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GVAX vs. Placebo for MDS/AML After Allo HSCT

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01773395
Recruitment Status : Recruiting
First Posted : January 23, 2013
Last Update Posted : July 23, 2019
Sponsor:
Collaborators:
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Information provided by (Responsible Party):
Vincent T. Ho, MD, Dana-Farber Cancer Institute

Brief Summary:

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, CMML, 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), Chronic Myelomonocytic Leukemia (CMML), 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/CMML/AML. Allogeneic stem cell transplantation is a standard treatment for MDS/CMML/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/CMML/AML cells in your body. This is also known as the "graft-versus-leukemia" or "GVL" effect. In patients with advanced MDS, CMML, 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 or disease Intervention/treatment Phase
Myelodysplastic Syndrome Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia Biological: GVAX Biological: Placebo Vaccine Procedure: Allogeneic Hematopoietic Stem Cell Transplant Drug: Busulfan Drug: Fludarabine Drug: Tacrolimus Drug: Methotrexate Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 152 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, 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
Study Start Date : January 8, 2013
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : January 2033


Arm Intervention/treatment
Active Comparator: GVAX

GVAX vaccine

Participants in the GVAX vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD. GVAX arm participants meeting criteria to begin vaccinations will be administered the GVAX vaccine at established study time points.

Biological: GVAX
GVAX or placebo vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria. Only participants in the GVAX arm will receive GVAX vaccine.

Procedure: Allogeneic Hematopoietic Stem Cell Transplant
Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor. This is given as a transfusion through a central intravenous line (IV usually placed in the chest or arm).

Drug: Busulfan
In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 5 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.

Drug: Fludarabine
In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 5 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.

Drug: Tacrolimus

Just prior to and immediately following the infusion of stem cells, the participant will receive medications to help prevent graft-versus-host disease (GVHD), a common complication of transplant where the donor's immune cells attack the recipient's body. The medications the participant will receive to prevent GVHD will include:

  • Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
  • Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.

Drug: Methotrexate

Just prior to and immediately following the infusion of stem cells, the participant will receive medications to help prevent graft-versus-host disease (GVHD), a common complication of transplant where the donor's immune cells attack the recipient's body. The medications the participant will receive to prevent GVHD will include:

  • Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
  • Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.

Placebo Comparator: Placebo

Placebo vaccine

Participants in the Placebo vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD. Placebo vaccine arm participants meeting criteria to begin vaccinations will be administered the placebo vaccine at established study time points.

Biological: Placebo Vaccine
GVAX or placebo vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria. Only participants in the placebo arm will receive placebo vaccine.

Procedure: Allogeneic Hematopoietic Stem Cell Transplant
Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor. This is given as a transfusion through a central intravenous line (IV usually placed in the chest or arm).

Drug: Busulfan
In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 5 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.

Drug: Fludarabine
In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 5 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.

Drug: Tacrolimus

Just prior to and immediately following the infusion of stem cells, the participant will receive medications to help prevent graft-versus-host disease (GVHD), a common complication of transplant where the donor's immune cells attack the recipient's body. The medications the participant will receive to prevent GVHD will include:

  • Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
  • Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.

Drug: Methotrexate

Just prior to and immediately following the infusion of stem cells, the participant will receive medications to help prevent graft-versus-host disease (GVHD), a common complication of transplant where the donor's immune cells attack the recipient's body. The medications the participant will receive to prevent GVHD will include:

  • Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
  • Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.




Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 18 months ]
    Progression-Free Survival (PFS) at 18 months after randomization


Secondary Outcome Measures :
  1. 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 ]
    Assessment of the safety of vaccination following allogeneic (ablative or reduced intensity) stem cell transplantation

  2. Incidence of acute and chronic GVHD [ Time Frame: 2 years ]
    Assessment of incidence fof grade 2-4 and grade 3-4 acute GVHD, and chronic GVHD after vaccination following allogeneic stem cell transplantation

  3. PFS after start of vaccination [ Time Frame: 2 years ]
    Assessment of PFS after start of vaccination

  4. Relapse and non-relapse mortality [ Time Frame: 2 years ]
    Assessment of relapse and non-relapse mortality after vaccination

  5. Overall Survival [ Time Frame: 2 years ]
    Assessment of overall survival after vaccination

  6. Biologic activity of GVAX vs. Placebo as assessed by laboratory and histologic analyses of blood before and after vaccination. [ Time Frame: 2 years ]
    Assessment of the biologic activity of GVAX as compared to placebo vaccination after HSCT



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01773395


Contacts
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Contact: Vincent Ho, MD 6176325938 vtho@partners.org

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Yi-Bin Chen, MD    617-726-5765    YCHEN6@partners.org   
Principal Investigator: Yi-Bin Chen, MD         
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Vincent Ho, MD    617-632-5938    vtho@partners.org   
Principal Investigator: Vincent Ho, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Vincent Ho, MD    617-632-5938    vtho@partners.org   
Principal Investigator: Vincent Ho, MD         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Jacalyn Rosenblatt, MD    617-667-9920    jrosenb1@bidmc.harvard.edu   
Principal Investigator: Jacalyn Rosenblatt, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Investigators
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Principal Investigator: Vincent Ho, MD Dana-Farber Cancer Institute

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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
First Posted: January 23, 2013    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019
Keywords provided by Vincent T. Ho, MD, Dana-Farber Cancer Institute:
Advanced
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Myelodysplastic-Myeloproliferative Diseases
Vidarabine
Methotrexate
Fludarabine phosphate
Fludarabine
Busulfan
Vaccines
Tacrolimus
Immunologic Factors
Physiological Effects of Drugs
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents