Chemotherapy, Total Body Irradiation, and Post-Transplant Cyclophosphamide in Reducing Rates of Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant

  • STATUS
    Recruiting
  • End date
    Aug 9, 2025
  • participants needed
    33
  • sponsor
    Roswell Park Cancer Institute
Updated on 12 May 2022
radiation oncology
cancer
sirolimus
chronic myeloid leukemia
stem cell transplantation
graft versus host disease
myeloid leukemia
lymphoid leukemia
total body irradiation
fludarabine
hematologic malignancy
blast crisis
anemia
mycophenolate mofetil
cyclophosphamide
tyrosine
lymphoma
bone marrow transplant
multiple myeloma
hodgkin's disease
myeloproliferative disorder
white blood cell count
chronic myelomonocytic leukemia
carbon monoxide
ejection fraction
waldenstrom's macroglobulinemia
melphalan
karnofsky performance status
blood disorder
cell transplantation
leukemia
bone marrow procedure
hematologic disorder
transplant conditioning
white blood cells
chemotherapy regimen
allogeneic bone marrow transplantation
autograft
myelomonocytic leukemia
conditioning regimen
aplastic anemia
mycophenolate
allogeneic hematopoietic stem cell transplant
myeloproliferative neoplasm
myelodysplastic/myeloproliferative neoplasm

Summary

This phase Ib/2 trial studies how well chemotherapy, total body irradiation, and post-transplant cyclophosphamide work in reducing rates of graft versus host disease in patients with hematologic malignancies undergoing a donor stem cell transplant. Drugs used in the chemotherapy, such as fludarabine phosphate and melphalan hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft versus host disease). Giving cyclophosphamide after the transplant may stop this from happening.

Description

PRIMARY OBJECTIVES:

I. To determine the cumulative incidence of extensive chronic graft versus host disease (GVHD) at 1 year after transplantation utilizing the novel conditioning/GVHD prophylactic regimen for patients undergoing allogeneic hematopoietic cell transplantation, in patients who do not progress before day 100.

SECONDARY OBJECTIVES:

I. To evaluate clinical response, engraftment rate, progression-free survival (PFS) at one year and, overall survival (OS).

II. To determine the cumulative incidence of relapse. III. To evaluate the day 100 transplant-related mortality rate. IV. To determine the cumulative incidence of grade III-IV acute GVHD.

OUTLINE: This is a dose-escalation study of melphalan hydrochloride.

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo total body irradiation (TBI) on day -1.

STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.

GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and tacrolimus IV and then orally (PO) once tolerated on days 5-180 with a taper beginning on day 100.

After completion of study treatment, patients are followed up for 12 months and then annually thereafter.

Details
Condition Acute Myeloid Leukemia in Remission, Adult Acute Lymphoblastic Leukemia in Complete Remission, Chronic Myelogenous Leukemia, BCR-ABL1 Positive in Remission, Chronic Myelomonocytic Leukemia in Remission, Graft Versus Host Disease, Hodgkin Lymphoma, Minimal Residual Disease, Myelodysplastic Syndrome, Myeloproliferative Neoplasm, Non-Hodgkin Lymphoma, Plasma Cell Myeloma, Severe Aplastic Anemia, Waldenstrom Macroglobulinemia
Treatment cyclophosphamide, fludarabine phosphate, mycophenolate mofetil, laboratory biomarker analysis, allogeneic hematopoietic stem cell transplantation, Tacrolimus, Total-Body Irradiation, Sirolimus, Melphalan Hydrochloride
Clinical Study IdentifierNCT03192397
SponsorRoswell Park Cancer Institute
Last Modified on12 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

The patient must have a diagnosis of one of the following (one must be yes)
Acute myeloid leukemia (AML)
Acute lymphoblastic leukemia (ALL)
Chronic lymphoblastic leukemia (CLL)
Chronic myelogenous leukemia (CML) (chronic phase intolerant or unresponsive to tyrosine kinase inhibitors, accelerated phase, history of blast crisis)
Myelodysplastic syndrome (MDS)
Non-Hodgkin lymphoma (NHL)
Hodgkin lymphoma (HL) (received and failed frontline therapy or failed autologous transplantation or inability to collect enough peripheral blood stem cells [PBSC] for autologous hematopoietic cell transplant [auto-HCT])
Multiple myeloma (MM)
Severe aplastic anemia
Related donor matched 5/6 or better (A, B, DRB1)
Histocompatible donor identified
Unrelated donor matched 7/8 or better (A, B, C and DRB1)
Patients with severe aplastic anemia do not have disease requirements; however, if the
patient has a mismatched donor, the patient must have had prior therapy with
ATG
Patients with MDS/MPN only require <5% myeloblast on bone marrow evaluation
The following are eligible for study inclusion
Have a Karnofsky performance status score of > 50%
Patients with AML, ALL or CLL may be in CRi, patients with MM may be in VGPR
Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% predicted, corrected for hemoglobin and/or alveolar ventilation
Left ventricular ejection fraction > 40%
Patients with NHL/HL must be in CR
Bilirubin =< 3 x upper limit of normal
Liver alkaline phosphatase =< 3 x upper limit of normal
Serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit of normal
Calculated creatinine clearance > 40 cc/min by the modified Cockroft-Gault formula
Patient must be cleared pre-transplant by Radiation Oncology to be able to receive 400 cGy
Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
Patients who have failed a prior autologous or allogeneic transplant are eligible; however, at least 6 months must have elapsed between the start of this reduced intensity conditioning regimen and the last transplant if patient had a prior autologous or myeloablative allogeneic bone marrow transplant (BMT)
At least 2 weeks since prior radiation treatment and/or surgery. Appropriate washout of prior chemotherapy per BMT standard of care. If medication is not on the list, go by physician discretion
Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria

Moderate to severe myelofibrosis within 60 days prior to transplant
Presence of human leukocyte antigen (HLA) antibodies to the donor within 60 days prior to transplant
Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study intervention
Patients who in the opinion of the treating physician are unlikely to comply with the restrictions of allogeneic stem cell transplantation based on formal psychosocial screening. (i.e., serious, uncontrolled psychiatric illness/social situations that would limit compliance with study requirements)
Uncontrolled diabetes mellitus, cardiovascular disease, active serious infection or other condition which, in the opinion of treating physician, would make this protocol unreasonably hazardous for the patient
Known human immunodeficiency virus (HIV) positive
Pregnant or nursing female participants
Unwilling or unable to follow protocol requirements
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