The New Drug Alisertib Performs Well in a Phase I Trial

“In a phase II study reported in The Lancet Oncology, Melichar et al found that the oral aurora kinase A inhibitor alisertib was active in solid tumors, particularly breast cancer and small cell lung cancer. Aurora kinases play central roles in mitosis. Inhibition of aurora kinase A, which is overexpressed/amplified in several tumor types and associated with poorer outcome, results in abnormal spindle formation, mitotic defects, and cell death.

“In the five-arm study, patients with disease that had relapsed or was refractory to chemotherapy and who had received up to two previous cytotoxic regimens (up to four for breast cancer), not including adjuvant or neoadjuvant treatment, were enrolled from 40 centers in the Czech Republic, France, Poland, and the United States between February 2010 and May 2013. Patients received alisertib at 50 mg twice daily for 7 days followed by 14 days off in 21-day cycles. Objective response was the primary endpoint.

“Among response-assessable patients, objective response (all partial responses) was observed in 9 (18%, 95% confidence interval [CI] = 9%–32%) of 49 women with breast cancer, 10 (21%, 95% CI = 10%–35%) of 48 patients with small cell lung cancer, 1 (4%, 95% CI = 0%–22%) of 23 with non–small cell lung cancer, 4 (9%, 95% CI = 2%–21%) of 45 with head and neck squamous cell carcinoma, and 4 (9%, 95% CI = 2%-20%) of 47 with gastroesophageal adenocarcinoma.”


Novel Cancer Drug Proves Safe for Leukemia Patients

The gist: Scientists tested a new leukemia drug in a clinical trial—a research study with volunteer patients. The drug is called CPI-613. In the trial, it was found to be safe and effective for people with leukemia that is relapsed (returned after treatment) or refractory (doesn’t respond to treatment). More research will be performed to better understand how well the drug works.

“Results of a Phase I clinical trial showed that a new drug targeting mitochondrial function in human cancer cells was safe and showed some efficacy. The findings, reported by doctors at Wake Forest Baptist Medical Center, are published in the current online edition of the journal Clinical Cancer Research.

” ‘This drug is selectively taken up by cancer cells and then shuts down the production of energy in the mitochondria,’ said Timothy Pardee, M.D., Ph.D., director of leukemia translational research at Wake Forest Baptist and principal investigator of the trial. ‘This is the first drug to inhibit mitochondria in this way and if it proves effective in further clinical trials, it will open up a whole new approach to fighting cancer.’ “


Clinical Trial to Test Safety of Drug Targeting Leukemia Cells

Editor’s note: Researchers have launched a new clinical trial—a research study with volunteer patients—to test a new drug to treat chronic lymphocytic leukemia (CLL). The drug is called cirmtuzumab (also known as UC-961). It targets a protein called ROR1, which is only found in tumors and helps them grow and metastasize. The researchers will enroll 33 to 78 patients with relapsed or refractory (does not respond to treatment) CLL, who will be treated with cirmtuzumab in San Diego.

“Researchers at the University of California, San Diego School of Medicine, in partnership with the California Institute for Regenerative Medicine (CIRM) and Celgene Corporation, a New Jersey-based biopharmaceutical company, have launched a phase 1 human clinical trial to assess the safety and efficacy of a novel monoclonal antibody for patients with chronic lymphocytic leukemia (CLL).

“CLL is the most common form of blood cancer in adults, with more than 15,000 new cases diagnosed each year in the United States. The new antibody targets ROR1, a protein used by embryonic cells during early development that is also exploited by cancer cells to promote tumor growth and metastasis – the spreading of cancer throughout the body that is responsible for 90 percent of all cancer-related deaths.

“ROR1 is not expressed by normal adult cells, making it a specific marker of cancer cells in general and cancer stem cells in particular. Because ROR1 is a primary driver of tumor growth and metastasis, researchers believe it presents an excellent target for anti-cancer therapy.

“Developed at UC San Diego Moores Cancer Center by Thomas Kipps, MD, PhD, who holds the Evelyn and Edwin Tasch Chair in Cancer Research, and colleagues, the antibody is called cirmtuzumab (also known as UC-961). In previous animal studies, Kipps’ team reported that ROR1 is singularly expressed on CLL and also on a variety of different cancers, including cancers of the breast, pancreas, colon, lung and ovary. In mouse models of CLL, ROR1 acts as an accelerant when combined with another oncogene to produce a faster-growing, more aggressive cancer.”


Bortezomib/Lenalidomide Combination Therapy Evaluated in Relapsed/Refractory Mantle Cell Lymphoma

Editor’s note: This article describes the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to test the effectiveness of a mantle cell lymphoma treatment that combines the drugs bortezomib (Velcade) and lenalidomide (Revlimid). Specifically, the trial tested the treatment for patients whose cancer did not get better after previous treatments or whose cancer returned after treatment. The results of the clinical trial were “disappointing.” The combination treatment was less effective than either drug on its own.

“Although the majority of patients with mantle cell lymphoma respond to initial therapy, the duration of remission is typically short (1.5 to 3 years). Although bortezomib (Velcade) and lenalidomide (Revlimid) as single agents have been associated with response rates as high as 53% in patients with relapsed/refractory disease, Morrison et al reported an overall response rate of almost 40% with combination bortezomib/lenalidomide therapy in an article published in Leukemia & Lymphoma.

“The incidence of mantle cell lymphoma has increased dramatically over the past several decades. The median overall survival is 3 to 6 years with standard chemotherapy approaches, and fewer than 15% of patients are long-term survivors.

“Therefore, researchers continue to investigate newer therapeutic options for these patients. One such approach was the combination of bortezomib and lenalidomide, particularly in patients who experienced relapse from or were refractory to previous treatments. In the phase II CALGB 50501 trial, a team of investigators from the University of Minnesota, Duke University, Dana-Farber Cancer Institute, Ohio State University, Washington University, and Georgetown University attempted to evaluate the feasibility of combination treatment with bortezomib and lenalidomide in patients with relapsed or refractory mantle cell lymphoma.”


Elacytarabine Failed to Improve Outcomes in Relapsed/Refractory AML

Editor’s note: This article covers recent research that hoped to identify good treatments for people with acute myeloid leukemia that has relapsed (returned after initial treatment) or is refractory (resistant to initial treatment). Unfortunately, neither a new drug called elacytarabine nor seven other treatments showed any benefits for the patients involved in the study. One of the researchers said that patients with relapsed/refractory acute myeloid leukemia should be treated in clinical trials whenever possible. Clinical trials are studies with volunteer patients to test promising new treatments. They have risks and advantages, but they can let patients receive cutting-edge drugs they might not otherwise be able to take.

Excerpt:

“Neither the novel agent elacytarabine nor seven other commonly used salvage regimens provided clinically meaningful benefit to patients with relapsed/refractory acute myeloid leukemia, according to results of a phase 3 study.

“ ‘The data from our work sadly reaffirm, on a global basis, the dismal prognosis of patients with relapsed/refractory AML,’ Gail J. Roboz, MD, director of the leukemia program and associate professor of medicine at Weill Cornell Medical College and New York-Presbyterian Hospital, and colleagues wrote. ‘There is no effective standard of care, and patients with this disease should be treated on clinical trials whenever feasible. ‘”


FDA Grants Breakthrough Designation to Personalized Immunotherapy for ALL

“The FDA today granted breakthrough therapy designation for CTL019, an investigational personalized immunotherapy, for the treatment of relapsed and refractory adult and pediatric acute lymphoblastic leukemia, according to a press release issued by Penn Medicine.

“CTL019 (Novartis), developed by the University of Pennsylvania, is the first personalized cellular therapy for the treatment of cancer to receive this classification.

“In early-stage clinical trials conducted at the Hospital of the University of Pennsylvania and Children’s Hospital of Philadelphia, 89% of patients with ALL who were not responding to conventional therapies achieved complete remission after treatment with CTL019.

“ ‘Our early findings reveal tremendous promise for a desperate group of patients, many of whom have been able to return to their normal lives at school and work after receiving this new, personalized immunotherapy,’ Carl H. June, MD, director of translational research in the Abramson Cancer Center of the University of Pennsylvania. ‘Receiving the FDA’s Breakthrough Designation is an essential step in our work with Novartis to expand this therapy to patients across the world who desperately need new options to help them fight this disease.’ ”

Editor’s note: This story describes a new leukemia treatment called CTL019, which boosts a patient’s own immune system to fight cancer. CTL019 treatment is personalized for each patient, since it involves altering a patient’s immune system cells to attack tumor cells. It has been tested in volunteer patients in clinical trials, and has shown promising results for adults and children with relapsed or refractory acute lymphoblastic leukemia (ALL). The U.S. Food and Drug Administration (FDA) has now granted breakthrough therapy designation for CTL019, meaning that review and approval will be accelerated so that the drug can more quickly reach patients outside of clinical trials.


FDA Approves Spectrum Pharma's Blood Cancer Drug

“Spectrum Pharmaceuticals Inc’s drug for the treatment of an aggressive form of blood cancer was granted an accelerated approval by the U.S. Food and Drug Administration on Thursday.

“The drug, Beleodaq, has been approved for patients with peripheral T-cell lymphoma, a rare cancer of the lymph nodes. (1.usa.gov/1iZVgY6)

“The regulator grants an accelerated approval to a drug based on initial trials that show the medicine’s benefit for patients with serious conditions with few or no treatment options.

“Upon approval, the drug is subject to trials that must confirm its benefit…

“The drug is intended for patients who have either relapsed or have not responded to prior treatment.”


Blinatumomab Receives Breakthrough Therapy Designation for ALL

“The FDA has granted a breakthrough therapy designation to blinatumomab for the treatment of adult patients with Philadelphia-negative relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), according to Amgen, the company developing the drug.

“The breakthrough therapy designation was based on results from a phase II trial of 189 patients. As of January 2014, 43% (n = 82) of patients achieved a complete remission (CR) or CR with partial hematological recovery (CRh). These results were presented at the 2014 ASCO Annual Meeting and at the 19th Congress of the European Hematology Association.

” ‘There is a high unmet need for new medicines to treat relapsed and refractory ALL patients, who have very few treatment options,’ Sean E. Harper, MD, executive vice president, Research and Development, Amgen, said in a statement. ‘The results from the phase II trial evaluating blinatumomab in adult patients with relapsed or refractory ALL are encouraging and provide a strong basis for a regulatory filing later this year and potential approval in this serious disease.’ ”

Editor’s note: Blinatumomab is a new drug that is being tested as a potential treatment for people with acute lymphoblastic leukemia (ALL) that is resistant to treatment (refractory) or that has returned after treatment (relapsed). Based on promising research results, blinatumomab has received a Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA), specifically for adults with relapsed or refractory B-precursor ALL that is Philadelphia-negative. This means that the FDA finds the drug to be very promising compared to currently available treatments, and will accelerate the approval process that would ultimately permit U.S. oncologists to prescribe the drug outside of a clinical trial.


Karyopharm Initiates Registration-Directed, Randomized Study Of Selinexor (KPT-330) In Older Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)

“Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company focused on the discovery and development of novel first-in-class drugs directed against nuclear transport targets for the treatment of cancer and other major diseases, today announced the initiation of its Phase 2 study of Selinexor (KPT-330) in patients 60 years of age or older with relapsed or refractory acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy and/or transplantation. This S elinexor in O lder P atients with R elapsed/Refractory A ML (SOPRA) study is a randomized trial of Selinexor, the company’s novel oral Selective Inhibitor of Nuclear Export (SINE) compound, versus physician’s choice, and will be conducted at approximately 40 sites worldwide including sites in the United States, Canada, Europe and Israel.”

Editor’s note: This story is about a clinical trial to test a potential new treatment for relapsed or refractory acute myelod leukemia (AML) in volunteer patients. The trial is testing whether a drug called Selinexor (aka KPT-330) is effective for patients 60 years of age or older who, for whatever reason, cannot be treated with intensive chemotherapy and/or transplantation. 2/3 of the participating patients will take Selinexor, and for comparison, 1/3 will receive a different standard treatment. The trial is randomized, meaning that patients cannot choose which treatment they receive.