Hematological Disease
Conditions
Brief summary
The primary objective of this study is to assess the rate of engraftment with combined haploidentical-cord blood transplantation in patients with pre-existing donor specific antibodies and in those with active disease.
Detailed description
Primary Objective \- To assess the rate of engraftment with combined haploidentical-cord blood transplantation in patients with pre-existing donor specific anti-HLA antibodies and in those with active disease Secondary Objectives * To determine the long term fate of the haplo transplant and the cord blood transplant in this setting. * To describe the incidence and severity of acute and chronic GVHD.
Interventions
DRUGMelphalan
Melphalan is given daily for 2 days, overlapping with the completion of fludarabine.
DRUGFludarabine
Fludarabine is given through the vein daily for 5 days.
ATG is given every other day for 4 days.
DRUGBusulfan
Busulfan is given daily for 4 days.
DRUGTotal Body Irradiation (TBI)
TBI is given twice on the last day.
Sponsors
University of Chicago
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Relapsed or refractory acute leukemia (myeloid or lymphoid) * Acute leukemia in first remission at high-risk for recurrence * Chronic myelogenous leukemia in accelerated phase or blast-crisis * Chronic myelogenous leukemia in chronic phase * Recurrent or refractory malignant lymphoma or Hodgkin lymphoma * Chronic lymphocytic leukemia, relapsed or with poor prognostic features * Multiple myeloma * Myelodysplastic syndrome * Chronic myeloproliferative disease * Hemoglobinopathies * Aplastic anemia
Exclusion criteria
* Zubrod performance status \> 2 * Life expectancy is severely limited by concomitant illness * Patients with severely decreased LVEF or impaired pulmonary function tests * Estimated Creatinine Clearance \<50 ml/min * Serum bilirubin\> 2.0 mg/dl or SGPT \>3 x upper limit of normal * Evidence of chronic active hepatitis or cirrhosis * HIV-positive * Patient is pregnant * Patient or guardian not able to sign informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cord Blood Engraftment by Day 100 | 100 days | Percent of subjects with cord blood engraftment on or before day 100. Detectable cord blood engraftment should be present by day 100 in at least 50% of patients. As of 44 days post-transplant, only haploidentical donor chimerism achieved in the one patient enrolled in the Fludarabine, melphalan, and ATG arm. There were no cord cells detected for this patient. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival at Day 100 | 100 days | Percent of subjects who are alive 100 days after the stem cell infusion |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fludarabine, Melphalan, and ATG Arm I contains fludarabine, melphalan, and antithymocyte globulin (ATG)
Melphalan: Melphalan is given daily for 2 days, overlapping with the completion of fludarabine.
Fludarabine: Fludarabine is given through the vein daily for 5 days.
Antithymocyte Globulin (ATG): ATG is given every other day for 4 days. | 1 |
| Fludarabine, Busulfan, ATG, and TBI Arm II contains fludarabine, busulfan, antithymocyte globulin (ATG), and total body irradiation (TBI).
Fludarabine: Fludarabine is given through the vein daily for 5 days.
Antithymocyte Globulin (ATG): ATG is given every other day for 4 days.
Busulfan: Busulfan is given daily for 4 days.
Total Body Irradiation (TBI): TBI is given twice on the last day. | 0 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
Baseline characteristics
| Characteristic | Fludarabine, Melphalan, and ATG | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 participants | 0 participants |
| Age, Categorical >=65 years | 0 participants | 0 participants |
| Age, Categorical Between 18 and 65 years | 1 participants | 1 participants |
| Gender Female | 0 participants | 0 participants |
| Gender Male | 1 participants | 1 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 1 / 1 | 0 / 0 |
Outcome results
Primary
Cord Blood Engraftment by Day 100
Percent of subjects with cord blood engraftment on or before day 100. Detectable cord blood engraftment should be present by day 100 in at least 50% of patients. As of 44 days post-transplant, only haploidentical donor chimerism achieved in the one patient enrolled in the Fludarabine, melphalan, and ATG arm. There were no cord cells detected for this patient.
Time frame: 100 days
Population: The only enrolled patient failed to complete the study due to death.
Secondary
Survival at Day 100
Percent of subjects who are alive 100 days after the stem cell infusion
Time frame: 100 days
Population: The only enrolled patient failed to complete the study due to death.