The Role of Cyclosporine in Blood Cell Transplants With T-Cell Add-Back for Blood Cancers

NCT00001873 | Completed Phase 2

• 2 other identifiers: 99004699-H-0046
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

Cancers of the blood, sometimes referred to as hematologic malignancies, are disorders of bone marrow cells that lead to the failure of the normal function of bone marrow and the uncontrolled growth of cancerous cells in the bone marrow. These cancerous cells can spill over into the bloodstream and affect other organs causing widespread symptoms. The disease is life threatening because it blocks the normal function of the marrow, which is to produce red cells (preventing anemia), white cells (preventing infection), and platelets (preventing progression). Bone marrow transplants are a potential form of therapy for patients with hematologic malignancies. However, BMT is a complicated procedure and can be associated with dangerous side effects. In this study researchers are attempting to find ways to reduce the complications of BMT, so that it would be possible to use it more safely and can be offered more patients. In order to do this, researchers are developing new techniques to make BMT safer. It requires making small changes to the standard procedure, which may improve the outcome. The experimental procedures researchers are evaluating are:

1. 1.\<TAB\>T-cell depleted peripheral blood progenitor cell (PBPC) transplantation
2. 2.\<TAB\> Cyclosporine given immediately after the transplant
3. 3.\<TAB\>Add-back of donor lymphocytes

Conditions

Chronic Lymphocytic Leukemia; Graft vs Host Disease; Hematologic Neoplasm; Multiple Myeloma; Myelodysplastic Syndrome

Keywords

Peripheral Blood Stem Cells; Cyclosporine; Cyclosphosphamide; Whole Body Irradiation; Donor Apheresis; Leukemic Relapse; Graft vs. Host Disease; Graft-Versus-Leukemia; Graft-Versus-Myeloma; Chronic Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Acute Myelogenous Leukemia; Myelodysplastic Syndromes; Multiple Myeloma; Chronic Lymphocytic Leukemia; Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (1)

• The proportion of patients with clinically significant acute GHVD (Grade II or higher) following the T depleted PBPC transplant (and before D45 add-back).

  Day 45

Interventions

Isolex 300i plus MoAbs DEVICE

Eligibility Criteria

• Age: 10 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Ages 10-55 years.
• Chronic myelogenous leukemia, any of these categories: chronic phase, accelerated phase or blast transformation.
• Acute lymphoblastic leukemia, any of these categories: Adults (greater than 18 years) in first remission with high-risk features (presenting leukocyte count greater than 100,000/cu mm, karyotypes t9; 22, t4, 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, any of these categories: refractory anemia with transfusion dependence, refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia.
• Myeloproliferative disorders (myelofibrosis, polycythemia vera, essential thrombocythemia) in transformation to acute leukemia.
• Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky progressive disease or with thrombocytopenia (less than or equal to 100,000 / mcl) or anemia (less than or equal to 10g/dl) not due to recent chemotherapy.
• No major organ dysfunction precluding transplantation.
• DLCO greater than or equal to 60% predicted.
• Left ventricular ejection fraction: greater than or equal to 40% predicted.
• ECOG performance status of 0 or 1.
• For adults: Written informed consent given by adults. 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.
• Women of childbearing age with a negative pregnancy test may participate.

You may not qualify if:

• Patient pregnant.
• Age less than 10 and greater than 55 years.
• ECOG performance status of 2 or more.
• Severe psychiatric illness in the patient or donor. Mental deficiency sufficiently severe as to make compliance with the treatment unlikely, and making informed consent impossible.
• Major anticipated illness or organ failure incompatible with survival from transplant.
• DLCO less than 60% predicted.
• Left ventricular ejection fraction: less than 40% predicted.
• Serum creatinine greater than 3mg/dl.
• Serum bilirubin greater than 4 mg/dl.
• Transaminases greater than 3x upper limit of normal.
• HIV positive (donor or recipient).
• History of other malignancies except basal cell or squamous carcinoma of the skin, positive PAP smear and subsequent negative follow up.
• Individuals with diseases listed above as eligible for this protocol, but where debility or age makes the risk of intensive myeloablative therapy unacceptable. These patients will be considered for a non-myeloablative allogeneic transplantation protocol (97-H-0202, 99-H-0050).
• HLA 6/6 identical or 5/6 (one antigen mismatched) family donor.
• Fit to receive G-CSF and give peripheral blood stem cells (normal blood count, normotensive, no history of stroke).

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 (5)

• Schmitz N, Dreger P, Suttorp M, Rohwedder EB, Haferlach T, Loffler H, Hunter A, Russell NH. Primary transplantation of allogeneic peripheral blood progenitor cells mobilized by filgrastim (granulocyte colony-stimulating factor). Blood. 1995 Mar 15;85(6):1666-72.

  PMID: 7534141 BACKGROUND

• Bensinger WI, Weaver CH, Appelbaum FR, Rowley S, Demirer T, Sanders J, Storb R, Buckner CD. Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor. Blood. 1995 Mar 15;85(6):1655-8.

  PMID: 7534140 BACKGROUND

• Veltri S, Smith JW 2nd. Interleukin 1 trials in cancer patients: a review of the toxicity, antitumor and hematopoietic effects. Stem Cells. 1996 Mar;14(2):164-76. doi: 10.1002/stem.140164.

  PMID: 8991536 BACKGROUND

• McIver ZA, Yin F, Hughes T, Battiwalla M, Ito S, Koklanaris E, Haggerty J, Hensel NF, Barrett AJ. Second hematopoietic SCT for leukemia relapsing after myeloablative T cell-depleted transplants does not prolong survival. Bone Marrow Transplant. 2013 Sep;48(9):1192-7. doi: 10.1038/bmt.2013.39. Epub 2013 Mar 25.

  PMID: 23524640 DERIVED

• McIver Z, Melenhorst JJ, Wu C, Grim A, Ito S, Cho I, Hensel N, Battiwalla M, Barrett AJ. Donor lymphocyte count and thymic activity predict lymphocyte recovery and outcomes after matched-sibling hematopoietic stem cell transplant. Haematologica. 2013 Mar;98(3):346-52. doi: 10.3324/haematol.2012.072991. Epub 2012 Oct 12.

  PMID: 23065508 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Graft vs Host Disease; Hematologic Neoplasms; Multiple Myeloma; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Bone Marrow Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Lymphoma

Study Officials

• A. John Barrett, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: February 22, 1999
• Primary Completion: December 28, 2007
• Study Completion: June 13, 2017
• Last Updated: September 26, 2018

Record last verified: 2017-06-13

Locations

US (1)