Preventing Stem Cell Transplant Complications With a Blood Separator Machine

NCT01866839 | Completed Phase 1 Results FDA Device

• 2 other identifiers: 13014413-H-0144
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

MDS (Myelodysplastic Syndrome); Myeloproliferative Disorder; Lymphoma, Non-Hodgkin; ALL (Acute B-Lymphoblastic Leukemia); AML (Acute Myelogenous Leukemia

Keywords

Acute Lymphoblastic Leukemia (ALL); Acute Myelogenous Leukemia (AML); Chronic Lymphocytic Leukemia (CLL); Chronic Myelogenous Leukemia (CML); Myelodysplastic Syndrome (MDS)

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Determine the rate of overall survival at 200 day

  200 days

Secondary Outcomes (12)

• Disease Free Survival at 2 Years

  2 years

• Disease Progression

  3 years

• Incidence of Acute GVHD

  100 days

• Incidence of Chronic GVHD

  3 years

• Median Time to ANC>500/mm3

  3 years

Study Arms (1)

CD34+ cell positively selected graft stem cell recipient

EXPERIMENTAL

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.

Device: Graft Manipulation (CD34+ Selection)

Interventions

Graft Manipulation (CD34+ Selection) DEVICE

CD34+ cell positively selected graft stem cell recipient

Eligibility Criteria

• Age: 2 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 10-80 years inclusive
• Any one of the following hematologic conditions, confirmed by pathology, meeting a standard indication for allogeneic stem cell transplant:
• Chronic myelogenous leukemia (CML): Subjects under the age of 21 in chronic phase OR Subjects ages 10-80 in chronic phase who have failed or are intolerant to treatment with second generation tyrosine inhibitors OR Subjects ages 10-80 in accelerated phase or blast transformation. OR
• Acute lymphoblastic leukemia (ALL): any of these categories: Adult ALL including standard risk; Pediatric ALL in first remission with high-risk features (presenting leukocyte count \>100,000/cu mm, karyotypes t(9; 22), t4, t19, t11, biphenotypic leukemia). All second or subsequent remissions, primary induction failure, partially responding or untreated relapse. OR
• Acute myelogenous leukemia (AML): AML in first remission - except AML with good risk karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), c-kit unmutated AML t (8; 21). All AML in second or subsequent remission, primary induction failure and resistant relapse. OR
• Myelodysplastic syndromes(MDS): any of these categories - refractory anemia with transfusion dependence, refractory anemia with ANC\<500/microL, refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia, atypical MDS/myeloproliferative syndromes. OR
• Myeloproliferative disorders including atypical (Ph-negative) chronic myeloid and neutrophilic leukemias, progressing myelofibrosis, and polycythemia vera, essential thrombocythemia either in transformation to acute leukemia or with progressive transfusion requirements or pancytopenia. OR
• Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky progressive disease or with thrombocytopenia (less than or equal to 100,000 / microl) or anemia (less than or equal to 10g/dl) not due to recent chemotherapy. OR
• Non-Hodgkin s lymphoma including Mantle cell lymphoma relapsing or refractory to standard of care treatments. OR
• Multiple myeloma, Waldenstroms macroglobulinemia, unresponsive or relapsed following standard of care treatments. OR
• Hodgkin's Lymphoma relapsing following an autologous transplant. OR
• Other rare hematologic malignancies for which hematopoietic stem cell transplantation has been performed and offers a durable remission or as the only option for potential for cure.
• Chemotherapy-resistant multisystem Langerhans cell histiocytosis (MSLCH) especially involving organs like the bone marrow, liver, spleen, and lungs
• Aggressive systemic mastocytosis, and mast cell leukemia (MCL) in first CR (CR1)
• Hypereosinophilic syndrome who have failed imatinib therapy or FIP1L1-PDGFRa-negative patients who develop end-organ dysfunction

You may not qualify if:

• Major anticipated illness or organ failure incompatible with survival from transplant
• Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and making informed consent impossible.
• Positive pregnancy test for women of childbearing age
• DLCO adjusted for Hb and ventilation\< 50% predicted
• Left ventricular ejection fraction \< 40% (evaluated by ECHO) or \< 30% (evaluated by MUGA)
• AST/SGOT \> 10 times ULN
• Total bilirubin \> 5 times ULN
• Estimated GFR \< 15 mL/min
• Recipients who have active infections with HIV or active hepatitis C (HCV)
• Related donor, HLA identical (6/6) with recipient
• Weight greater than or equal to 18 kg
• Age greater than or equal to 2 or less than or equal to 80 years old
• For adults: ability to comprehend the investigational nature of the study and provide informed consent. For minors: written informed consent from one parent or guardian and informed assent: The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.
• Pregnant or breast-feeding. Lactating donors are permitted provided breast milk is discarded during the days filgrastim (G-CSF) is given
• Unfit to receive G-CSF and undergo apheresis (abnormal blood counts, history of stroke, uncontrolled hypertension)

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead
• Children's National Research Institute: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Armitage JO. Bone marrow transplantation. N Engl J Med. 1994 Mar 24;330(12):827-38. doi: 10.1056/NEJM199403243301206. No abstract available.

  PMID: 8114836 BACKGROUND

• Barrett AJ. Graft-versus-host disease: basic considerations. Recent Results Cancer Res. 1993;132:185-95. doi: 10.1007/978-3-642-84899-5_19. No abstract available.

  PMID: 8265860 BACKGROUND

• Appelbaum FR. Haematopoietic cell transplantation as immunotherapy. Nature. 2001 May 17;411(6835):385-9. doi: 10.1038/35077251.

  PMID: 11357147 BACKGROUND

MeSH Terms

Conditions

Anemia, Refractory, with Excess of Blasts; Myeloproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Anemia, Refractory; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Leukemia, Lymphoid; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

1 participant signed consent but did not start study.

Results Point of Contact

• Title: Aue, Georg
• Organization: National Heart Lung and Blood Institute

aueg@nhlbi.nih.gov

+1 301 451 7141

Study Officials

• Sawa Ito, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2013
• First Posted: June 3, 2013
• Study Start: May 29, 2013
• Primary Completion: May 23, 2018
• Study Completion: June 28, 2018
• Last Updated: July 21, 2020
• Results First Posted: May 26, 2020

Record last verified: 2018-06-28

Locations

US (1)