Reduced Intensity Chemotherapy and Radiation Therapy Before Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

  • STATUS
    Recruiting
  • End date
    Jul 29, 2023
  • participants needed
    35
  • sponsor
    Sidney Kimmel Cancer Center at Thomas Jefferson University
Updated on 29 June 2022
cancer
remission
stem cell transplantation
graft versus host disease
myeloid leukemia
total body irradiation
fludarabine
hematologic malignancy
tacrolimus
anemia
mycophenolate mofetil
cyclophosphamide
hla-a
lymphoma
multiple myeloma
hodgkin's disease
myeloproliferative disorder
graft-versus-tumor
chronic myelomonocytic leukemia
carbon monoxide
cell transplantation
leukemia
bone marrow procedure
cytopenia
serum bilirubin
induction therapy
serum bilirubin level
neoadjuvant therapy
blast cells
blood transfusion
chemotherapy regimen
primary cancer
myelomonocytic leukemia
solid tumor
donor lymphocyte infusion
aplastic anemia
refractory cytopenia with multilineage dysplasia
raeb i
myelodysplastic syndrome with excess blasts-2
refractory anemia with excess blasts-2
refractory anemia with ringed sideroblasts
refractory anemia with excess blasts-1

Summary

This clinical trial studies the use of reduced intensity chemotherapy and radiation therapy before donor stem cell transplant in treating patients with hematologic malignancies. Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine phosphate, before a donor stem cell transplant may help stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Reducing the intensity of the chemotherapy and radiation may also reduce the side effects of the donor stem cell transplant.

Description

PRIMARY OBJECTIVES:

I. To demonstrate efficacy of this approach over the historical 2 step reduced intensity conditioning (RIC) approaches in the "vulnerable" population defined as: patients with hematopoietic cell transplant (HCT)-co-morbidity index (CI)/age scores >= 2, but no more than a score of 5 as based on the Sorror et al. data.

SECONDARY OBJECTIVES:

I. To compare the non-relapse mortality (NRM) and relapse related mortality (RRM) rates at 1 year for patients treated on this study to the that of patients undergoing haploidentical RIC hematopoietic stem cell transplantation (HSCT) as reported in the literature and as observed in the 2 step RIC trials.

II. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treated on the Thomas Jefferson University (TJU) RIC 2 step approach.

III. To evaluate engraftment rates and lymphoid reconstitution in patients treated on the TJU RIC 2 step approach.

OUTLINE

RIC: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -10 to -8 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients also undergo total body irradiation (TBI) followed by a donor lymphocyte infusion (DLI) on day -6.

TRANSPLANT: Patients undergo cluster of differentiation (CD)34+ peripheral blood stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus orally (PO) beginning day -1 with a taper initiated on day 42 and mycophenolate mofetil IV twice daily (BID) on days -1 to 28 in the absence of GVHD.

After completion of study treatment, patients are followed up for 1 year.

Details
Condition Acute Myeloid Leukemia, Acute Myeloid Leukemia in Remission, Aplastic Anemia, Chronic Myelomonocytic Leukemia, Hodgkin Lymphoma, Indolent Non-Hodgkin Lymphoma, Malignant Neoplasm, Myelodysplastic Syndrome, Myeloproliferative Neoplasm, Plasma Cell Myeloma, Refractory Anemia, Refractory Anemia With Excess Blasts, Refractory Anemia With Ring Sideroblasts, Refractory Cytopenia With Multilineage Dysplasia, Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts
Treatment cyclophosphamide, mycophenolate mofetil, laboratory biomarker analysis, allogeneic hematopoietic stem cell transplantation, peripheral blood stem cell transplantation, Fludarabine, Tacrolimus, Total-Body Irradiation, T Cell-Depleted Donor Lymphocyte Infusion
Clinical Study IdentifierNCT02566304
SponsorSidney Kimmel Cancer Center at Thomas Jefferson University
Last Modified on29 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients treated on this study will have
Acute myeloid leukemia in morphologic complete remission (CR) not requiring treatment for their disease for 4 weeks
A history of acute myeloid leukemia (AML) with < 10% residual blasts (use highest count on staging studies) after induction therapy and persisting with < 10% blasts for at least 8 weeks without reinduction and at the time of HSCT
Refractory anemia (RA) or refractory anemia with ring sideroblasts (RARS) or isolated 5q-
Refractory anemia with excess blasts (RAEB)-1, refractory cytopenia with multilineage dysplasia (RCMD)+/-ringed sideroblasts (RS), or myelodysplastic syndrome (MDS) not otherwise specified (NOS) with stable disease for at least 3 months
RAEB-2 must demonstrate chemo-responsiveness; chemo-responsiveness is defined as a persistent blast percentage decrease by at least 5 percentage points to therapy and there must be =< 10% blasts (use highest count on staging studies) after treatment and at the time of transplant
Myeloma with < 5% plasma cells in the marrow
Myeloproliferative disorders (excludes chronic myelomonocytic leukemia [CMML])
A hematological or oncological disease (not listed) in which allogeneic HSCT is thought to be beneficial, and the disease is chemoresponsive
Patients without clear manifestation of their disease status in terms of stage and/or responsiveness should be discussed with the principal investigator (PI) and enrollment analysis should be documented in the study records
Patients must have a related donor who is human leukocyte antigen (HLA) mismatched at
Patients must have had front line therapy for their disease
3, or 4 antigens at the HLA-A; B; C; DR loci in the graft-versus-host
disease (GVHD) direction; (patients with related donors who are HLA identical
or are a 1-antigen mismatch may be treated on this therapeutic approach, but
will have their outcomes will not be part of the statistical aims of the
study); the HLA matched related category includes patients with a syngeneic
donor
LVEF (left ventricular end diastolic function) of >= 45%
DLCO (diffusing capacity of the lung for carbon monoxide) >= 45% of predicted corrected for hemoglobin, FEV-1 (forced expiratory volume at 1 second) >= 50% of predicted
Patients must be willing to use contraception if they have childbearing potential
Serum bilirubin =< 1.8
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 X upper limit of normal
Creatinine clearance of >= 60 mL/min
HCT-CI/age score =< 5 points (patients with greater than 5 points will be allowed for trial with approval of the PI and the co-PI or his designee; this is an adjustment to account for healthy patients who meet the spirit of this protocol but have histories that result in higher than HCT-CI 5 points; an example is a patient with a solid tumor malignancy in their remote history [adds 3 points to HCT-CI total] where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities)
Karnofsky performance status (KPS) >= 90% patients older than 70 years, KPS >= 80% patients younger than 70 years

Exclusion Criteria

Active involvement of the central nervous system with malignancy
Inability to obtain informed consent from patient or surrogate
Pregnancy
Performance status < 90% in patients 70 years old or greater, < 80% in patients less than age 70 years
HCT-CI/age score > 5 points (patients with greater than 5 points will be allowed for trial with approval of the principal investigator and the co-principal investigator or his designee; this is an adjustment to account for healthy patients who meet the spirit of this protocol but have histories that result in higher than HCT-CI 5 points; an example is a patient with a solid tumor malignancy in their remote history [adds 3 points to HCT-CI total] where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities)
A diagnosis of chronic myelomonocytic leukemia (CMML), unless in morphologic CR
Human immunodeficiency virus (HIV) positive
Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol
Patients with life expectancy of =< 6 months for reasons other than their underlying hematologic/oncologic disorder
Patients who have received alemtuzumab or antithymocyte globulin within 8 weeks of the transplant admission; the absence of these therapies in the medical record will serve as documentation that they were not given
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