CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant

Diane George

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Acute Lymphoblastic Leukemia (ALL); Myelodysplastic Syndrome (MDS); Chronic Myeloid Leukemia (CML); Acute Myelogenous Leukemia (AML); Juvenile Myelomonocytic Leukemia (JMML); Lymphoma (Hodgkin's and Non-Hodgkin's)

Treatments: Device: CliniMACS CD34+ Reagent System; Drug: Methylprednisolone; Drug: Busulfan; Drug: Alemtuzumab; Drug: Melphalan; Drug: Thiotepa; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Tacrolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT02061800

AAAK8060

Details and patient eligibility

About

The purpose of this study is to learn more about the effects of (classification determinant) CD34+ stem cell selection on graft versus host disease (GVHD) in children, adolescents, and young adults. CD34+ stem cells are the cells that make all the types of blood cells in the body. GVHD is a condition that results from a reaction of transplanted donor T-lymphocytes (a kind of white blood cell) against the recipient's body and organs. Study subjects will be offered treatment involving the use of the CliniMACS® Reagent System (Miltenyi Biotec), a CD34+ selection device to remove T-cells from a peripheral blood stem cell transplant in order to decrease the risk of acute and chronic GVHD.

This study involves subjects who are diagnosed with a malignant disease, that has either failed standard therapy or is unlikely to be cured with standard non-transplant therapy, who will receive a peripheral blood stem cell transplant. A malignant disease includes the following: Chronic Myeloid Leukemia (CML) in chronic phase, accelerated phase or blast crisis; Acute Myelogenous Leukemia (AML); Myelodysplastic Syndrome (MDS); Juvenile Myelomonocytic Leukemia (JMML); Acute Lymphoblastic Leukemia (ALL); or Lymphoma (Hodgkin's and Non-Hodgkin's).

Full description

Graft versus host disease (GVHD) is one of the serious complications following allogeneic stem cell transplantation. The incidence and severity of GVHD increase with the degree of HLA incompatibility between the host and donor. The most reliable way to prevent acute and chronic GVHD is to remove T cells from the graft. However, the incidence of graft failure increases with the efficiency of T cell depletion and low T cell numbers are predictive of graft failure. Immunomagnetic selection of HLA-mismatched CD34+ progenitor cells has demonstrated high levels of T cell depletion and successful engraftment in adult and pediatric patients with the malignant and nonmalignant disease.

Enrollment: 14 patients

Sex: All

Ages: Under 22 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: General Eligibility (All Patients)

• Must be < 22 years of age
• Diagnosed with a malignant disease
• Must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects), and must sign an informed consent
• For unrelated donor: A human leukocyte antigen (HLA) 8/10, 9/10 or 10/10 matched unrelated adult donor (MUD) will be required for study entry
• For related donor: A 5/10, 6/10, 7/10, 8/10, 9/10 or 10/10 matched (or partially matched) family donor will be required for study entry
• Adequate renal function
• Adequate liver function
• Adequate cardiac function
• Adequate pulmonary function

Exclusion Criteria:

• Patients with documented uncontrolled infection at the time of study entry are not eligible
• Females who are pregnant or breast feeding at the time of study entry are not eligible

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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14 participants in 3 patient groups

Full intensity with TBI

Active Comparator group

Description:

Patients will start their pre-conditioning regimen on 8 days before scheduled transplant. Fractionated total body irradiation (TBI) will be administered twice daily on the 6th, 7th, and 8th before transplant. Patients will receive Thiotepa on the 4th and 5th day before transplant, Cyclophosphamide on the 2nd and 3rd day before transplant, and Alemtuzumab on the 1st-5th day(s) before transplant. Then the stem cell infusion will be performed (allogeneic family member or ≥ 8/10 HLA matched adult unrelated donor peripheral blood stem cell transplantation with CD34 Selection using CliniMACS CD34+ Reagent System). GVHD prophylaxis will consist of tacrolimus only. Tacrolimus administration will begin on the day after transplant, and methylprednisolone will start on day -5.

Treatment:

Drug: Tacrolimus

Drug: Cyclophosphamide

Drug: Thiotepa

Drug: Alemtuzumab

Drug: Methylprednisolone

Device: CliniMACS CD34+ Reagent System

Full intensity without TBI

Experimental group

Description:

Patients will start their pre-conditioning regimen 9 days before their scheduled transplant. Patients will receive busulfan twice daily on the 5th-8th day before transplant, and Melphalan on the 2nd-4th days before transplant and Alemtuzumab on the 1st-5th day before transplant. Subjects will then undergo with their stem cell infusion (allogeneic family member or ≥ 8/10 HLA matched adult unrelated donor peripheral blood stem cell transplantation with CD34 Selection using CliniMACS CD34+ Reagent System) and GVHD prophylaxis will consist of tacrolimus only. Tacrolimus administration will begin on the day after their transplant, and methylprednisolone will start on day -5.

Treatment:

Drug: Tacrolimus

Drug: Melphalan

Drug: Busulfan

Drug: Alemtuzumab

Drug: Methylprednisolone

Device: CliniMACS CD34+ Reagent System

Reduced intensity

Experimental group

Description:

Patients will begin tacrolimus 8 days pre-transplant, and then will receive alemtuzumab on the 3rd-7th day pre-transplant; busulfan twice daily on the 5th-8th day pre-transplant; and fludarabine on the 2nd-7th day pre-transplant. Methylprednisolone will start on day -7.The stem cell infusion will be performed (with CD34 Selection using CliniMACS CD34+ Reagent System). GVHD prophylaxis will consist of tacrolimus or sirolimus. For patients with a history of hepatic toxicity and/or high-risk for veno-occlusive disease or other liver toxicity post stem cell transplant, melphalan at 70 mg/m2 will be substituted for Busulfan, followed by fludarabine on the 2nd-7th day before transplant and alemtuzumab on the 3rd-7th day before transplant.

Treatment:

Drug: Tacrolimus

Drug: Fludarabine

Drug: Busulfan

Drug: Alemtuzumab

Drug: Methylprednisolone

Device: CliniMACS CD34+ Reagent System