluate its efficacy.
PMID: 8471980
DOI: 10.3109/10428199309147373
[Indexed for MEDLINE]
---------------------------------------
1994
https://www.ncbi.nlm.nih.gov/pubmed/8259097
Med PediatrOncol. 1994;22(2):119-24.
Treatment of relapsed orrefractory acute leukemia in childhood with bisantrene combined with high dosearacytine.
Leblanc T1, Deméocq F, Leverger G, Baruchel A, Lemerle S, Vannier JP, Nelken B, Guillot T, Schaison G.
Author information
Abstract
Bisantrene is ananthracene derivative which has demonstrated activity in acute myeloblastic leukemia(AML) and in lymphoma. The present study was designed to assess the reinductionrate and toxicity of bisantrene (250 mg/m2/d x 5) associated with aracytine(100 mg/m2 twice a day x 5) in refractory and relapsed acute childhoodleukemia. Patients who relapsed after bone marrow transplantation wereeligible. Twenty-six children were included. Diagnoses were as follows: 13 AML,9 acute lymphoblastic leukemia (ALL), and 4 undifferentiated leukemia (AUL).All patients had been very highly pretreated, especially with anthracyclines,and most of them were of poor prognosis. The overall response rate was 46% witha 95% confidence interval ranging from 27-65%. According to diagnosis, completeremission (CR) rates are: AML: 5/13, ALL: 5/9, and AUL: 2/4. Four childrendied, three from infection and one from acute lysis syndrome. The majortoxicity was infection with grade 3 and 4 episodes occurring in 42% ofpatients. No significant cardiac toxicity was noted. Hepatic and renal toxicitywas noted. Hepatic and renal toxicity were limited and transient. Bisantrene inassociation with aracytine is effective in both AML and ALL of childhood.Bisantrene should be evaluated with a five-day schedule in other pediatricmalignancies. In children with acute leukemia previously treated with high dosearacytine, new combination regimen is warranted.
PMID: 8259097
DOI:10.1002/mpo.2950220211
[Indexed for MEDLINE]
---------------------------------------
Dec 2019
https://www.ncbi.nlm.nih.gov/pubmed/30518307
J Oncol Pharm Pract. 2019 Dec;25(8):1831-1838. doi: 10.1177/1078155218817816. Epub 2018 Dec 5.
FLAG/FLAG-IDA regimen forchildren with relapsed/refractory acute leukemia in the era of targeted noveltherapies.
Mustafa O1, Abdalla K1, AlAzmi AA2, Elimam N1, Abrar MB1, Jastaniah W1,3.
Abstract
BACKGROUND:
Outcomes of relapsed/refractory childhoodacute leukemia remain poor. We analyzed the safety/efficacy of fludarabine,cytarabine, and granulocyte colony stimulating factor, with/without idarubicin(FLAG ± IDA) as salvage therapy compared with recent published results of noveltherapies.
METHODS:
This retrospective study included childrenaged 1 to 15 years with relapsed/refractory acute leukemia who receivedFLAG ± IDA salvage therapy from January 2000 to December 2014. Patients withinfant leukemia, mixed lineage leukemia, Philadelphia-positive acute leukemia,or secondary leukemia were excluded.
RESULT:
Fifty patients were identified: 25 with acutelymphoblastic leukemia and 25 with acute myeloid leukemia. The median age atinitiation of FLAG ± IDA was seven years. Site of relapse was the bone marrowin 29, isolated central nervous system in 11, and combined in 10 patients.FLAG ± IDA was used after first relapse in 68% and after multiple relapses in32%. Complete remission was achieved in 34 (68%) patients. No variablespredictive of complete remission were identified. Grade 3 or greater toxicitywas observed in 96% and 6% died from toxicity. Toxicities included hematologictoxicity (96%), infection (52%), and enterocolitis (28%). Twenty-four of 50(48%) patients achieved a sustained complete remission and survived to bonemarrow transplantation. The five-year overall survival was 23.9% ± 6.9%.Patients achieving second complete remission and patients proceeding to bonemarrow transplantation following second complete remission demonstrated significantlyimproved overall survival (p = 0.001).
CONCLUSION:
Despite a 68% complete remission rate usingFLAG ± IDA, only 48% of patients survived to bone marrow transplantation. Theregimen was associated with 96% toxicity and only one in four patients was aliveat five years. This underscores the need to find more effective lower toxicitysalvage regimens.
KEYWORDS:
Acute leukemia; FLAG; chemotherapy; refractory; relapse
PMID: 30518307
DOI: 10.1177/1078155218817816
[Indexed for MEDLINE]
-------------------------
(20min delay)