Preventing Stem Cell Transplant Complications With a Blood Separator Machine
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|ClinicalTrials.gov Identifier: NCT01866839|
Recruitment Status : Completed
First Posted : June 3, 2013
Results First Posted : May 26, 2020
Last Update Posted : July 21, 2020
|First Submitted Date ICMJE||May 29, 2013|
|First Posted Date ICMJE||June 3, 2013|
|Results First Submitted Date ICMJE||May 1, 2020|
|Results First Posted Date ICMJE||May 26, 2020|
|Last Update Posted Date||July 21, 2020|
|Study Start Date ICMJE||May 29, 2013|
|Actual Primary Completion Date||May 23, 2018 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Overall Survival [ Time Frame: 200 days ]
Determine the rate of overall survival at 200 day
|Original Primary Outcome Measures ICMJE
||The primary outcome of this protocol is to determine the rate of overall survival at 200 day using the Miltenyi CliniMACS CD34 selection system. [ Time Frame: 200 days ]|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Preventing Stem Cell Transplant Complications With a Blood Separator Machine|
|Official Title ICMJE||Peripheral Blood Stem Cell Allotransplantation For Hematological Malignancies Using Ex Vivo CD34 Selection - a Platform For Adoptive Cellular Therapies|
- 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.
- To see if a new blood separator machine can improve outcomes of stem cell transplants.
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 Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 1
|Study Design ICMJE||Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Intervention ICMJE||Device: Graft Manipulation (CD34+ Selection)|
|Study Arms ICMJE||Experimental: CD34+ cell positively selected graft stem cell recipient
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.
Intervention: Device: Graft Manipulation (CD34+ Selection)
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date ICMJE||June 28, 2018|
|Actual Primary Completion Date||May 23, 2018 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
5.1.1 Ages 10-80 years inclusive
5.1.2 Any one of the following hematologic conditions, confirmed by pathology, meeting a standard indication for allogeneic stem cell transplant:
18.104.22.168 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
22.214.171.124 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
126.96.36.199 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
188.8.131.52 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
184.108.40.206 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
220.127.116.11 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
18.104.22.168 Non-Hodgkin s lymphoma including Mantle cell lymphoma relapsing or refractory to standard of care treatments. OR
22.214.171.124 Multiple myeloma, Waldenstroms macroglobulinemia, unresponsive or relapsed following standard of care treatments. OR
126.96.36.199 Hodgkin's Lymphoma relapsing following an autologous transplant. OR
188.8.131.52 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.
5.1.3 HLA identical (6/6) related donor.
5.1.4 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. Informed oral assent from minors: the process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.
EXCLUSION CRITERIA RECIPIENT (any of the following)
5.2.1 Major anticipated illness or organ failure incompatible with survival from transplant
5.2.2 Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and making informed consent impossible.
5.2.3 Positive pregnancy test for women of childbearing age
5.2.4 DLCO adjusted for Hb and ventilation< 50% predicted
5.2.5 Left ventricular ejection fraction < 40% (evaluated by ECHO) or < 30% (evaluated by MUGA)
5.2.6 AST/SGOT > 10 times ULN
5.2.7 Total bilirubin > 5 times ULN
5.2.8 Estimated GFR < 15 mL/min
5.2.9 Recipients who have active infections with HIV or active hepatitis C (HCV)
INCLUSION CRITERIA DONOR
5.3.1 Related donor, HLA identical (6/6) with recipient
5.3.2 Weight greater than or equal to 18 kg
5.3.3 Age greater than or equal to 2 or less than or equal to 80 years old
5.3.4 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.
EXCLUSION CRITERIA DONOR (any of the following)
5.4.1 Pregnant or breast-feeding. Lactating donors are permitted provided breast milk is discarded during the days filgrastim (G-CSF) is given
5.4.2 Unfit to receive G-CSF and undergo apheresis (abnormal blood counts, history of stroke, uncontrolled hypertension)
5.4.3 Sickling hemoglobinopathy including HbSS, HbSC
5.4.4 Donors who are positive for HIV, active hepatitis B (HBV), hepatitis C (HCV) or human Tcell lymphotropic virus (HTLV-I/II)
5.4.5 Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the donation process unlikely, and making informed consent impossible.
|Ages ICMJE||2 Years to 80 Years (Child, Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01866839|
|Other Study ID Numbers ICMJE||130144
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )|
|Study Sponsor ICMJE||National Heart, Lung, and Blood Institute (NHLBI)|
|Collaborators ICMJE||Children's National Research Institute|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||June 28, 2018|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP