Recently in Clinical Trials Category

 A phase 2 clinical trial of a targeted therapy provides evidence that there might, at last, be a treatment that shrinks or stifles the growth of recurrent low-grade serous ovarian cancer.

Women who have low-grade disease tend to be younger and survive longer than those with high-grade ovarian cancer, but when their cancer persists or comes back, it almost always thwarts treatment. Between 2% and 4% of patients respond to chemotherapy.  Hormonal therapies do modestly better, with a 9% response rate.

In the clinical trial of the drug selumetinib published in the February edition of The Lancet Oncology, eight of 52 (15 percent) patients had a complete or objective partial response (tumor shrinkage) and 34 (65 percent) had no disease progression during the two-year course of the study.

"These are remarkably encouraging results for what can ultimately be a devastating disease," says David Gershenson, M.D., professor in MD Anderson's Department of Gynecologic Oncology and Reproductive medicine, the paper's senior author.

Selumetinib hasn't made Doris Elliott's recurrent low-grade ovarian cancer disappear. But it shrank all of her tumors and has arrested their development for five years running. 

For Dotsy Elliott, cancer under control for five years and counting

After her diagnosis in 1997, six rounds of chemotherapy kept  cancer at bay until 2005. Surgery and nine rounds of chemotherapy did little to slow progression. Another clinical trial helped for about 18 months.

Patients with chronic myeloid leukemia (CML) or acute lymphoblastic leukemia that carries the Philadelphia chromosome (Ph+ALL) who can't tolerate the targeted drugs that revolutionized care for these leukemias now have three new options.

The U.S. Food and Drug Administration (FDA) has approved  three new drugs in the past few months. Ponatinib (Iclusig) was approved last week, an effective drug for many patients with  treatment-resistant disease. This comes on the heels of approvals of bosutinib (Bosulif) in September and omacetaxine (Synribo) in October.

Patients with both leukemias have enjoyed strong responses to imatinib (Gleevec) and second-generation drugs nilotinib (Tasigna) and dasatinib (Sprycel).  All work by inhibiting proteins called tyrosine kinases on leukemia cells, in particular the aberrant BCR-ABL protein that causes these diseases.

However, 30-40 percent of patients' CML resists imatinib. Nilotinib and dasatinib work for about 40-50 percent of those patients.

"It's important to have as many therapies against cancer as we can, because rarely does one drug or combination succeed for all patients," said Jorge Cortes, M.D., professor in MD Anderson's Department of Leukemia.  "These new drugs cover different gaps in treatment, so they can serve our patients in different ways."

By Leslie Loddeke, Publications Coordinator, Melanoma Medical Oncology Department

M.D. Anderson Melanoma Medical Oncology Chair Patrick Hwu, M.D., and Professor  Wen-Jen Hwu, M.D., Ph.D., were coauthors of one of the papers named in Nature Medicine's "Notable advances 2012" list of the year's top basic biomedical discoveries.

The article notes "certain areas of biomedicine saw fast-paced discovery this year" in presenting its list of "the papers that helped these fields advance quickly" in 2012.

Under the heading "Immunotherapy: Co-receptor clampdown," the article cited two papers that made the inhibitory co-receptor PD-1 (programmed cell death protein 1, found on T cells) "one of the darlings of the cancer immunotherapy field this year."

A team led by scientists from the Johns Hopkins School of Medicine reported the findings of a study of a PD-1-specific antibody in patients with different types of cancer in a New England Journal of Medicine article, as well as those from a companion study in a second article, "Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer."  

M.D. Anderson's two co-authors on the second study reflect the department's participation inthe clinical trial. Wen-Jen Hwu was principal investigator at the M.D. Anderson site. In that study, researchers reported that "of 207 patients with advanced cancer who received an anti-PDL1 antibody, 6-17% of evaluable patients experienced an objective response (either complete or  partial)," Nature Medicine noted.

Despite the fact that it remains unknown why only certain tumors and patients responded to the antibodies, "these trials further validate immune modulation of T cell activity as a therapeutic approach to cancer treatment," Nature Medicine concluded.

An international study of ibrutinib in people with relapsed or refractory mantle cell lymphoma (MCL) continues to show unprecedented and durable results with few side effects.

A researcher from The University of Texas MD Anderson Cancer Center presented interim findings of the multi-center Phase 2 study earlier this week at the 54th American Society of Hematology Annual Meeting and Exposition.

The MCL study was the third of the meeting presented by MD Anderson faculty about ibrutinib.  The others were in combination for chronic lymphocytic leukemia and by itself for relapsed or resistant follicular lymphoma.  

"I believe we are witnessing a breakthrough in mantle cell lymphoma. This is great news for patients," said Michael Wang, M.D., associate professor in MD Anderson's Departments of Lymphoma and Myeloma and Stem Cell Transplantation and Cellular Therapy. Wang is lead author of the study.

Wang, director of the mantle cell lymphoma (MCL) program at MD Anderson, has spent the past 12 years researching the disease, including clinical trials of proteasome inhibitors, immune-modulating agents and an mTOR inhibitor.

"In a heavily treated relapsed or refractory population, oral ibrutinib induced a response rate as high as 70% - better than any other single agent ever tested in MCL," he said. "The response is durable with a long progression-free survival."

A new technique for expanding blood stem cells from umbilical cords in the lab before transplanting them into a patient reduces the perilous time it takes for the new blood supply to take hold.

Cord blood transplants provide a source of blood stem cells to cancer patients who need a transplant after high-dose chemotherapy for leukemia, lymphoma and other malignancies but cannot find a matched donor. 

This is particularly true for people of Latino, African or Asian heritage, who are underrepresented in the bone marrow donor pool, which makes it hard to find a matched blood stem cell donor.

"Pre-transplant cord blood expansion on mesenchymal precursor cells could become the new standard of care if our findings are confirmed in a randomized clinical trial," said Elizabeth Shpall, M.D., professor in the Department of Stem Cell Transplantation and Cellular Therapy.  She is principal investigator of an early stage clinical trial and senior author of a paper published this week in the New England Journal of Medicine.

Umbilical cords provide a much lower dose of cells than those given by a matched donor whose stem cells are taken from the bone marrow or circulating blood. The result: slower establishment of the new blood supply, particularly white cells (neutrophils) and platelets, exposing patients to greater risk of infection and bleeding.

Shpall and colleagues show how expanding one of the two cords on a bed of supportive  in the lab increases the number of cells transplanted and the speed of establishment (engraftment) of white cells and platelets for the patient over those who get the usual unexpanded double cord transplant. 

 

A drug approved for treating resistant versions of two types of lymphoma knocked down the disease in all 26 patients evaluated in a phase I clinical trial of front line use combined with chemotherapy.

Michelle Fanale, M.D., assistant professor in MD Anderson's Department of  Lymphoma and Myeloma presented results of the trial at the 54th American Society of Hematology Annual Meeting and Exposition in Atlanta.

The trial provides evidence that the drug brentuximab vedotin (ADCETRIS, developed by Seattle Genetics, Inc.) potentially could be brought forward to front line treatment and could be used to treat additional types of non-Hodgkin lymphoma.

A combination of brentuximab vedotin with a chemotherapy combination called CHP produced complete remissions in 23 of the 26 patients, who had either systemic anaplastic large cell lymphoma (19 patients)  or a CD30-positive mature T cell or natural killer cell lymphoma (seven patients).  The other three had partial remissions.

All seven of the mature T cell or natural killer cell lymphoma patients had a complete remission.

Updated: 4:30 p.m. Friday, Dec. 14

The U.S. Food and Drug Administration approved ponatinib (Iclusig) for chronic myeloid leukemia and Philadelphia chromsome-positive acute lymphoblastic leukemia today.

Approval under the agency's accelerated review process occurred three months ahead of the deadline for FDA response.

Data from the phase 2 pivotal clinical trial provided the basis for approval.

"The availability of ponatinib will drastically improve the outcome of most patients with CML and Philadelphia-positive ALL who are resistant or intolerant to prior tyrosine kinase inhibitor therapy.  It is a safe and effective therapy that meets an unmet medical need and has to date overcome all known resistant mutations in preclinical studies" said Jorge Cortes, M.D., professor and deputy chair, in The University of Texas M.D. Anderson Cancer Center Department of Leukemia Friday.

Cortes led all clinical trials of Iclusig, the drug's new commercial name, developed by Ariad Pharmaceuticals of Cambridge, Mass. 

Resume original post

Sunday began with a news briefing about a promising phase II trial for ponatinib, a chronic myeloid leukemia investigational drug that  helps patients who are resistant to existing CML drugs.

Jorge Cortes, M.D., professor in the Department of Leukemia, presented the phase II data at the 54th American Society of Hematology Annual Meeting and Exposition  less than two weeks after the phase I results were published in the New England Journal of Medicine.

The new, larger trial also shows ponatinib sparks responses in patients with the T315I mutation and other drug-resistant mutations.

T315I is present in up to 20 percent of patients and blocks the docking station where three other successful CML drugs (Gleevec, Sprycel and Tasigna)  normally connect to the mutant protein. Patients in the trial have had at least two of these drugs fail.

At 15.3 months of median follow up for patients in the initial, chronic phase of CML, 149 or 267 (54%) had a major cytogenetic response (reduction of CML cells in the blood) and 46% had a complete cytogenetic response (no CML cells in the bone marrow).

Of 64 chronic phase CML patients with the T315I mutation, 45 (70%) achieved major cytogenetic response with 66% reaching complete cytogenetic response.

Elnar Koseoglu of Physician Relations and Bradley Swinney of Banner MD Anderson await the afternoon rush at booth 3500 in the exhibition hall at the 54th ASH Annual  Meeting and Exposition.

Occupying prime corner real estate right by a pizza parlor in the massive hall, the MD Anderson Physican Relations   booth had 225 physician visitors by early afternoon. With scientists and physicians in lectures and seminars most of the day, traffic is feast (during breaks) or famine.

MD Anderson faculty are always a major, influential presence at ASH, the world's premier meeting about the science and diseases of the blood.

New drugs could spell end of chemo for chronic lymphocytic leukemia

Jan Burger, M.D., associate professor in the Department of Leukemia, spoke at the meeting's first news briefing for journalists early Saturday.

His clinical trial of the drug ibrutinib combined with rituximab (Rituxan) for high-risk CLL patients with resistant disease attracted attention because 38 of 40 patients were still on the drug and in remission at four months.Side effects have been mild.

"Although this study has a short follow-up time so far, we're encouraged that the vast majority of patients are responding and can continue treatment," Burger said. "We still need long-term follow up to see if the remissions are durable and the low toxicity endures." 

The high-risk patients in the clinical trial are essentially out of treatment options.   

Rituximab is thought to block a resistance mechanism to ibrutinib. Earlier and ongoing clinical studies by MD Anderson and other research teams indicate ibrutinib alone is highly effective for patients with lower risk disease.  

Chemotherapy combinations are curative for most CLL patients, but the harsh treatment can lead to lethal secondary cancers for some.

For more details, see the MD Anderson news release about the study and the ASH study abstract (click OK at the opening page and you'll get to the abstract.) CLL is one of the eight cancers targeted by MD Anderson's  Moon Shots Program.

Burger presents his findings to other scientists and physicians Sunday afternoon. 

By David M. Gershenson, M.D.

The Holy Grail of oncology is personalized cancer therapy. While patients with either malignant ovarian germ cell tumors or ovarian sex cord-stromal tumors, constituting two of the three major categories of ovarian cancer, have historically been treated on separate clinical trials, women with all types of epithelial tumors have been treated identically on the same trials over the past several decades.

With the explosion of information related to the molecular biology of ovarian cancer coupled with technological advances, continuing to study these epithelial cancers as a single disease entity is no longer acceptable.

In 2005, the Gynecologic Oncology Group (GOG), a National Cancer Institute - sponsored cooperative group, established the Rare Tumor Committee. The formation of this committee provided the impetus to begin to develop separate trials for women with three rare epithelial ovarian subtypes--clear cell carcinoma, low-grade serous carcinoma, and mucinous carcinoma.

An experimental drug targeting a common mutation in melanoma successfully shrank tumors that spread to the brain in nine out of 10 patients in part of an international phase I clinical trial reported in the May 18 issue of The Lancet.

The drug dabrafenib, which targets the Val600 BRAF mutation that is active in half of melanoma cases, also cut the size of tumors in 25 of 36 patients with late-stage melanoma that had not spread to the brain. The drug also showed activity in other cancer types with the BRAF mutation.

"Nine out of 10 responses among patients with brain metastases is really exciting. No other systemic therapy has ever demonstrated this much activity against melanoma brain metastases," said study co-lead author Gerald Falchook, M.D., assistant professor in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center.

Melanoma patients whose disease has spread to their brains have a median overall survival of four or five months from the time of diagnosis, the researchers note.  Drugs used to treat brain metastases have response rates of 10 percent or lower. Surgery and stereotactic or whole-brain radiation also are used.

Tumor shrinkage in the nine responders ranged from 20 percent to 100 percent. In four cases, the brain metastases disappeared.