Combined Haploidentical-Cord Blood Transplantation for Adults and Children

Study Overview
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Brief Summary
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The primary objective is to assess the rate of engraftment with combined haploidentical-cord blood transplantation. The secondary objective is to evaluate the incidence and severity of acute and chronic graft-versus-host disease (GVHD).

Official Title
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Combined Haploidentical-Cord Blood Transplantation for Adults and Children

Conditions
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Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, Lymphoma

Intervention / Treatment
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* Drug: Fludarabine-Melphalan & Rabbit antithymocyte globulin (r-ATG)
* Procedure: Stem Cell Transplant
* Procedure: Stem Cells Collections
* Drug: Fludarabine, Thiotepa, Antithymocyte globulin (ATG), and Total Body Irradiation (TBI)
* Drug: Fludarabine, Busulfan, and ATG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients will be eligible for this study if they have any one of the diseases that are known to be cured after allogeneic stem cell transplantation. 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(PFT's) 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

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Good Risks patients<br>For patients transplanted in remission. | Drug: Fludarabine-Melphalan & Rabbit antithymocyte globulin (r-ATG)<br>* Fludarabine is given through the vein daily for 5 days. Melphalan is given through the vein daily for 2 days. ATG is given every day in the vein for four days.<br>Procedure: Stem Cell Transplant<br>* Infusion of haploidentical donor, umbilical cord blood<br>Procedure: Stem Cells Collections<br>* Haploidentical cells will be T-cell depleted using the Miltenyi Clinimax device.<br>|
| Experimental: High Risk Patients eligible for radiation<br> | Procedure: Stem Cell Transplant<br>* Infusion of haploidentical donor, umbilical cord blood<br>Procedure: Stem Cells Collections<br>* Haploidentical cells will be T-cell depleted using the Miltenyi Clinimax device.<br>Drug: Fludarabine, Thiotepa, Antithymocyte globulin (ATG), and Total Body Irradiation (TBI)<br>* Fludarabine is given through the vein daily for 5 days. Thiotepa is given through the vein daily for 2 days. ATG is given through the vein every other day for 4 days. TBI is given twice a day for 3 days.<br>|
| Experimental: High Risk Patients not eligible for radiation<br> | Procedure: Stem Cell Transplant<br>* Infusion of haploidentical donor, umbilical cord blood<br>Procedure: Stem Cells Collections<br>* Haploidentical cells will be T-cell depleted using the Miltenyi Clinimax device.<br>Drug: Fludarabine, Busulfan, and ATG<br>* Fludarabine is given through the vein daily for 5 days. Busulfan is given through the vein daily for 4 days. ATG is given through the vein every other day for 4 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Neutrophil Engraftment | Cumulative incidence of graft failure (neutrophil) by day 28 was reported. Patients who did not have neutrophil engraftment before death was considered as a competing risk. Failure to engraft was defined as lack of evidence of hematopoietic recovery (ANC <500/mm3 and platelet count < 20,000/mm3) by day +35, confirmed by a biopsy revealing a marrow cellularity < 5%. Graft failure was also defined as initial myeloid engraftment by day +35, documented to be of donor origin, followed by a drop in the ANC to < 500/mm3 for more than three days, independent of any myelosuppressive drugs, severe GVHD, CMV, or other infection. | Transplant (Day 0) through Day +28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Incidence of Acute (Grade II-IV) and Chronic Graft-vs-host Disease(GVHD) | Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+). Chronic GVHD is assessed by NIH consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11:945-56., for grading criteria. (See Citation: Filipovich AH et al) The incidence of patients with acute GVHD (Grade II-IV) was determined at 180 days. The incidence of Chronic GVHD by 2 years was reported | Up to 2 years | 
| Overall Survival- Percentage of Participants Who Survived at 2 Years and 5 Years | We reported overall survival at 2 years and 5 years after transplant | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Appropriate candidate for transplantation, An HLA-identical related or unrelated donor cannot be identified within an appropriate time frame.