Blood Cancer, Leukemia, Graft Versus Host Disease, Malignancy, CLL, NHL, Hodgkin's Disease, MDS
Conditions
Brief summary
The purpose of the study is to evaluate the feasibility and safety of transplanting CD34+ selected hematopoietic cells from a haploidentical related donor following a nonmyeloablative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG).
Detailed description
An alternative to conventional allogeneic bone marrow transplantation is by using a non-myeloablative conditioning regimen. This regime would consist of both; total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG). Used in combination to achieve engraftment of haploidentical CD34+ selected peripheral blood stem cells in older patients or patients with underlying medical conditions that preclude standard allogeneic treatment. The expected results of this transplant regime will be expected to result in hematopoietic and immunologic reconstitution, decreased deaths related to the treatment regimen and decreased gravft-vs-host disease (GVHD).
Interventions
PROCEDUREnon-myeloablative hematopoietic cell transplantation
TLI and ATG infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil.
DRUGAnti-Thymocyte Globulin
1.5 mg/kg QD x 5, IV. Dosage will be based on body weight. Purified, sterile IgG fraction of immune serum of rabbits immumixied with human thymus lymphocyte. This drug acts to modify the number and function of lymphocytes.
DRUGCyclosporine
6.25 mg/kg BID, PO.Mechanism of action is inhibition of T-cell activation by binding to a cytoplasmic protein (cyclophillin).
DRUGMycophenolate Mofetil
15 mg/kg Q 8 hours, PO. Inhibtis the enzme inosine monophsophate dehydrogenase (MPDII) noncompetitively which blocks the de nobo synthesis of guanosine required for DNA synthesis and has an effect on T and B cells.
DRUGG-CSF
16 mg/kg, SQ Growth factor used to make bone marrow produce more blood cells
DRUGSolumedrol
1.0 mg/kg IV 2 hours prior to ATG Used to treat severe inflamation
DRUGAcetaminophen
650 mg PO, 30 minutes prior to infusion Pain reliever
DRUGDiphenydramine
50 mg IV, 30 minutes prior to infusion Used to relieve allergy symptoms
DRUGHydrocortisone
100 mg IV, 1 hour prior to infusion Used to relieve itching, redness and swelling of the skin
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 50 years with hematologic malignancies treatable by a mixed chimera allogeneic HCT. * For patients ≤ 50 years of age with hematologic malignacies treatable with mixed chimera HCT who because of pre-exisiting medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional transplants. * Indolent advanced stage NHL, CLL, HD - Must have received and failed front-line therapy. * Multiple myeloma (Stage II or III) - Must have received prior chemotherapy. Consolidation after prior autografting is permitted. * AML/ALL - Must be in complete hematologic remission and have received cytotoxic chemotherapy at some stage before transplant. Patients with molecular or cytogenetic relapse will be accepted providing a donor is available. Patients with persistent or refractory disease will be considered on a case by case basis and transplants must be approved by the principal investigator. * CML - Patients will be accepted in chronic or accelerated phase. Patients who have received prior autografts after high dose therapy or have undergone intensive chemotherapy for either peripheral blood stem cell mobilization or treatment of advanced CML may be enrolled provided they are in CR, chronic phase or accelerated phase. * MDS - All patients with MDS will be eligible for this protocol, however, those patients with \>10% blasts will require chemotherapy to reduce the blast % to \< 10%. * SAA - Patients with severe aplastic anemia who have failed front line therapy. * A fully HLA-identical sibling donor is not available. * A matched unrelated donor has not been identified. * A haploidentical related donor is available who is in good health and does not have contraindications to donation.
Exclusion criteria
* Patients with rapidly progressive intermediate or high grade NHL * Uncontrolled CNS involvement with disease * Fertile men * Women unwilling to use contraceptive techniques during and for 12 months following treatment * Females who are pregnant * Cardiac function: ejection fraction \< 30% or cardiac failure requiring therapy * Pulmonary: DLCO \< 40% predicted and/or receiving supplementary continuous oxygen * Liver function abnormalities: elevation of bilirubin to \> 4 mg/dl and/or transaminases \> 3x the upper limit of normal. If hyperbilirubinemai is due to a known cause that will not increase the risks of transplant, than this upper limit may be exceeded. * Renal: creatinine clearance \< 50 cc/min (24 hour urine collection) * Karnofsky performance score \< 60% * Patients with poorly controlled hypertension. * Documented fungal disease that persists despite treatment * HIV positive patients. * Hepatitis B and C positive patients will be evaluated on a case by case basis * Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or principal investigator would place the patient at unacceptable risk from this regimen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Engraftment of Haploidentical CD34+ Selected Blood Stem Cells in Older Patients or Those With Medical Co-morbidities Following Total Lymphoid Irradiation and Antithymocyte Globulin Transplant Conditioning | 100 days | number achieving donor cell engraftment (\>95%) by day 90 after transplant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Graft-versus-Host Disease (GVHD) Grade 2-4 Risk From Time of Transplant Until Day 90 Post-transplant | 90 days | GVHD grading system goes from 0-4 where grade 4 is the most severe. Grade 0 and 1 do not require systemic treatment, Grade 2-4 require treatment. This trial evaluated the risk of developing acute GVHD grades 2-4 within 90 days of transplant. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Transplating of CD34+ Selected Hematopietic Cells | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Transplating of CD34+ Selected Hematopietic Cells |
|---|---|
| Age, Continuous | 52 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 14 / 16 |
Outcome results
Primary
Engraftment of Haploidentical CD34+ Selected Blood Stem Cells in Older Patients or Those With Medical Co-morbidities Following Total Lymphoid Irradiation and Antithymocyte Globulin Transplant Conditioning
number achieving donor cell engraftment (\>95%) by day 90 after transplant.
Time frame: 100 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Transplantation of CD34+ Cells | Engraftment of Haploidentical CD34+ Selected Blood Stem Cells in Older Patients or Those With Medical Co-morbidities Following Total Lymphoid Irradiation and Antithymocyte Globulin Transplant Conditioning | 4 Participants |
Secondary
Acute Graft-versus-Host Disease (GVHD) Grade 2-4 Risk From Time of Transplant Until Day 90 Post-transplant
GVHD grading system goes from 0-4 where grade 4 is the most severe. Grade 0 and 1 do not require systemic treatment, Grade 2-4 require treatment. This trial evaluated the risk of developing acute GVHD grades 2-4 within 90 days of transplant.
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Transplantation of CD34+ Cells | Acute Graft-versus-Host Disease (GVHD) Grade 2-4 Risk From Time of Transplant Until Day 90 Post-transplant | 1 Participants |