Preventing Stem Cell Transplant Complications With a Blood Separator Machine

Phase 1

Completed

• Conditions: Lymphoma, Non-Hodgkin; AML (Acute Myelogenous Leukemia; Myeloproliferative Disorder; MDS (Myelodysplastic Syndrome); ALL (Acute B-Lymphoblastic Leukemia)
• Interventions: Device: Graft Manipulation (CD34+ Selection)

• Registration Number: NCT01866839
• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Brief Summary

Background:

- Researchers are working to make stem cell transplant procedures safer and more effective. One complication of transplants is graft-versus-host disease (GVHD). This complication happens when certain white blood cells from the donor attack the recipient's own body. Researchers want to test a blood separator machine that may help remove more of the donor's white blood cells before transplant. They will study donors and recipients during stem cell transplant to see how well this process can prevent GVHD and other complications.

Objectives:

- To see if a new blood separator machine can improve outcomes of stem cell transplants.

Eligibility:

* Individuals between 10 and 75 years of age who are having a stem cell transplant for leukemia or other blood-related cancers.

* Donors for the stem cell transplant.

Design:

* Recipients and donors will be screened with a physical exam and medical history.

* Donors will have two blood collection procedures. The first will collect only white blood cells, and return the rest of the blood. After the first collection, participants will have filgrastim injections to help their stem cells enter their blood. Then, they will have a second blood collection for the stem cells.

* Recipients will have radiation and chemotherapy to prepare for the stem cell transplant. They will then have the stem cell transplant with the donor cells that have been treated with the blood separator machine.

* Recipients will be monitored closely after the procedure. They may receive some of their donor's white blood cells if needed to fight serious infections.

* Recipients will have the regular standard of care after their transplant. Blood samples will be taken and any side effects will be monitored and treated.

Detailed Description

Peripheral blood stem cell transplant research carried out by the NHLBI BMT Unit focus on transplant techniques designed to decrease graft versus host disease (GVHD), increase the graft-versus-leukemia (GVL) effect and reduce the risk of post-transplant graft rejection.

Through incremental transplant clinical trials we have shown that by controlling the stem cell (CD34+ cell) and T lymphocyte (CD3+ cell) dose, severe GVHD can be reduced whilst beneficial GVL effects can be preserved. We found that T cell depleted transplants using the Nexell/Baxter Isolex 300i system and subsequently, the Miltenyi CliniMACS\[registered\] CD34+ system to obtain high CD34+ doses depleted of lymphocytes were safe to administer and associated with less severe acute GVHD and promising response rates and overall survival. Our previous trials have helped us to create the transplant environment (significant lymphodepletion and minimal post transplant immunosuppression) that make for an ideal platform for adoptive cellular immunotherapy. Adoptive cell transfer is the passive transfer of immune cells, into a new recipient host with the goal of transferring the immunologic functionality and characteristics into the new host.

This protocol is designed to evaluate the safety and efficacy of the Miltenyi CliniMACS\[registered\] CD 34 selection system in HLA-matched sibling allogeneic peripheral blood stem cell transplant. The manipulation of the graft is the primary research intervention, subject to IDE# 15632, and all other aspects of clinical management on this protocol are standard care. The target CD34+ dose range will be \>3 x 10(6)/kg and the target CD3+ dose range will be 5 x 10(4)/kg to 1 x 10(6)/kg. Once we demonstrate adequacy of this platform for engraftment and absence of significant GVHD in ten consecutive recipients, we will seek IRB permission to proceed with planned adoptive cellular therapies.

The protocol will accrue up to 96 transplant recipients aged 10-80 with a hematological malignancy and their HLA-matched sibling donors, in whom allogeneic stem cell transplantation from an HLA-matched sibling would be routinely indicated. Diagnostic categories will include acute and chronic leukemia, myelodysplastic syndromes, lymphomas, multiple myeloma and myeloproliferative syndromes.

Subjects will receive a myeloablative conditioning regimen of cyclophosphamide (120 mg/kg total), fludarabine (125 mg/m(2) total) and total body irradiation (1200 cGy with lung shielding to 600 cGy), followed by an infusion of a stem cell product selected for CD34+ progenitors using the Miltenyi CliniMACS\[registered\] system. Older subjects will receive a lower dose of irradiation (800 or 600 cGy based on age) to reduce the regimen intensity.

The overall objective is to assess the feasibility of using this system as a platform for cellular immunotherapy initiatives. The primary study endpoint will be overall survival at day +200. Stopping criteria for safety will monitor non-relapse mortality at day +200 and late disease free survival at 2 years. Secondary endpoints will be standard transplant outcome variables such as non-hematologic toxicity, incidence and severity of acute and chronic GVHD and relapse of disease.

Study Timeline

• Study Start: 2013-05-29
• Study First Submitted: 2013-05-29
• Study First Submitted QC: 2013-05-29
• Study First Posted: 2013-06-03
• Primary Completion: 2018-05-23
• Status Verified: 2018-06-28
• Study Completion: 2018-06-28
• Results First Submitted: 2020-05-01
• Results First Submitted QC: 2020-05-01
• Results First Posted: 2020-05-26
• Last Update Submitted: 2020-07-20
• Last Update Posted: 2020-07-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD34+ cell positively selected graft stem cell recipient	Graft Manipulation (CD34+ Selection)	Recipients received a myeloablative conditioning regimen of cyclophosphamide (120 mg/kg total), fludarabine (125 mg/m2 total) and total body irradiation (1200 cGy with lung shielding to 600 cGy), followed by an infusion of a stem cell product selected for CD34+ progenitors using the Miltenyi CliniMACS® system. Older subjects will receive a lower dose of irradiation (800 or 600 cGy based on age) to reduce the regimen intensity.

Primary Outcome Measures

Name	Time	Method
Overall Survival	200 days	Determine the rate of overall survival at 200 day

Secondary Outcome Measures

Name	Time	Method
Incidence of Acute GVHD	100 days	Participants who develop acute GVHD
Severity of Acute GVHD	100 days	Grade IV
Incidence of Chronic GVHD	3 years	Participants who develop chronic GVHD
Severity of Chronic GVHD	3 years	Limited
Disease Free Survival at 2 Years	2 years	Disease Free Survival at 2 years
Median Time to ANC>500/mm3	3 years	Time in days
Disease Progression	3 years	Incidence of relapse / disease progression
Median Time to Platelets>20K/mm3	3 years	Time in days

Trial Locations

Locations (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike; 🇺🇸 Bethesda, Maryland, United States