GM-CSF With Post-Transplant Cyclophosphamide

Study Overview
=================
Brief Summary
-----------------
Given the increased number of HLA-mismatched haploidentical transplantation with post-transplant cyclophosphamide performed each year and the high risk of infectious complications associated with this type of transplant, the investigators suggest that GM-CSF administration post-infusion of T-replete haploidentical stem cells and post-transplant cyclophosphamide can yield similar count recovery rates to G-CSF with a potential of lowering risk of infectious complications.

Official Title
-----------------
Phase II Trial Evaluating the Efficacy and Safety of Sargramostim Post-Infusion of T-Replete HLA Mismatched Peripheral Blood Haploidentical Hematopoietic Stem Cells and With Post Transplant Cyclophosphamide

Conditions
-----------------
Transplant-Related Hematologic Malignancy

Intervention / Treatment
-----------------
* Drug: Sargramostim
* Other: Control Arm


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Availability of 5/10 to 8/10 matched related donor KPS >/= 70% CML, AML, MDS, ALL, CLL, HD, NHL, MPS/CMML, MM, any other hematologic condition deemed an eligible indication for allogeneic transplant by the treating center Exclusion Criteria: Poor cardiac, pulmonary, liver, and renal function HIV-positive Patients who have a debilitating medical or psychiatric illness that would preclude them from giving informed consent History of severe or serious allergic reaction to human GM-CSF or yeast-derived products

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 78 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GM-CSF post-transplant<br>Sargramostim (GM-CSF) will start on Day +5 and continue until ANC >1000 x3 days or >1500 x1 day. GM-CSF will be administered not less than 24 hours after the last dose of cyclophosphamide and will be given at a dose of 250mcg/m2/day as an infusion over 2 hours. | Drug: Sargramostim<br>* 250mcg/m2/day IV starting Day +5<br>* Other names: GM-CSF;Other: Control Arm<br>* Standard G-CSF given to those who decline to receive GM-CSF<br>* Other names: G-CSF;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients who achieved neutrophil engraftment at 20 days after the initiation of treatment. | The aim of the study is to establish equivalent effectiveness of Sargramostim to a matched control cohort of G-CSF treated patients in time to achieve neutrophil (ANC >500 x3 days) post infusion of HLA-mismatched peripheral blood haploidentical stem cells with post-transplant cyclophosphamide. Patients will be followed for 3 months following the initiation of treatment to see engraftment numbers at 20 days after initial treatment. | 3 months after initial treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| How many patients are still alive measured by overall survival at 12 months following the initiation of treatment. | To estimate overall survival | 12 months following initiation of treatment | 
| How many patients have not relapsed measured by relapse rates at 12 months following the initiation of treatment. | To estimate relapse rates | 12 months following initiation of treatment | 
| How many patients develop graft-versus-host-disease (GVHD) measured by the incidence of GVHD at 12 months following initiation of treatment | To estimate incidence of GVHD | 12 months following initiation of treatment | 
| How many patients have not relapsed measured by progression-free survival at 12 months following the initiation of treatment | To estimate non-relapse mortality | 12 months following initiation of treatment | 
| How many patients died due to infections measured by the incidence and type of infections at 12 months following initiation of treatment | To estimate infection-related mortality | 12 months following initiation of treatment | 
| How many patients died due to a treatment-related adverse events grade 2 or greater as assessed by CTCAE v.4.0 | To estimate event-free survival | 12 months following initiation of treatment | 
| Number of patients to achieve full donor chimerisms at Days 30, 50, 100, and 6 months post-transplant as measured by donor chimerism data | To estimate graft failure | 12 months following initiation of treatment | 
| Number of patients that acquired an infection in the first 100-days post-transplant as measured by the incidence of infections | To estimate the rate of infections | 12 months following initiation of treatment | 
| Number of patients achieving platelet engraftment as measured by platelets reaching 20,000 without transfusion for 7 days | To assess time to platelet engraftment | 12 months following initiation of treatment |