Bulk Versus Fractionated Stem Cell Infusions in Patients With Hematologic Malignancies Undergoing Stem Cell Transplantation

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to find out if getting a blood stem cell transplant with donor stem cells given over several days is better than getting a blood stem cell transplant with donor stem cells given over 1 day. We want to find out which procedure over will result in improved recovery of blood and immune function after transplant. When donor stem cells are given over various days in mice, the blood and immune system recovery is quicker.

Detailed Description
-----------------
This is a complex study that involves various interventions, Intervention #1: Donor Initial Stem Cell Collection; Intervention #2: Stem Cell Product Initial Processing Orders; Intervention #3 Patient Admission and Transplantation; Intervention #4: Stem cell infusion; Intervention #5: Post infusion follow up; Intervention #6: Off Study Patient and Donor Evaluation. Patients whose donor fails to collect the appropriate number of cells will receive all their cells as a bulk infusion. These patients will continue to receive a transplant on protocol but will be replaced until both arms have reached the target accrual.

Official Title
-----------------
Randomized Phase II Trial of Bulk Versus Fractionated Stem Cell Infusions in Patients With Hematologic Malignancies Undergoing Stem Cell Transplantation

Conditions
-----------------
Leukemia

Intervention / Treatment
-----------------
* Procedure: allogeneic hematopoietic stem cell transplantation
* Device: CliniMACS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who are considered candidates for an allogeneic stem cell transplantation as treatment for any of the following hematologic disorders: Acute Leukemia Myelodysplastic syndrome Other myeloproliferative disorder (i.e. myelofibrosis, chronic myelomonocytic leukemia, or chronic myelogenous leukemia) Non Hodgkins Lymphoma Hodgkins Disease Multiple Myeloma Age includes from birth to < 75 years old. Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status > 70% Patients must have adequate organ function measured by: Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 40% Hepatic: < 5x ULN ALT and < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia. Renal: serum creatinine <1.5 mg/dl or if serum creatinine is outside the normal range, then CrCl > 40 ml/min (measured or calculated/estimated) Pulmonary: asymptomatic or if symptomatic, DLCO > 40% of predicted (corrected for hemoglobin). Exclusion Criteria: Female patients who are pregnant or breast-feeding. Active viral, bacterial or fungal infection Patient seropositive for HIV-I/II; HTLV -I/II Presence of leukemia in the CNS Candidate for a protocol of higher priority. For the purpose of this study, the following protocols will be considered of higher priority: 10-051 Donor Inclusion Criteria: HLA compatible related or unrelated donor, (i.e. a fully matched unmanipulated grafts or 1-2 HLA allele disparate donor for CD34 selected grafts). Meets criteria outlined in the FACT-approved SOP for DONOR EVALUATION AND SELECTION FOR ALLOGENEIC TRANSPLANTATION in the Blood and Marrow Transplant Program Manual, document E-1 see http://mskweb5.mskcc.org/intranet/html/80312.cfm Donor must have adequate peripheral venous catheter access for leukapheresis or must agree to placement of a central catheter. Wt >25kg Donor Exclusion Criteria: Evidence of active infection (including urinary tract infection, or upper respiratory tract Infection) or viral hepatitis exposure (on screening), unless only HBS Ab+ and HBV DNA negative. Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis. Factors which place the donor at increased risk for complications from leukapheresis or GCSF therapy (e.g., autoimmune disease, sickle cell trait, symptomatic coronary artery disease requiring therapy). Pregnancy (positive serum or urine β-HCG) or breastfeeding. Women of childbearing age must avoid becoming pregnant while on the study

Ages Eligible for Study
-----------------
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: bulk SCT<br>Patients receive reduced intensity or myeloablative conditioning regimen, GVHD prophylaxis, and undergo T cell depleted or no T cell depleted allogeneic SCT on day 0. After completion of study treatment, patients are followed up every 6-8 weeks for up to 24 months | Procedure: allogeneic hematopoietic stem cell transplantation<br>* Undergo allogeneic hematopoietic stem cell transplant<br>Device: CliniMACS<br> <br> |
| Experimental: fractionated SCT<br>Patients receive reduced intensity or myeloablative conditioning regimen, GVHD prophylaxis, and undergo T cell depleted or no T cell depleted allogeneic SCT on days 0, 2, 4, and 6. After completion of study treatment, patients are followed up every 6-8 weeks for up to 24 months | Procedure: allogeneic hematopoietic stem cell transplantation<br>* Undergo allogeneic hematopoietic stem cell transplant<br>Device: CliniMACS<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Engraftment of Neutrophils | Determine the effects of fractionated vs. bulk stem cell infusions on neutrophil recovery as defined by number of days with an absolute neutrophil count of less than 500 neutrophils per micro liter and time to an absolute neutrophil count (ANC) of 500. Determing the median time to ANC of >/= 0.5 x 10^9/L | Up to 100 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Assessed for Toxicities | Participants will be assessed for toxicities with the NCI-Common Terminology for Adverse Events (CTCAE), version 4.0. | 2 years | 
| Median Time to Platelet Engraftment | The area under the hematopoietic recovery curve for the factors: ALC, CD4, CD8, and platelet count. The area under the curve will be computed based on recordings at days 30, 60, 100, 180, 365. Determine days to platelet engraftment by platelet count. | Up to 365 days | 
| Overall Survival | Percentage of participants alive at 24 months | 24 months | 
| Hematopoietic Function on Day 30 | Determine the difference of CD4+ lymphocyte recovery between the two arms on day 30 | 30 days | 
| Hematopoietic Function on Day 180 | Determine the difference of CD4+ lymphocyte recovery between the two arms on day 180 | 180 days | 
| Hematopoietic Function on Day 360 | Determine the difference of CD4+ lymphocyte recovery between the two arms on day 360 | 360 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CliniMACS-CD34 Reagent System, Acute Leukemia, Myelodysplastic syndrome, Non Hodgkins Lymphoma, Hodgkins Disease, Multiple Myeloma, 12-016