Improving Blood Stem Cell Collection and Transplant Procedures

NCT01517035 | Completed Phase 1

• 2 other identifiers: 12002812-H-0028
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- People who have some kinds of cancer can benefit from donated bone marrow stem cells. These stem cells help produce healthy bone marrow and slow or stop the spread of abnormal cells. However, stem cells transplants do not always work. Also, they may have serious side effects that can cause illness or death. The Bone Marrow Stem Cell Transplant Program is studying methods to make stem cell transplant procedures safer and more effective. Objectives: \- To test a new procedure that may improve the success and decrease the side effects of stem cell transplants. Eligibility:

• Individuals 10 to 75 years of age who have a life-threatening illness that may require a stem cell transplant.
• Healthy siblings who are able to provide stem cells for transplant. Design:
• Participants will be screened with a medical history, physical exam, and blood and urine tests.
• Donor procedures:
• Stem cell donors will start by having apheresis to donate white blood cells.
• Donors will receive filgrastim shots for 5 days to help move stem cells into the blood for collection.
• Donors will have another round of apheresis to donate the stem cells for transplant.
• Recipient procedures:
• Before the transplant, recipients will have radiation twice a day for 3 days and chemotherapy for 7 days.
• After the radiation and chemotherapy, recipients will receive the stem cells provided by the donor.
• After the transplant, recipients will receive the white blood cells provided by the donor.
• Recipients will be monitored closely for 4 months to study the success of the transplant. They will have more followup visits at least yearly thereafter.
• Recipients will have a research apheresis prior to transplant and at 3 months.

Conditions

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

Keywords

Peripheral Blood Stem Cell Transplantation; Stem Cell Transplant; Transplant; Myelodyplastic Syndrome; MDS; Leukemia

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is all cause mortality at day 200, and the proportion of subjects who have survived at day 200 will be used to determine the sample size.

  200 days

Secondary Outcomes (5)

• Cumulative incidence of relapse

  3 years

• Secondary Outcome Measure: Standard transplant outcome variables such as relapse, non-relapse mortality, neutrophil and platelet recovery kinetics, incidence and severity of acute GVHD and chronic GVHD. Technical success rates and the use of DLI...

• Non Relapse Mortality

  3 years

• Days till ANC greater than 500/uL

  variable

• Days till Platelet greater than 20 k/ul

  variable

Study Arms (1)

1

EXPERIMENTAL

Myeloablative conditioning (Flu/Cy/TBI) followed by CD3/19/34 selected stem cell graft.

Procedure: Stem Cell Transplantation

Interventions

Stem Cell Transplantation PROCEDURE

Myeloablative conditioning (Flu/Cy/TBI) followed by CD3/19/34 selected stem cell graft.

1

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:

• RECIPIENT
• Ages 10-75 years inclusive
• Chronic myelogenous leukemia (CML):
• Subjects under the age of 21 in chronic phase
• Subjects ages 10-75 in chronic phase who have failed treatment with imatinib, have intolerance to imatinib, or who did not receive imatinib at therapeutic doses within the first 12 months from diagnosis.
• Subjects ages 10-75 in accelerated phase or blast transformation.
• Acute lymphoblastic leukemia (ALL): any of these categories: ALL in first remission with high-risk features (presenting leukocyte count \>100,000/cu mm, Karyotypes t9; 22, t4, t19, t11, biphenotypic leukemia) All second or subsequent remissions, primary induction failure, partially responding or untreated relapse.
• Acute myelogenous leukemia (AML): AML in first remission - except AML with good risk karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), AML t (8; 21). All AML in second or subsequent remission, primary induction failure and resistant relapse.
• Myelodysplastic syndromes(MDS): any of these categories - refractory anemia with transfusion dependence, refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia, atypical MDS/myeloproliferative syndromes.
• Myeloproliferative disorders including atypical (Ph negative) chronic myeloid and neutrophilic leukemias, progressing myelofibrosis, and polycythemia vera, essential thrombocythemia in transformation to acute leukemia or with progressive transfusion requirements or pancytopenia.
• Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky progressive disease or with thrombocytopenia (less than or equal to 100,000/ micro-l) or anemia (less than or equal to 10g/dl) not due to recent chemotherapy.
• Non-Hodgkin s lymphoma including Mantle cell lymphoma relapsing or refractory to standard of care treatments.
• Multiple myeloma, Waldenstroms macroglobulinemia, unresponsive or relapsed following standard of care treatments.
• HLA identical (6/6) related donor.
• 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 consent from minors: the process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.

You may not qualify if:

• RECIPIENT (any of the following)
• Estimated probability of surviving less than three months
• Major anticipated illness or organ failure incompatible with survival from transplant
• Severe psychiatric illness. 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.
• HIV positive
• 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 (\>grade 3, CTCAE)
• Bilirubin \> 5 times ULN (\>grade 3, CTCAE)
• Creatinine \> 4.5 times ULN (\>grade 3, CTCAE)
• Prior allogeneic stem cell transplantation
• DONOR (any of the following)
• Pregnant or breast-feeding. Lactating donors are permitted provided breastmilk is discarded during the days filgatrim (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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Muller AM, Linderman JA, Florek M, Miklos D, Shizuru JA. Allogeneic T cells impair engraftment and hematopoiesis after stem cell transplantation. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14721-6. doi: 10.1073/pnas.1009220107. Epub 2010 Aug 2.

  PMID: 20679222 BACKGROUND

• Maury S, Lemoine FM, Hicheri Y, Rosenzwajg M, Badoual C, Cherai M, Beaumont JL, Azar N, Dhedin N, Sirvent A, Buzyn A, Rubio MT, Vigouroux S, Montagne O, Bories D, Roudot-Thoraval F, Vernant JP, Cordonnier C, Klatzmann D, Cohen JL. CD4+CD25+ regulatory T cell depletion improves the graft-versus-tumor effect of donor lymphocytes after allogeneic hematopoietic stem cell transplantation. Sci Transl Med. 2010 Jul 21;2(41):41ra52. doi: 10.1126/scitranslmed.3001302.

  PMID: 20650872 BACKGROUND

• Thomson KJ, Morris EC, Milligan D, Parker AN, Hunter AE, Cook G, Bloor AJ, Clark F, Kazmi M, Linch DC, Chakraverty R, Peggs KS, Mackinnon S. T-cell-depleted reduced-intensity transplantation followed by donor leukocyte infusions to promote graft-versus-lymphoma activity results in excellent long-term survival in patients with multiply relapsed follicular lymphoma. J Clin Oncol. 2010 Aug 10;28(23):3695-700. doi: 10.1200/JCO.2009.26.9100. Epub 2010 Jul 6.

  PMID: 20606089 BACKGROUND

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, B-Cell; Leukemia

Interventions

Stem Cell Transplantation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Minocher M Battiwalla, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 24, 2012
• First Posted: January 25, 2012
• Study Start: January 13, 2012
• Primary Completion: March 29, 2017
• Study Completion: March 29, 2017
• Last Updated: July 5, 2018

Record last verified: 2017-03-29

Locations

US (1)