Hematological Malignancies, Hodgkin's Disease, Leukemia, Lymphoma, Multiple Myeloma
Conditions
Keywords
Myeloablative Hematopoietic Stem Cell Transplant, Cyclophosphamide tolerization, 2 Step Approach, Hematological malignancies, leukemia, lymphoma, multiple myeloma, Hodgkin's Disease
Brief summary
This research study uses a drug called cyclophosphamide to decrease the incidence of GVHD in matched sibling hematopoietic stem cell transplant. In doing so, the goal of the study is to increase overall survival.
Detailed description
This research protocol has been developed for patients undergoing matched-sibling hematopoietic stem cell transplant (HSCT). The patients who are treated according to this 2 step allogeneic HSCT protocol will receive cyclophosphamide to induce in-vivo tolerization of both autologous and allogeneic lymphocytes, followed by an allogeneic CD34-selected HSCT. The primary research questions relate to immune reconstitution, incidence of GVHD, and relapse in patients who receive lymphocyte treatment of this type in allogeneic HSCT and how it impacts overall survival.
Interventions
DEVICEMatched Sibling Allogeneic Transplantation
Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization
Sponsors
Sidney Kimmel Comprehensive 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
1. Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. Patients will be considered high-risk if they have any of the following: 1. Age \> 50 years 2. ECOG Performance status of \<2 3. Acute leukemia: requiring more than one chemotherapy regimen to obtain 1st CR; second or greater CR, 1st relapse; any ph+ ALL 4. CML 2nd chronic phase, accelerated phase, or blastic phase 5. MDS with IPS of Intermediate 2 or greater 6. Any myeloproliferative disorder 7. Hodgkin lymphoma: relapsed, refractory, or primary induction failure 8. Non-Hodgkin lymphoma: relapsed, refractory, primary treatment failure, or not eligible for an autologous HSCT 9. Other conditions not listed will be assessed as high-risk by the PI 2. Patients must have a related donor who is either HLA-identical or a one antigen mismatch at the HLA- A; B; C; and DR loci. 3. Patients must adequate organ function: 1. LVEF of \>45% 2. DLCO (adjusted for hemoglobin) \>45% of predicted 3. Adequate liver function as defined by a serum bilirubin \<1.8, AST or ALT \< 2.5X upper limit of normal 4. Creatinine clearance of \> 60 ml/min 4. Patients must be willing to use contraception if they have childbearing potential 5. Able to give informed consent
Exclusion criteria
1. ECOG performance status of 3 or 4. 2. HIV positive 3. Active involvement of the central nervous system with malignancy 4. Psychiatric disorder that would preclude patients from signing an informed consent 5. Pregnancy 6. Patients with life expectancy of \< 6 months for reasons other than their underlying hematologic/oncologic disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Overall Survival | 1 Year after transplant | The primary objective of this prospective, phase II trial was to obtain an OS rate of \>60% at 1 year in patients undergoing a 2 step HSCT from an HLA compatible family donor. The \>60% threshold was selected as a composite efficacy measure as patients with any hematologic diagnosis, stage of disease, or age as old as 65 years were eligible for this treatment protocol. |
Secondary
| Measure | Time frame |
|---|---|
| Graft Versus Host Disease (GVHD) | 1 Year after transplant |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNeal Flomenberg, MD
Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Allogeneic Transplantation Matched Sibling Allogeneic Transplantation
Matched Sibling Allogeneic Transplantation: Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization | 46 |
| Total | 46 |
Baseline characteristics
| Characteristic | Allogeneic Transplantation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 35 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 4 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 | 37 Participants |
| Region of Enrollment United States | 46 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 46 |
| other Total, other adverse events | 32 / 46 |
| serious Total, serious adverse events | 0 / 46 |
Outcome results
Primary
Number of Patients With Overall Survival
The primary objective of this prospective, phase II trial was to obtain an OS rate of \>60% at 1 year in patients undergoing a 2 step HSCT from an HLA compatible family donor. The \>60% threshold was selected as a composite efficacy measure as patients with any hematologic diagnosis, stage of disease, or age as old as 65 years were eligible for this treatment protocol.
Time frame: 1 Year after transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Allogeneic Transplantation | Number of Patients With Overall Survival | 41 Participants |
Secondary
Graft Versus Host Disease (GVHD)
Time frame: 1 Year after transplant
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Allogeneic Transplantation | Graft Versus Host Disease (GVHD) | Acute GVHD | 6 Participants |
| Allogeneic Transplantation | Graft Versus Host Disease (GVHD) | Chronic GVHD | 4 Participants |
| Allogeneic Transplantation | Graft Versus Host Disease (GVHD) | No GVHD | 36 Participants |