Bone Marrow Transplant Studies for Safe and Effective Treatment of Leukemia

NCT00001623 | Completed

• 2 other identifiers: 97009997-H-0099
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Bone marrow transplants (BMT) are one of the accepted therapies used to treat leukemia. However, BMT have risks of complications. One potentially life-threatening complication is known as graft-versus-host disease (GVHD). The GVHD is a reaction caused by an incompatibility between donor cells and recipient cells. Antigens found on the recipient s cells are recognized by the donor s transplanted white blood cell lymphocytes. These lymphocytes begin attacking the recipient s cells and tissues and may lead to death. One of the most effective ways to prevent this reaction is to remove the lymphocytes from the transplanted marrow. Unfortunately, without lymphocytes the recipient s immune system will be lowered and may result in a relapse of leukemia or an infection. Researchers have shown they can perform effective BMT by removing the lymphocytes prior to the transplant and then later adding the lymphocytes back. This technique can reduce the potential for GVHD and preserve the graft-versus-leukemia (GVL) effect of the transplant. In this study researchers plan to use peripheral blood with lymphocytes removed rather than bone marrow. In order to increase the number of progenitor cells, the cells responsible for correcting the leukemia, donors will receive doses of G-CSF prior to the transplant. G-CSF (granulocyte colony stimulating factor) is a growth factor that increases the production of progenitor cells in the donor s blood stream. The study will be broken into two parts. The first part of the study will attempt to determine if peripheral blood with lymphocytes removed can prevent GVHD while preserving the GVL effect of the transplant. In the second part of the study, patients that received the transplant will have the lymphocytes added-back on two separate occasions in order reduce the chances of relapse and infection. The study is designed to treat up to 55 patients ages 10 to 60 years and follow their progress for 5 years.

Conditions

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

Keywords

Peripheral Blood Stem Cells; Graft-Versus-Leukemia; Graft vs. Host Disease; Whole Body Irradiation; Donor Apheresis; Cyclophosphamide; Graft-Versus-Myeloma; Leukemic Relapse; Multiple Myeloma; Acute Myelogenous Leukemia (AML); Chronic Myelogenous Leukemia (CML); Acute Lymphoblastic Leukemia (ALL); Myelodysplastic Syndromes; Chronic Lymphocytic Leukemia (CLL)

Outcome Measures

Primary Outcomes (1)

• To evaluate the feasibility of using G-CSF mobilized donor blood to transplant a predetermined dose of stem cells and T lymphocytes to recipients with hematologic malignacies.

Interventions

Allogeneic Bone Marrow Transplant PROCEDURE

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 to 55 years.
• Chronic myelogenous leukemia, any of these categories: chronic phase, accelerated phase of 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 per cu mm, Karyotypes t9;22, t4, t19, t11, biphenotypic leukemia). All second 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 excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia.
• Multiple myeloma following initial disease control with chemotherapy.
• Chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia, in remission or partial remission following fludarabine treatment. Richter transformation of CLL.
• No major organ dysfunction precluding transplantation.
• DLCO greater than 65 percent predicted.
• Left ventricular ejection fraction: greater than 40 percent predicted.
• ECOG performance status of 0 or 1.
• Informed consent given. Informed consent from both parents for minors.
• Women of childbearing age with a negative pregnancy test may participate.

You may not qualify if:

• Pregnant.
• Age greater than 55 or less than 10.
• ECOG performance status of 2 or more.
• Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible.
• Major anticipated illness or organ failure incompatible with survival from BMT.
• DLCO less than 65% predicted.
• Left ventricular ejection fraction: less than 40% predicted.
• Serum creatinine greater than 3 mg/dl.
• Serum bilirubin greater than 4 mg/dl.
• Transaminases greater than 3 x upper limit of normal.
• HIV positive.
• History of other malignancies except basal cell or squamous carcinoma of the skin, positive PAP smear and subsequent negative follow up (patient).
• HLA 6/6 or 5/6 matched sibling donor.
• Fit to receive G-CSF and give peripheral blood stem cells (normal blood count, normotensive, no history of stroke).
• Informed consent given.

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)

• Mavroudis D, Read E, Cottler-Fox M, Couriel D, Molldrem J, Carter C, Yu M, Dunbar C, Barrett J. CD34+ cell dose predicts survival, posttransplant morbidity, and rate of hematologic recovery after allogeneic marrow transplants for hematologic malignancies. Blood. 1996 Oct 15;88(8):3223-9.

  PMID: 8874224 BACKGROUND

• Barrett AJ, Mavroudis D, Tisdale J, Molldrem J, Clave E, Dunbar C, Cottler-Fox M, Phang S, Carter C, Okunnieff P, Young NS, Read EJ. T cell-depleted bone marrow transplantation and delayed T cell add-back to control acute GVHD and conserve a graft-versus-leukemia effect. Bone Marrow Transplant. 1998 Mar;21(6):543-51. doi: 10.1038/sj.bmt.1701131.

  PMID: 9543057 BACKGROUND

• Barrett AJ, Malkovska V. Graft-versus-leukaemia: understanding and using the alloimmune response to treat haematological malignancies. Br J Haematol. 1996 Jun;93(4):754-61. doi: 10.1046/j.1365-2141.1996.d01-1713.x. No abstract available.

  PMID: 8703800 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

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

Condition Hierarchy (Ancestors)

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

Study Officials

• A. John Barrett, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• 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: March 27, 1997
• Primary Completion: January 31, 2008
• Study Completion: August 3, 2017
• Last Updated: December 12, 2019

Record last verified: 2017-08-03

Locations

US (1)