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Clinical Trials Monthly - July/August 2012

Clinical Trials Monthly presents new and important trials that may benefit your patients. This month we’ve included trials for a new bone marrow transplant trial, and studies for bladder, breast, and ovarian cancer, as well as lymphoma.

This Month’s Featured Clinical Studies

Crohn's Disease

  • New trial tests transplantation to cure Crohn’s (NCT01570348)

Hematologic Malignancies

  • Double Cord Versus Haploidentical Transplants (NCT01597778)

Bladder Cancer

  • Ramucirumab or IMC-18F1 with Docetaxel or Docetaxel Alone for Bladder, Urethra, Ureter, or Renal Pelvis Carcinoma (NCT01282463)

Breast Cancer

  • Phase II Topical Imiquimod/Abraxane for Breast Cancer (NCT00821964 )

Lymphoma

  • CAL-101 for Relapsed or Refractory Hodgkin’s Lymphoma (NCT01393106)
  • CAL-101 for Indolent B-Cell Non-Hodgkin’s Lymphoma (NCT01282424)
  • Rituximab + Lenalidomide vs Chemotherapy (RELEVANCE-7636) for Follicular Lymphoma (NCT01476787)

Ovarian Cancer

  • Vaccine Therapy for Stage III-IV Ovarian Cancer (NCT01322802)

 

Crohn's Disease

 

New trial tests transplantation to cure Crohn’s

By Dean Forbes

A new clinical trial testing bone marrow transplantation to cure severe cases of Crohn’s disease may provide a new treatment option to those who suffer from the chronic inflammatory condition of the gastrointestinal tract.

Dr. George McDonald, a transplant researcher and gastroenterologist at Fred Hutchinson Cancer Research Center’s Clinical Research Division, leads the study.

The initial goal of the Crohn’s Allogeneic Transplant Study (CATS) is to treat a small number of patients with treatment-resistant Crohn’s disease by transplanting matched bone marrow cells from a sibling or unrelated donor. The transplant replaces a diseased or abnormal immune system with a healthy one.

The idea of swapping out the immune system is based on evidence that Crohn’s is related to an abnormal immune response to intestinal bacteria and a loss of immune tolerance. There is strong evidence that genetic abnormalities in the immune regulatory system are linked to the disease, McDonald said. Although the CATS clinical trial represents a new direction for bone marrow transplantation, the procedure has precedent. The Hutchinson Center has used allogeneic transplants to cure patients who suffered from both leukemia and Crohn’s, with subsequent disappearance of the signs and symptoms of Crohn’s. Similar experiences have been reported from studies done in Germany.

While autologous stem cell transplants — in which the patient’s own hematopoietic cells are removed and then returned after high-dose chemotherapy is given to suppress the immune system — have been used to treat Crohn’s patients, the benefits have not always been permanent, probably because the risk genes for Crohn’s are still present.

Crohn’s disease is usually discovered in adolescents and young adults but can occur from early childhood to older age. The incidence of Crohn’s disease varies in different parts of the world with rates of four to nine persons per 100,000 people in North America. According to the Crohn’s and Colitis Foundation of America, a leading advocacy organization, Crohn’s may affect more than 700,000 Americans. Of those affected by Crohn’s, about 10 percent suffer from the most severe form for which no treatment is completely effective.

“The burden of this disease lays heavily on those who don’t respond to any therapy,” McDonald said.

More information about the study and a link to a patient-eligibility questionnaire can be found online at www.seattlecca.org/clinical-trials/transplant-NCT01570348.cfm.

The CATS investigator team includes transplant physicians, gastroenterologists, pathologists and nurses from the Hutchinson Center, University of Washington, Seattle Children’s and the Benaroya Research Institute. The bone marrow transplant procedures will be conducted at Seattle Cancer Care Alliance, the University of Washington Medical Center, and Seattle Children’s Hospital.
 

Hematologic Malignancies

A Multi-Center, Phase III, Randomized Trial of Reduced Intensity (RIC) Conditioning and Transplantation of Double Unrelated Umbilical Cord Blood (dUCB) Versus HLA-Haploidentical Related Bone Marrow (Haplo-BM) for Patients with Hematologic Malignancies (NCT01597778)

Now recruiting for acute lymphocytic leukemia, acute myelogenous leukemia, Burkitt’s lymphoma, follicular lymphoma, Hodgkin’s lymphoma, and mantle cell lymphoma, this multicenter trial will randomize patients between two alternative donor stem cell protocols: haploidentical (HLA-mismatched) family members (including parents, children, and about half of a patient’s siblings) versus unrelated umbilical cord blood.  This study is being coordinated nationwide by the Blood and Marrow Transplant Clinical Trial Network.

In some cases, patients of mixed ethnic heritage can have the most difficulty finding matches, and may benefit the most from these studies. “Patients who may not have had a chance at a matched donor transplant will have more opportunities through the growth of these alternative donor options,” says SCCA’s Paul V. O’Donnell, MD, PhD, one of three principal investigators in this study. The trial will be open for four years and patients will be followed for three years after their transplant.

Investigator: Paul V. O’Donnell, MD, PhD
 

Bladder Cancer

An Open-Label, Multicenter, Randomized Phase II Study Evaluating the Safety and Efficacy of Docetaxel in Combination with Ramucirumab (IMC-1121B) Drug Product or IMC-18F1 or without Investigational Therapy as Second-line Therapy in Patients with Locally Advanced or Metastatic Transitional Cell Carcinoma of the Bladder, Urethra, Ureter, or Renal Pelvis Following Disease Progression on First-line Platinum-based Therapy (NCT01282463.cfm)

This multi-center trial will enroll participants with metastatic transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis who have had disease progression on first-line platinumbased chemotherapy regimens.

Participants will be enrolled into one of three treatment arms as the purpose of this study is to find out if treatment with gemcitabine, cisplatin, and the study drug (OGX-427) at two different doses (600 mg and 1000 mg) can increase survival in subjects with TCC compared to gemcitabine, cisplatin, and placebo. The study will also see if OGX-427 at two different dose levels is safe when given with gemcitabine and cisplatin. OGX-427 has been tested alone in 42 subjects and in combination with docetaxel in 22 patients.

Investigator: Evan Ya-Wen Yu, MD

 

Breast Cancer

 

Phase II Study of Topical Imiquimod (Aldara) and Weekly Abraxane for the Treatment of Breast Cancer Cutaneous Metastases (NCT00821964)

This phase II trial is studying the side effects of giving topical imiquimod together with Abraxane (paclitaxel albumin-stabilized nanoparticle formulation) to see how well it works in treating patients with advanced breast cancer.

Biological therapies, such as imiquimod, may stimulate the immune system to kill tumor cells. Drugs used in chemotherapy, such as Abraxane, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imiquimod together with Abraxane may kill more tumor cells.

The purpose of this study is to evaluate the safety and effects, good or bad, of the drugs imiquimod and Abraxane® as treatment for advanced breast cancer with chest wall and/or skin metastases. The combined use of Abraxane® and imiquimod in this study is experimental.

Open to patients with male breast cancer, recurrent breast cancer, skin metastases, stage IV breast cancer.

Investigator: Lupe G. Salazar, MD

 

Lymphoma

A Phase II Study to Assess the Efficacy and Safety of CAL-101 in Patients with Indolent B-Cell Non-Hodgkin’s Lymphoma Refractory to Rituximab and Alkylating Agents (NCT01282424)

The purpose of this study is to evaluate the efficacy and safety of CAL-101 (GS-1101) in patients with previously treated, indolent (slow-growing) non-Hodgkin’s lymphoma (iNHL) that is resistant to rituximab and alkylating-agent chemotherapy.

The primary objective will be to assess the overall response rate. CAL-101 is a potent, selective inhibitor of a type of phosphatidylinositol 3 kinase (PI3K) enzyme that is implicated in cancer and inflammatory diseases.

In the Phase I trial of this drug, CAL-101 was well tolerated with no dose-limiting toxicity in any of the patients. CAL-101 decreases cellular proliferation and/or cell death in a range of non-Hodgkin’s lymphoma cell lines.

Eligible patients will be older than 18 years of age and have histologically confirmed B-cell iNHL. Treatment with CAL-101 can continue in responding patients as long as the study is ongoing and the patients have no excess toxicity from treatment.

Investigator: Ajay K. Gopal, MD
 

A Phase II Study to Assess the Efficacy and Safety of CAL-101 in Patients with Indolent B-Cell Non-Hodgkin’s Lymphoma Refractory to Rituximab and Alkylating Agents (NCT01282424)

The purpose of this study is to evaluate the efficacy and safety of CAL-101 (GS-1101) in patients with previously treated, indolent (slow-growing) non-Hodgkin’s lymphoma (iNHL) that is resistant to rituximab and alkylating-agent chemotherapy.

The primary objective will be to assess the overall response rate. CAL-101 is a potent, selective inhibitor of a type of phosphatidylinositol 3 kinase (PI3K) enzyme that is implicated in cancer and inflammatory diseases.

In the Phase I trial of this drug, CAL-101 was well tolerated with no dose-limiting toxicity in any of the patients. CAL-101 decreases cellular proliferation and/or cell death in a range of non-Hodgkin’s lymphoma cell lines.

Eligible patients will be older than 18 years of age and have histologically confirmed B-cell iNHL. Treatment with CAL-101 can continue in responding patients as long as the study is ongoing and the patients have no excess toxicity from treatment.

Investigator: Ajay K. Gopal, MD
 

A Phase III Open-Label Randomized Study to Compare the Efficacy and Safety of Rituximab Plus Lenalidomide (CC-5013) Versus Rituximab Plus Chemotherapy Followed by Rituximab in Subjects with Previously Untreated Follicular Lymphoma. The “RELEVANCE” Trial (Rituximab Lenalidomide Versus any Chemotherapy) (NCT01476787)

A new international, randomized study at SCCA, the RELEVANCE trial hopes to provide a better treatment for newly diagnosed follicular lymphoma patients. This trial will help determine whether a new combination of approved drugs, lenalidomide and rituximab, neither of which are chemotherapies, is more effective than the standard of care. “We are looking for high response rates and longer response rates,” says Edward N. Libby, MD, lead investigator on the RELEVANCE trial at SCCA.

Unique to this study is lenalidomide (Revlimid), which has been added in for maintenance – small doses over long periods of time. “Revlimid affects the immune system in ways to help kill cancer, but we don’t know exactly how this works,” Libby says. Revlimid is currently used to treat multiple myeloma and myelodysplasia. Both of the study drugs have been approved for treatment in other diseases. Patients gaining control of their disease will have rituximab every three weeks and lenalidomide three out of four weeks until which time maintenance therapy can begin.

Investigator: Edward N. Libby, MD
 

Ovarian Cancer

A Phase I Trial of the Safety and Immunogenicity of a DNA Plasmid Based Vaccine Encoding the Amino Acids 1-163 of Insulin-Like Growth Factor Binding Protein-2 (IGFBP-2) in Patients with Advanced Ovarian Cancer (NCT01322802)

This Phase I trial is studying the side effects of vaccine therapy in treating patients with stage III-IV ovarian cancer. IGFBP-2 is a protein found in the blood and tumor cells of most women who have been diagnosed with ovarian cancer. High levels of IGFBP-2 have been associated with more invasive disease. One strategy for reducing IGFBP-2 on tumor cells is to generate an immune response against the tumor cells expressing IGFBP-2.

Immunizing patients with a vaccine against IGFBP-2 may do this. The vaccine is made up of DNA isolated from a bacteria into which a portion of the IGFBP-2 protein code (DNA) is inserted. In this trial, we are studying the safety of the vaccine (monthly intradermal injections for three months). In addition, we will measure immune response to help determine how effective the vaccine is in stimulating the immune system to recognize IGFBP-2.

Patients with advanced stage ovarian cancer (stages III or IV) who have been treated to complete remission with standard therapies may be eligible for this trial.

Investigator: Mary (Nora) L. Disis, MD


Adult Bone Marrow Transplant News

The SCCA Adult Bone Marrow Transplant News is a publication presenting the latest information on bone marrow transplant research at SCCA, providing up-to-date information for all health care professionals caring for transplant patients.

Pediatric Bone Marrow Transplant News

Read about important outcomes research at the Fred Hutch that may benefit your patients.

Clinical Trials Monthly

Each issue of Clinical Trials Monthly highlights several of the more than 200 clinical trials that are currently recruiting patients at SCCA.

The Leading Edge Newsletter

Each quarterly Leading Edge newsletter will highlight a new topic to give you the latest news on leading-edge therapies that SCCA physicians are offering.