GVAX vs. Placebo for MDS/AML After Allo HSCT

NCT01773395 | Terminated Phase 2 Results DMC

• 1 other identifier: 12-217
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 4

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 MDS, CMML, or AML from relapsing after 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 these types of cancer. Participants are being asked to participate in this trial because they have advanced myelodysplastic syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML), or acute myeloid leukemia (AML). Investigators have determined that participants are a candidate for an allogeneic stem cell transplant as treatment for MDS/CMML/AML. Allogeneic stem cell transplantation is a standard treatment for MDS/CMML/AML. It can be effective because the cells from the donor (also known as the graft) could form a new immune system that can fight against the MDS/CMML/AML cells in the 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, 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 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. Participants in this study will be "randomized" to receive either GVAX vaccination or placebo (a saline solution) vaccination. Randomization means participants are put into a group by chance. It is like flipping a coin. There is a 50% chance they will receive the GVAX vaccine and a 50% chance they will receive placebo. Neither participants nor investigators will know which participants 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.

Conditions

Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Acute Myeloid Leukemia

Keywords

Advanced

Outcome Measures

Primary Outcomes (1)

• 18-Month Progression Free Survival

  Progression-Free Survival (PFS) at 18 months after randomization. Progression-free survival is defined as time from randomization to progression of disease or death whichever occurs first. Patients with relapse/progressive disease who re-enter remission after vaccination or upon withdrawal of immune suppression alone will not be considered as having disease progression. The primary analysis will be performed using the modified intention-to-treat (ITT) principle, i.e., all transplanted and eligible patients who receive at least one vaccination will be included in the analysis according to the treatment arm they are randomized to. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free. Progression is defined by either morphological evidence of acute leukemia or MDS consistent with pre-transplant features is defined by either morphological evidence of acute leukemia or MDS consistent with pre-transplant features

  18 months

Secondary Outcomes (4)

• Percentage of Participants Experiencing Grade 3 or Higher Non-Hematologic or Grade 4 or Higher Hematologic Adverse Events

  18 Months

• Percentage of Participants Experiencing Acute and Chronic Graft-Versus-Host Disease

  1 and 3 years

• Percentage of Participants With Relapse and/or Non-Relapse Mortality

  18 Months

• 18-Month Overall Survival

  18 Month

Study Arms (2)

GVAX

ACTIVE COMPARATOR

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; Procedure: Allogeneic Hematopoietic Stem Cell Transplant; Drug: Busulfan; Drug: Fludarabine; Drug: Tacrolimus; Drug: Methotrexate

Placebo

PLACEBO COMPARATOR

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; Procedure: Allogeneic Hematopoietic Stem Cell Transplant; Drug: Busulfan; Drug: Fludarabine; Drug: Tacrolimus; Drug: Methotrexate

Interventions

GVAX BIOLOGICAL

GVAX or placebo vaccination will begin between 30 to 60 days following participant's transplant, provided participant meets vaccination initiation criteria. Only participants in the GVAX arm will receive GVAX vaccine.

GVAX

Placebo Vaccine BIOLOGICAL

GVAX or placebo vaccination will begin between 30 to 60 days following participant's transplant, provided participant meets vaccination initiation criteria. Only participants in the placebo arm will receive placebo vaccine.

Placebo

Allogeneic Hematopoietic Stem Cell Transplant PROCEDURE

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).

GVAX; Placebo

Busulfan DRUG

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.

GVAX; Placebo

Fludarabine DRUG

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.

GVAX; Placebo

Tacrolimus DRUG

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.

GVAX; Placebo

Methotrexate DRUG

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.

GVAX; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Massachusetts General Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Ho VT, Kim HT, Brock J, Galinsky I, Daley H, Reynolds C, Weber A, Pozdnyakova O, Severgnini M, Nikiforow S, Cutler C, Koreth J, Alyea EP, Antin JH, Gooptu M, Romee R, Shapiro R, Chen YB, Rosenblatt J, Avigan D, Hodi FS, Dranoff G, Wu CJ, Ritz J, Soiffer RJ. GM-CSF secreting leukemia cell vaccination for MDS/AML after allogeneic HSCT: a randomized, double-blinded, phase 2 trial. Blood Adv. 2022 Apr 12;6(7):2183-2194. doi: 10.1182/bloodadvances.2021006255.

  PMID: 34807983 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic

Interventions

Busulfan; fludarabine; Tacrolimus; Methotrexate

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Macrolides; Lactones; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Vincent Ho
• Organization: Dana-Farber Cancer Institute

Vincent_Ho@dfci.harvard.edu

617-632-5938

Study Officials

• Vincent Ho, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 8, 2013
• First Posted: January 23, 2013
• Study Start: January 8, 2013
• Primary Completion: December 11, 2020
• Study Completion: November 24, 2021
• Last Updated: July 18, 2022
• Results First Posted: March 18, 2022

Record last verified: 2022-06

Locations

US (4)