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

• Register: ClinicalTrials.gov
• Last refreshed on: 21 August 2023
• Main ID: NCT02566304
• Date of registration: 30/09/2015
• Prospective Registration: Yes
• Primary sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Public title: Reduced Intensity Chemotherapy and Radiation Therapy Before Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies
• Scientific title: A Two Step Approach to Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies
• Date of first enrolment: November 13, 2015
• Target sample size: 35
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02566304
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Usama Gergis, MD
• Affiliation: Thomas Jefferson University

Key inclusion & exclusion criteria

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

- Hodgkin or Indolent non-Hodgkin's lymphoma

- Myeloma with < 5% plasma cells in the marrow

- Myeloproliferative disorders (excludes chronic myelomonocytic leukemia [CMML])

- Aplastic anemia

- 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
2, 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

- Patients must have had front line therapy for their disease

- 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

- 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

- Patients must be willing to use contraception if they have childbearing potential

Exclusion Criteria:

- 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

- Active involvement of the central nervous system with malignancy

- Inability to obtain informed consent from patient or surrogate

- Pregnancy

- 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

- Patients with evidence of another malignancy, exclusive of a skin cancer that requires
only local treatment, should not be enrolled on this protocol



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Chronic Myelomonocytic Leukemia

Refractory Anemia

Acute Myeloid Leukemia

Indolent Non-Hodgkin Lymphoma

Malignant Neoplasm

Myeloproliferative Neoplasm

Refractory Cytopenia With Multilineage Dysplasia

Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

Acute Myeloid Leukemia in Remission

Refractory Anemia With Ring Sideroblasts

Plasma Cell Myeloma

Refractory Anemia With Excess Blasts

Aplastic Anemia

Hodgkin Lymphoma

Myelodysplastic Syndrome

Intervention(s)

Radiation: Total-Body Irradiation

Biological: T Cell-Depleted Donor Lymphocyte Infusion

Other: Laboratory Biomarker Analysis

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

Drug: Cyclophosphamide

Drug: Mycophenolate mofetil

Drug: Tacrolimus

Procedure: Peripheral Blood Stem Cell Transplantation

Drug: Fludarabine

Primary Outcome(s)

Overall Survival (OS) [Time Frame: At 1 year post HSCT]

Secondary Outcome(s)

Incidence and severity of GVHD [Time Frame: Up to 1 year post HSCT]

Non-Relapse Mortality (NRM) [Time Frame: At 1 year post HSCT]

Relapse Related Mortality (RRM) [Time Frame: At 1 year post HSCT]

Engraftment rates [Time Frame: Up to 1 year post HSCT]

Lymphoid reconstitution [Time Frame: Up to 1 year post HSCT]

Secondary ID(s)

NCI-2015-01506

15D.323

2015-054

Source(s) of Monetary Support

Please refer to primary and secondary sponsors