GVAX vs. Placebo for MDS/AML After Allo HSCT

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Vincent T. Ho, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01773395
First received: January 8, 2013
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational intervention to learn whether the intervention, in this case, the GVAX vaccine, works in preventing your MDS or AML from relapsing after your allogeneic stem cell transplantation. "Investigational" means that the vaccine is still being studied and that research doctors are trying to find out more about it-such as the side effects it may cause, and if the vaccine is effective. It also means that the FDA has not yet approved the vaccine for your type of cancer.

You are being asked to participate in this trial because you have advanced myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Your doctor has determined that you are a candidate for an allogeneic stem cell transplant as treatment for your MDS/AML. Allogeneic stem cell transplantation is a standard treatment for MDS/AML. It can be effective because the cells from your donor (also known as the graft) could form a new immune system that can fight against the MDS/AML cells in your body. This is also known as the "graft-versus-leukemia" or "GVL" effect. In patients with advanced MDS or AML that is not in remission at the time of transplantation, as in your case, relapse remains the number one cause of transplant failure. As such, this clinical trial is designed to assess whether adding a leukemia vaccine early after transplantation could stimulate donor cells to fight your cancer and improve transplant outcomes.

In recent years, researchers at the Dana-Farber Cancer Institute have discovered that GVAX, a vaccine made from the patient's own cancer cells engineered to produce a protein called GM-CSF, can be effective in stimulating a powerful immune response specific to that cancer. GM-CSF is a naturally occurring hormone in the body that helps the immune system fight infections and diseases. The GVAX vaccine is made in the laboratory by using a virus (called adenovirus, which has been modified so it cannot cause illness) to insert the GM-CSF gene into tumor cells. The cells are then irradiated, which prevents them from being able to grow, before being administered to patients in a series of vaccinations.

A previous phase I clinical trial using this GVAX vaccine in patients with MDS/AML after allogeneic transplantation demonstrated that the GVAX vaccine is safe, and the survival outcomes were encouraging. The current randomized phase II study will investigate this vaccine further and gather more information to assess the activity.

If you participate in this research study, you will be "randomized" to receive either GVAX vaccination or placebo (a saline solution) vaccination. Randomization means that you are put into a group by chance. It is like flipping a coin. There is a 50% chance that you will receive the GVAX vaccine and a 50% chance you will receive placebo. Neither you nor your transplant doctor(s) will know which you will be receiving.

The primary goal of this trial is to assess if there will be a difference in the percentage of cancer free survivors in the vaccinated vs. placebo group at 18 months after transplant.


Condition Intervention Phase
Myelodysplastic Syndrome
Acute Myeloid Leukemia
Biological: GVAX
Biological: Placebo Vaccine
Procedure: Allogeneic Hematopoietic Stem Cell Transplant
Drug: Busulfan
Drug: Fludarabine
Drug: Tacrolimus
Drug: Methotrexate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Placebo-controlled Phase II Trial of Irradiated, Adenovirus Vector Transferred GM-CSF Secreting Autologous Leukemia Cell Vaccination (GVAX) Versus Placebo Vaccination in Patients With Advanced MDS/AML After Allogeneic Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Progression-Free Survival (PFS) at 18 months after randomization


Secondary Outcome Measures:
  • Safety and toxicity of vaccination, as measured by the development of grade II-IV and III-IV acute graft versus host disease, CTC grade 3 and higher non-hematologic toxicity, or grade 4 and higher hematologic toxicity attributable to vaccination [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Assessment of the safety of vaccination following allogeneic (ablative or reduced intensity) stem cell transplantation

  • Incidence of acute and chronic GVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assessment of incidence fof grade 2-4 and grade 3-4 acute GVHD, and chronic GVHD after vaccination following allogeneic stem cell transplantation

  • PFS after start of vaccination [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assessment of PFS after start of vaccination

  • Relapse and non-relapse mortality [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assessment of relapse and non-relapse mortality after vaccination

  • Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assessment of overall survival after vaccination

  • Biologic activity of GVAX vs. Placebo as assessed by laboratory and histologic analyses of blood before and after vaccination. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assessment of the biologic activity of GVAX as compared to placebo vaccination after HSCT


Estimated Enrollment: 152
Study Start Date: January 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: GVAX
GVAX vaccine
Biological: GVAX Procedure: Allogeneic Hematopoietic Stem Cell Transplant Drug: Busulfan Drug: Fludarabine Drug: Tacrolimus Drug: Methotrexate
Placebo Comparator: Placebo
Placebo vaccine
Biological: Placebo Vaccine Procedure: Allogeneic Hematopoietic Stem Cell Transplant Drug: Busulfan Drug: Fludarabine Drug: Tacrolimus Drug: Methotrexate

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • AML, MDS-RAEB not in remission prior to admission for transplant
  • HLA 8/8 or 7/8 matched related or unrelated donor available
  • Suitable candidate for myeloablative or reduced intensity conditioning allogeneic HSCT using PBSC or marrow as stem cell resource
  • ECOG performance status of 0-2
  • Normal organ function

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Leukemia with active CNS involvement
  • Positive HIV or HTLV-1 serology
  • History of allergic reactions to compounds of similar chemical or biologic composition to GM-CSF
  • Uncontrolled intercurrent illness
  • History of different malignancy except if disease free for at least two years or cervical cancer in situ, basal or squamous cell carcinoma of the skin diagnosed and treated within the past two years
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01773395

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Vincent Ho, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Vincent T. Ho, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01773395     History of Changes
Other Study ID Numbers: 12-217
Study First Received: January 8, 2013
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
Advanced

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014