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
    Jul 1, 2022
  • participants needed
    30
  • sponsor
    Roswell Park Cancer Institute
Updated on 25 November 2020
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 II 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
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 on25 November 2020

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Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 18 yrs and 79 yrs?
Gender: Male or Female
Do you have any of these conditions: Minimal Residual Disease or Chronic Myelomonocytic Leukemia in Remission or Graft-Versus-Host Disease or Waldenstrom Macroglobulinemia or Preleukemia ...?
The patient must have a diagnosis of one of the following (one must be yes)
Acute myeloid leukemia (AML)
Acute lymphoblastic leukemia (ALL)
Chronic myelogenous leukemia (CML) (chronic phase intolerant or unresponsive to tyrosine kinase inhibitors, accelerated phase, history of blast crisis)
Myelodysplastic syndrome (MDS)
Myeloproliferative neoplasm (MPN)
Chronic myelomonocytic leukemia (CMML)
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)
Waldenstrom's macroglobulinemia
Severe aplastic anemia
Histocompatible donor identified
Related donor or unrelated donor matched 5/6 or better (A, B, DRB1)
Patients with benign hematological disorders such as severe aplastic anemia do not have disease requirements. Patients with malignant hematologic disorder must be in CR (MRD is allowed) with the exception of the following
Patients with MDS/MPN only require <5% myeloblast on bone marrow evaluation
Patients with AML or ALL may be in CRi, patients with MM may be in VGPR
Have a Karnofsky performance status score of > 50%
Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% predicted, corrected for hemoglobin and/or alveolar ventilation
Left ventricular ejection fraction > 40%
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 chemotherapy, radiation treatment and/or surgery
Participant or legal representative 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

Bone marrow failure disorders
Paroxysmal nocturnal hemoglobinuria (PNH)
Hereditary bone marrow failure disorders include Diamond-Blackfan anemia, Shwachman- Diamond syndrome, Kostmann syndrome, and congenital amegakaryocytic thrombocytopenia
Other non-malignant hematologic or immunologic disorders that require
transplantation
Quantitative or qualitative congenital platelet disorders (including but not limited to congenital megakaryocytopenia, absent-radii syndrome, Glanzmann?s thrombasthenia)
Quantitative or qualitative congenital neutrophil disorders (including but not limited to chronic granulomatous disease, congenital neutropenia)
Congenital primary immunodeficiencies (including but not limited to severe combined immunodeficiency syndrome, Wiskott-Aldrich syndrome, CD40 ligand deficiency, T-cell deficiencies)
Hemoglobinopathies (including sickle cell disease and thalassemia)
Presence of human leukocyte antigen (HLA) antibodies
Uncontrolled central nervous system (CNS) disease (for hematologic malignancies)
Child-Pugh class B and C liver failure
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
Any condition which in the Investigator?s opinion deems the participant an unsuitable candidate to receive study drug
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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
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