Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Biphenotypic Acute Leukemia, Burkitt Lymphoma, Chronic Myelogenous Leukemia, Hodgkin Lymphoma, Lymphoplasmacytic Lymphoma, Mantle Cell Lymphoma, Myelodysplastic Syndromes, Myeloproliferative Neoplasm, Prolymphocytic Leukemia, Relapsed Chronic Lymphocytic Leukemia, Relapsed Follicular Lymphoma, Relapsed Large Cell Lymphoma, Relapsed Marginal B-cell Lymphoma, Relapsed Small Lymphocytic Lymphoma, Relapsed T-Cell Lymphoma, Undifferentiated Leukemia
Conditions
Brief summary
This is a single arm, phase II trial of HLA-haploidentical related hematopoietic cells transplant (Haplo-HCT) using reduced intensity conditioning (fludarabine and melphalan and total body irradiation). Peripheral blood is the donor graft source. This study is designed to estimate disease-free survival (DFS) at 18 months post-transplant.
Interventions
DRUGFludarabine
Fludarabine 30mg/m\^2/day will be administered over 30-60 minutes intravenous infusion on Days -6 through -2 for a total dose of 150 mg/m\^2
DRUGMelphalan
Melphalan 70 mg/m\^2 over 45 minutes will be administered Day -6. Melphalan dose will be calculated based on Actual Body Weight.
RADIATIONTotal Body Irradiation
Total Body Irradiation (TBI) will be delivered at a dose of 200 centigray units (cGy)
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
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
* Age ≥ 55 years or HCT Co-Morbidity score (HCT-CI) \>/=3 * Lack of a suitable 8/8 HLA-matched sibling donor * Adequate performance status is defined as Karnofsky score ≥ 70% * Patients and selected donor must be HLA typed at high resolution using DNA based typing at the following HLA-loci: HLA-A, -B, -C and DRB1. Donors must be HLA-haploidentical relatives including, but not limited to, children, siblings, or parents, defined as having a shared HLA haplotype between donor and patient at HLA-A, -B, -C, and -DRB1. * Acute Myeloid Leukemia (AML): Must be in remission with morphology (\<5% blasts) * Acute Lymphoblastic Leukemia (ALL)/lymphoma second or greater complete remission (CR) first CR unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities, first CR high-risk ALL * Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR * Myelodysplastic syndrome: any subtype including refractory anemia (RA) if severe pancytopenia or complex cytogenetics. Blasts must be less than 5%. If 5% of more requires chemotherapy for cytoreduction to \</=5% prior to transplantation. * Chronic Myelogenous leukemia in accelerated phase: patient must have failed at least two different Tyrosine Kinase Inhibitor (TKI)s, been intolerant to all TKIs, or have T315l mutation * Myeloproliferative neoplasms/myelofibrosis: Blasts must be less than 5%. If 5% or more requires chemotherapy for cytoreduction to \</=5% prior to transplantation * Relapsed large-cell lymphoma, mantle-cell lymphoma or Hodgkin lymphoma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant * Burkitt's lymphoma in second CR or subsequent CR * Relapsed T-cell lymphoma that is chemotherapy sensitive in CR/Partial Response (PR) that has failed or ineligible for an autologous transplant * Natural killer cell malignancies * Relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma with any of the following: * Progressed within 12 months of achieving a partial or complete remission Patients who had remissions lasting up * Patients who had remission lasting \> 12 months are eligible after at least two prior therapies * Patients with primary, refractory disease. Bulky disease and an estimated tumor doubling time of less than one month require debulking therapy prior to transplant. * Lymphoplasmacytic lymphoma is eligible after initial therapy if chemotherapy sensitive * Adequate organ function as defined per protocol * Sexually active females of child bearing potential and males with partners of child bearing potential must agree to use adequate birth control during study treatment
Exclusion criteria
* Pregnant or breastfeeding * Untreated active infection * Active HIV infection * Prior allogenic transplant at any time prior or less than 6 months since prior autologous transplant (if applicable) * Active central nervous system malignancy * Favorable risk AML defined as per protocol * Active central nervous system malignancy * Favorable risk AML defined as having one of the following: * t(8,21) without cKIT mutation or evidence of immunophenotypic, cytogenetic or molecular minimal residual disease (MRD) * inv(16) or t(16;16) without cKIT mutation or evidence of MRD * Normal karyotype with mutated NPM1 but FLT3-ITD wild type without evidence of MRD * Normal karyatype with double mutated CEBPA without evidence of MRD
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival | Up to 18 months post-transplant | Disease Free Survival (DFS) is defined as the time from the date of Peripheral Blood Stem Cell Transplant (PBSCT) to first documentation of relapse or death due to any cause, whichever comes first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Graft vs Host Disease (GVHD) Free Survival | At 180 days post-transplant | GVHD-free survival is defined as the time from the date of PBSCT to date of events which include grade III-IV acute GVHD and systemic therapy-requiring chronic GVHD. |
| Percentage of Participants Overall Survival (OS) | Up to 18 months | OS is defined as the time from the date of PBSCT to the date of death due to any cause. |
| Percentage of Participants With Treatment Related Mortality (TRM) at 6 Months | at 6 months post-transplant | TRM is defined as death not directly due to disease |
| Percentage of Participants With Treatment Related Mortality (TRM) at 18 Months | at 18 months post-transplant | TRM is defined as death not directly due to disease |
| Percentage of Participants With Relapse Free Survival (RFS) | Up to 18 months post-transplant | RFS is defined as the time from the date of PBSCT to relapse or death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Conditioning Regimen + Transplant All participants will receive a conditioning regimen of Fludarabine, Melphalan and Total Body Irradiation prior to transplantation of HLA-Haploidentical Related Hematopoietic Cells (Haplo-HCT)
Fludarabine: Fludarabine 30mg/m\^2/day will be administered over 30-60 minutes intravenous infusion on Days -6 through -2 for a total dose of 150 mg/m\^2
Melphalan: Melphalan 70 mg/m\^2 over 45 minutes will be administered Day -6. Melphalan dose will be calculated based on Actual Body Weight.
Total Body Irradiation: Total Body Irradiation (TBI) will be delivered at a dose of 200 centigray units (cGy) | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | Conditioning Regimen + Transplant |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 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 | 2 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 34 |
| other Total, other adverse events | 16 / 34 |
| serious Total, serious adverse events | 21 / 34 |
Outcome results
Primary
Disease Free Survival
Disease Free Survival (DFS) is defined as the time from the date of Peripheral Blood Stem Cell Transplant (PBSCT) to first documentation of relapse or death due to any cause, whichever comes first.
Time frame: Up to 18 months post-transplant
Population: Evaluable Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conditioning Regimen + Transplant | Disease Free Survival | 70.6 percentage of participants |
p-value: 0.002Log Rank
Secondary
Percentage of Participants Overall Survival (OS)
OS is defined as the time from the date of PBSCT to the date of death due to any cause.
Time frame: Up to 18 months
Population: Evaluable Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conditioning Regimen + Transplant | Percentage of Participants Overall Survival (OS) | 73.3 percentage of participants |
Secondary
Percentage of Participants With Graft vs Host Disease (GVHD) Free Survival
GVHD-free survival is defined as the time from the date of PBSCT to date of events which include grade III-IV acute GVHD and systemic therapy-requiring chronic GVHD.
Time frame: At 180 days post-transplant
Population: Evaluable Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conditioning Regimen + Transplant | Percentage of Participants With Graft vs Host Disease (GVHD) Free Survival | 61.8 percentage of participants |
Secondary
Percentage of Participants With Relapse Free Survival (RFS)
RFS is defined as the time from the date of PBSCT to relapse or death.
Time frame: Up to 18 months post-transplant
Population: Evaluable Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conditioning Regimen + Transplant | Percentage of Participants With Relapse Free Survival (RFS) | 70.6 percentage of participants |
Secondary
Percentage of Participants With Treatment Related Mortality (TRM) at 18 Months
TRM is defined as death not directly due to disease
Time frame: at 18 months post-transplant
Population: Evaluable Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conditioning Regimen + Transplant | Percentage of Participants With Treatment Related Mortality (TRM) at 18 Months | 17.6 percentage of participants |
Secondary
Percentage of Participants With Treatment Related Mortality (TRM) at 6 Months
TRM is defined as death not directly due to disease
Time frame: at 6 months post-transplant
Population: Evaluable Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conditioning Regimen + Transplant | Percentage of Participants With Treatment Related Mortality (TRM) at 6 Months | 17.6 percentage of participants |