Brief Title
Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies
Official Title
A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Hematologic Malignancies
Brief Summary
This phase II trial studies reduced-intensity conditioning before donor stem cell transplant
in treating patients with high-risk hematologic malignancies. Giving low-doses of
chemotherapy and total-body irradiation before a donor stem cell transplant helps 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). Giving an infusion of the
donor's T cells (donor lymphocyte infusion) before the transplant may help increase this
effect.
Detailed Description
PRIMARY OBJECTIVES:
I. To compare the rate of disease-free survival (DFS) at 1 year post hematopoietic stem cell
transplant (HSCT) in patients undergoing HSCT treated on this successor Thomas Jefferson
University (TJU) 2 Step reduced intensity conditioning (RIC) haploidentical regimen and
compare it with that of the initial 2 Step RIC regimen.
SECONDARY OBJECTIVES:
I. To assess the 100 day regimen-related mortality (RRM) in patients undergoing HSCT on this
treatment protocol.
II. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients
undergoing treatment on this regimen.
III. To evaluate engraftment rates and lymphoid reconstitution in patients treated on this
trial.
IV. To assess overall survival at 1 and 3 years past HSCT in patients treated on this trial.
OUTLINE:
REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on
days -15 to -12, busulfan IV on days -14 to -13, donor lymphocyte infusion (DLI) on day -6,
and cyclophosphamide IV on days -3 and -2. Patients also undergo total-body irradiation (TBI)
on day -10.
TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day
0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV on days -1 to 42 followed by taper and
mycophenolate mofetil IV twice daily (BID) on days -1 to 28.
After completion of study treatment, patients are followed up periodically.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Disease-free survival (DFS)
Secondary Outcome
Overall survival
Condition
Acute Myeloid Leukemia With FLT3/ITD Mutation
Intervention
Fludarabine phosphate
Study Arms / Comparison Groups
Treatment (RIC and allogeneic PBSCT)
Description: REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV on days -15 to -12, busulfan IV on days -14 to -13, DLI on day -6, and cyclophosphamide IV on days -3 and -2. Patients also undergo TBI on day -10. TRANSPLANT: Patients undergo allogeneic PBSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV on days -1 to 42 followed by taper and mycophenolate mofetil IV BID on days -1 to 28
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
62
Start Date
December 24, 2012
Completion Date
December 5, 2022
Primary Completion Date
April 15, 2022
Eligibility Criteria
Inclusion Criteria:
- By definition, patients with hematological malignancies or dyscrasias that require
HSCT as part of cure-directed therapy are by definition high-risk and can be treated
on this protocol; examples of high risk patients include but are not limited to:
- Acute myeloid leukemia with high risk features as defined by:
- Age greater than or equal to 60
- Secondary acute myeloid leukemia (AML) (prior therapy or hematologic
malignancy)
- Normal cytogenetics but fms-related tyrosine kinase 3 (FLT3)/internal tandem
duplication (ITD) positive
- Any relapse or primary refractory disease
- Greater than 3 cytogenetic abnormalities or any one of the following
cytogenetic abnormalities: -5/del(5q), -7/del(7q), Abn(9q), (11q), (3q),
(21q), (17p), t(6;9), t(6;11), t(11;19), +8, del(12p), inv(3), t(10;11),
-17, 11q 23
- Any single autosomal monosomy
- Acute lymphoid leukemia in 1st or 2nd morphological remission; ALL with any
morphological evidence of disease will not be eligible
- Myelodysplasia (MDS) other than refractory anemia (RA), refractory anemia with
rare sideroblasts (RARS), or isolated 5q- syndrome subtypes
- Hodgkin's or Non-Hodgkin's lymphoma in 2nd or greater remission or with
persistent disease
- Myeloma with evidence of persistent disease after front-line therapy
- Chronic myeloid leukemia (CML) resistant to signal transducer inhibitor (STI)
therapy
- Myelofibrosis and chronic myelomonocytic leukemia (CMML)
- Essential thrombocytopenia or polycythemia vera with current or past evidence of
evolution to acute leukemia
- Patients with chronic lymphocytic leukemia (CLL), follicular non-Hodgkin lymphoma
(NHL), or other lymphoid malignancies who have highly adverse cytogenetics (such
as p53 deletion), are chemo-insensitive, are not responsive to highly effective
novel treatments such as chimeric antigen receptor T-lymphocytes (CART) or
Ibrutinib, or who have transformed disease
- Any hematological malignancy not cited above which is thought to be high-risk
with increased chance of post HSCT relapse
- Any patient who has an aggressive disease that would normally be treated on a
myeloablative study, but is prevented from doing so by factors in their past
medical history; examples are patients with previous treatment with radiation
therapy precluding TBI, or a past history of myeloablative therapy, precluding a
2nd myeloablative regimen
- Patients with aplastic anemia may be treated on this protocol, with outcomes
reported descriptively
- Patients must have a related donor who is at least a 2-4/8 antigen mismatch at the
human leukocyte antigen (HLA)-A; B; C; DR loci; patients with only a 1 out of 8
mismatch in the GVH direction will be classified in the matched related category
- Left ventricular end diastolic function (LVEF) of >= 50%
- Diffusion lung capacity of oxygen (DLCO) >= 50% of predicted corrected for hemoglobin
- Serum bilirubin =< 1.8
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x upper
limit of normal
- Creatinine clearance of >= 60 mL/min
- Patients < age 60 years must have a Karnofsky performance status (KPS) of >= 80% and a
hematopoietic cell transplant comorbidity index (HCT-CI) score of 5 or less
- Patients aged 60 to 65 years must have a KPS of >= 80% and an HCT-CI score of 4 or
less
- Patients aged 66 to 69 years must have a KPS of 90% and an HCT-CI score of 3 or less
- Patients aged 70 years or more must have a KPS of 90% and an HCT-CI score of 2 or less
* (Patients with greater than the allowable HCT-CI points for age can be enrolled for
trial with approval of the principal investigator [PI] and at least 1 co-investigator
[Co-I] not on the primary care team of the patient) this is an adjustment to account
for healthy patients who meet the spirit of this protocol but have histories that
result in higher than guideline HCT-CI 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
- Patients must be willing to use contraception if they have childbearing potential
- Patient or patient's guardian is able to give informed consent
Exclusion Criteria:
- Human immunodeficiency virus (HIV) positive
- Active involvement of the central nervous system with malignancy; this can be
documented as a normal neurological exam and/or a negative cerebrospinal fluid (CSF)
analysis
- Pregnancy
- Patients with life expectancy of =< 6 months for reasons other than their underlying
hematologic/oncologic disorder
- Patients who have received alemtuzumab or ATG within 8 weeks of the transplant
admission
- Patients with evidence of another malignancy, exclusive of a skin cancer that requires
only local treatment, should not be enrolled on this protocol
Gender
All
Ages
N/A - N/A
Accepts Healthy Volunteers
No
Contacts
Dolores Grosso, RN, CRNP, DNP, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01760655
Organization ID
12D.501
Secondary IDs
2012-67
Responsible Party
Sponsor
Study Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Dolores Grosso, RN, CRNP, DNP, Principal Investigator, Thomas Jefferson University
Verification Date
January 2023