Vaccine Therapy after Donor Stem Cell Transplant in Treating Patients with Advanced Myelodysplastic Syndrome or Acute Myeloid Leukemia
- Acute myeloid leukemia (AML), myelodysplastic syndrome (MDS)-refractory anemia with excess blasts (RAEB) (including chronic myelomonocytic leukemia [CMML] with excess blasts and MDS/myeloproliferative neoplasm [MPN] overlap syndrome) not in remission (defined as >= 5% blast in bone marrow or peripheral blood) prior to leukemia cell harvest; patients may receive additional cytoreductive therapy after leukemia cell harvest and before admission for transplant, at the discretion of the treating physician; for patients with MDS-EB1 (< 10% blasts) or CMML-1, it is recommended that they proceed directly to transplant after the harvest if donor is available; if there is an extended delay, interval therapy with HMA is allowed * Patients may or may not have active disease at the time of transplant conditioning, but for reduced intensity conditioning (RIC) candidates, it is strongly recommended that disease is cytoreduced such that the pre-transplant admission marrow shows: ** < 30% blasts in a normocellular marrow (>= 50% cellularity), or ** < 50% blasts in a hypocellular marrow (< 50% cellularity)
- Human leukocyte antigen (HLA) 8/8 or 7/8 matched related or unrelated donor available, as determined by antigen or allele level typing at HLA A, B, C, and allele level typing at major histocompatibility complex, class II, DR beta 1 (HLA DRB1)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Patient deemed to be suitable candidate for myeloablative or reduced intensity conditioning allogeneic HSCT using PBSC or marrow as stem cell source
- Total bilirubin =< 2.0 mg/dL; in patients with Gilbert’s syndrome, total bilirubin >= 2.0 is permitted
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
- Serum creatinine =< 2.0 mg/dL
- The effects of GVAX on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
- Leukemia with active central nervous system (CNS) involvement
- Positive human immunodeficiency virus (HIV) or human T-cell lymphotrophic virus (HTLV)-1 serology
- Participants may not be receiving any other non-Food and Drug Administration (FDA) approved study agents at the start of conditioning for stem cell transplantation; patients may receive non-FDA approved agents at the time of screening/enrollment as long as such agent(s) will be discontinued by the start of conditioning for transplantation
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to GM-CSF
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because pregnancy is an exclusion for chemotherapy and stem cell transplantation
- Individuals with a history of a different malignancy are ineligible except for the following circumstances: individuals with a history of other malignancies are eligible if they have been disease-free for at least 2 years; individuals with the following cancers are eligible if diagnosed and treated within the past 2 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
- Prior allogeneic transplant
I. Progression-free survival (PFS) at 18 months after randomization.
I. To assess the safety of vaccination following allogeneic (ablative or reduced intensity) stem cell transplantation.
II. To assess incidence of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD), and chronic GVHD after vaccination following allogeneic stem cell transplantation.
III. To assess PFS after start of vaccination.
IV. To assess relapse and non-relapse mortality after vaccination.
V. To assess overall survival after vaccination.
VI. To assess biologic activity of irradiated, adenovirus vector transfected GM-CSF secreting autologous leukemia cell vaccination (GVAX) (autologous sargramostim [GM-CSF]-secreting lethally irradiated leukemia cell vaccine) as compared to placebo vaccination after hematopoietic stem cell transplantation (HSCT).
OUTLINE: Patients are randomized to 1 of 2 arms. Patients may receive cytoreductive therapy between harvest and transplant conditioning, at the discretion of the treating doctor.
CONDITIONING: All patients receive either reduced-intensity conditioning comprising fludarabine phosphate intravenously (IV) over 1 hour once daily (QD) and low-dose busulfan IV twice daily (BID) on days -5 to -2 (FluBu2) OR myeloablative conditioning comprising fludarabine phosphate IV over 1 hour QD and busulfan IV 4 times a day (QID) on days -5 to -2 (Flu/Bu4).
TRANSPLANT: All patients undergo donor peripheral blood stem cell (PBSC) or bone marrow (BM) transplant on day 0.
GVHD PROPHYLAXIS: All patients receive tacrolimus orally (PO) BID starting on day –3 and continuing with taper one week after last vaccination for up to 9 months, and methotrexate IV on days 1, 3, 6, and 11.
ARM A: Within 30-45 days post-transplant, patients receive autologous GM-CSF-secreting lethally irradiated leukemia cell vaccine subcutaneously (SC) and intradermally (ID) weekly for 3 weeks and then every 2 weeks for 6 weeks for a total of 6 vaccinations.
ARM B: Within 30-45 days post-transplant, patients receive placebo vaccine SC and ID weekly for 3 weeks and then every 2 weeks for 6 weeks for a total of 6 vaccinations.
After completion of study treatment, patients are followed up for 15 years.
Trial Phase Phase II
Trial Type Treatment
Dana-Farber Harvard Cancer Center
Vincent Trien-Vinh Ho
- Primary ID 12-217
- Secondary IDs NCI-2013-00286
- Clinicaltrials.gov ID NCT01773395