Chronic Myelogenous Leukemia, Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Myelofibrosis, CMML, Multiple Myeloma
Conditions
Keywords
CML, AML, MDS, ALL, CLL/CPL, HD, NHL, MPS, CMML, MM
Brief summary
This trial will evaluate the safety and efficacy of a reduced intensity allogeneic HSCT from partially HLA-mismatched first-degree relatives utilizing PBSC as the stem cell source. The primary objective of the study is to estimate the incidence of graft rejection and acute GVHD. A secondary objective will be to estimate the incidence of the relapse, NRM, OS, chronic GVHD and EFS.
Detailed description
Patients will receive a haploidentical transpalnt using a fludarabine melphalan prepartive regimen. Patients will get cyclophosphamide on days 3 & 4 post-transplant.
Interventions
DRUGFludarabine
fludarabine (30mg/m2) given every day starting on Day -6 through Day -2;
DRUGMelphalan
DRUGCyclophosphamide
cyclophosphamide (50mg/kg) given every day starting on Day 3 through Day 4.
Sponsors
Blood and Marrow Transplant Group of Georgia
Northside Hospital, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* No available matched related or unrelated donor, OR a matched related or unrelated donor will not be available in time frame necessary to perform potentially curative transplant * Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor (donor must have negative HLA cross-match in host vs. graft direction) * Karnofsky status ≥70% * One of the following high-risk malignancies: 1. Chronic Myelogenous Leukemia: Chronic myelogenous leukemia in chronic phase, resistant or intolerant to available tyrosine kinase inhibitors; Chronic myelogenous leukemia in accelerated phase; Chronic myelogenous leukemia with blast crisis that has entered into a second chronic phase following induction chemotherapy 2. Acute Myelogenous Leukemia in first or greater remission 3. Myelodysplastic Syndrome at least one of the following: treatment-related; monosmy 7, complex cytogenetics or other high risk karyotype; IPSS score of 1.0 or greater; neutropenia or cytopenia requiring transfusion not responding to therapy; peripheral or BM blast count of \<10%; CMML 4. Acute lymphocytic leukemia/lymphoblastic lymphoma: 2nd or subsequent complete remission; first complete remission; marrow blasts \<5%, but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH 5. Chronic Lymphocytic Leukemia/Prolymphocytic Leukemia: previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs 6. Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse): previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation 7. Myeloproliferative diseases (myelofibrosis, CMML) 8. Multiple Myeloma with relapse after a prior autologous transplant or eligible for allogeneic HSCT based on other risk factors
Exclusion criteria
* not be excluded on basis of sex, racial, or ethnic backgrounds * poor cardiac function: left ventricular ejection fraction \<40% * poor pulmonary function: FEV1 and FVC \<50% predicted * poor liver function: bilirubin \>2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy) * poor renal function: Creatinine \>2.0mg/dl or creatinine clearance (calculated creatinine clearance is permitted) \< 40 mL/min based on Traditional Cockcroft-Gault formula: 140 - age (yrs) x Smaller of Actual Weight vs. Ideal Body Weight (kg) / 72 x Serum creatinine (mg/dl) * HIV-positive * prior allogeneic transplant * women of childbearing potential who currently are pregnant or who are not practicing adequate contraception * any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Graft Rejection | 100 days | Measurement of donor cells vs. recipient cells |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 2 years | Number of participants still alive 2 years after transplant |
| Relapse Incidence | 2 years | Number of patients with disease reoccurrence at 1 and 2 years post-transplant |
| GVHD Incidence | 100 days | The number of participants that developed graft-versus-host-disease before or at 100 days after transplant |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Reduced-Intensity Mismatched Transplant Fludarabine, Melphalan & Post-transplant cyclophosphamide
Fludarabine: fludarabine (30mg/m2) given every day starting on Day -6 through Day -2;
Melphalan
Cyclophosphamide: cyclophosphamide (50mg/kg) given every day starting on Day 3 through Day 4.
peripheral blood stem cell transplant | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Reduced-Intensity Mismatched Transplant | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 3 Participants | — |
| Age, Categorical Between 18 and 65 years | 22 Participants | — |
| Age, Continuous | 57 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 25 participants | — |
| Sex: Female, Male Female | 13 Participants | — |
| Sex: Female, Male Male | 12 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 25 |
| other Total, other adverse events | 25 / 25 |
| serious Total, serious adverse events | 23 / 25 |
Outcome results
Primary
Graft Rejection
Measurement of donor cells vs. recipient cells
Time frame: 100 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced-Intensity Mismatched Transplant | Graft Rejection | 3 Participants |
Secondary
GVHD Incidence
The number of participants that developed graft-versus-host-disease before or at 100 days after transplant
Time frame: 100 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reduced-Intensity Mismatched Transplant | GVHD Incidence | Grades II to IV acute GVHD | 20 percentage of patients |
| Reduced-Intensity Mismatched Transplant | GVHD Incidence | Grades III to IV acute GVHD | 8 percentage of patients |
| Reduced-Intensity Mismatched Transplant | GVHD Incidence | Moderate chronic GVHD | 16 percentage of patients |
| Reduced-Intensity Mismatched Transplant | GVHD Incidence | Severe chronic GVHD | 12 percentage of patients |
Secondary
Overall Survival
Number of participants still alive 2 years after transplant
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reduced-Intensity Mismatched Transplant | Overall Survival | 1 yr post-transplant | 68 percentage of patients |
| Reduced-Intensity Mismatched Transplant | Overall Survival | 2 yr post-transplant | 56 percentage of patients |
Secondary
Relapse Incidence
Number of patients with disease reoccurrence at 1 and 2 years post-transplant
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reduced-Intensity Mismatched Transplant | Relapse Incidence | 1 yr post-transplant | 24 percentage of patients |
| Reduced-Intensity Mismatched Transplant | Relapse Incidence | 2 yr post-transplant | 36 percentage of patients |