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
Conditions
Brief 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.
Detailed 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.
Interventions
DRUGFludarabine
Given IV
RADIATIONTotal-Body Irradiation
Undergo TBI
Undergo DLI
DRUGCyclophosphamide
Given IV
PROCEDUREPeripheral Blood Stem Cell Transplantation
Undergo PBSC transplant
PROCEDUREAllogeneic Hematopoietic Stem Cell Transplantation
Undergo PBSC transplant
DRUGTacrolimus
Given PO
DRUGMycophenolate mofetil
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
Sidney Kimmel Cancer Center at Thomas Jefferson University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | At 1 year post HSCT | OS will be estimated using Kaplan-Meier curves. The 1-year OS rate and corresponding 95% confidence interval will be estimated from the Kaplan-Meier curve for the OS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse Related Mortality (RRM) | At 1 year post HSCT | Will be reported descriptively. RRM may also be estimated using Kaplan Meier curves and/or cumulative incidence analyses. |
| Non-Relapse Mortality (NRM) | At 1 year post HSCT | Will be reported descriptively. NRM may also be estimated using Kaplan Meier curves and/or cumulative incidence analyses. |
| Incidence and Severity of GVHD | Up to 1 year post HSCT | Will be reported descriptively |
| Engraftment Rates | Up to 1 year post HSCT | Will be reported descriptively |
| Lymphoid Reconstitution | Up to 1 year post HSCT | Lymphoid reconstitution will be evaluated monthly to every other month during the first year post HSCT and will be reported descriptively. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RIC HSCT, GVHD Prophylaxis RIC: Patients receive fludarabine phosphate IV on days -10 to -8 and cyclophosphamide IV on days -3 and -2. Patients also undergo TBI followed by a DLI on day -6.
TRANSPLANT: Patients undergo CD34+ peripheral blood stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus PO beginning day -1 with a taper initiated on day 42 and mycophenolate mofetil IV BID on days -1 to 28 in the absence of GVHD.
Fludarabine: Given IV
Total-Body Irradiation: Undergo TBI
T Cell-Depleted Donor Lymphocyte Infusion: Undergo DLI
Cyclophosphamide: Given IV
Peripheral Blood Stem Cell Transplantation: Undergo PBSC transplant
Allogeneic Hematopoietic Stem Cell Transplantation: Undergo PBSC transplant
Tacrolimus: Given PO
Mycophenolate mofetil: Given IV
Laboratory Biomarker Analysis: Correlative studies | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | RIC HSCT, GVHD Prophylaxis |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 22 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 35 |
| other Total, other adverse events | 33 / 35 |
| serious Total, serious adverse events | 10 / 35 |
Outcome results
Primary
Overall Survival (OS)
OS will be estimated using Kaplan-Meier curves. The 1-year OS rate and corresponding 95% confidence interval will be estimated from the Kaplan-Meier curve for the OS.
Time frame: At 1 year post HSCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RIC HSCT, GVHD Prophylaxis | Overall Survival (OS) | 74 percentage of participants |
Secondary
Engraftment Rates
Will be reported descriptively
Time frame: Up to 1 year post HSCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RIC HSCT, GVHD Prophylaxis | Engraftment Rates | 97 percentage of participants |
Secondary
Incidence and Severity of GVHD
Will be reported descriptively
Time frame: Up to 1 year post HSCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RIC HSCT, GVHD Prophylaxis | Incidence and Severity of GVHD | 27 percentage of participants |
Secondary
Lymphoid Reconstitution
Lymphoid reconstitution will be evaluated monthly to every other month during the first year post HSCT and will be reported descriptively.
Time frame: Up to 1 year post HSCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RIC HSCT, GVHD Prophylaxis | Lymphoid Reconstitution | 10 percentage of participants |
Secondary
Non-Relapse Mortality (NRM)
Will be reported descriptively. NRM may also be estimated using Kaplan Meier curves and/or cumulative incidence analyses.
Time frame: At 1 year post HSCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RIC HSCT, GVHD Prophylaxis | Non-Relapse Mortality (NRM) | 16 percentage of participants |
Secondary
Relapse Related Mortality (RRM)
Will be reported descriptively. RRM may also be estimated using Kaplan Meier curves and/or cumulative incidence analyses.
Time frame: At 1 year post HSCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RIC HSCT, GVHD Prophylaxis | Relapse Related Mortality (RRM) | 13 percentage of participants |