Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Neoplasms by Histologic Type

Hematologic Diseases

Translocation, Genetic

Chromosome Aberrations

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Micronutrients

Anticoagulants

Blood Substitutes

Hematinics

Antibodies

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Iron

Immunoglobulins

Busulfan

Dextrans

Iron-Dextran Complex

Patients with chronic myeloid leukemia suitable for allogeneic stem cell transplantation with a matched related donor.

Patients were conditioned with oral busulfan 12mg/kg (days -6 to -4), cyclophosphamide 120mg/kg (days -3,-2), rabbit antithymocytic globulin, (Fresenius, Bad Hamburg, Germany) 25mg/kg (days -5 to -1) and fludarabine 200 mg/kg (days -7 to-3). CD34 cells were positively selected using anti-CD34 antibody conjugated to iron-dextran microbeads using CliniMACS device (Miltenyi Biotech, Bergisch Gladbach, Germany) with an aim to collect \> 5.0 x 106 CD34 cells/kg. DLI was administered in escalating dose regimen starting from 3 x 106 cells/kg followed as necessary by 1 x 107 cells/kg, 5 x 107 cells/kg and 1 x 108 cells/kg.

Stem cell transplantation

Jacob M Rowe, MD

Allogeneic stem cell transplantation, the only known curative modality for CML, was abandoned in recent years for a very effective and much less toxic targeted therapy with the tyrosine kinase inhibitors (TKIs). However, approximately one third of patients still need another treatment including stem cell transplantation. The study protocol comprised a cohort of consecutive patients with CML who received allogeneic stem cell transplantation using partial T cell depletion, with no post-transplant GvHD prophylaxis. Forty consecutive patients with CML underwent allogeneic stem cell transplantation from a matched sibling using partial T cell depletion (TCD), in a single institution. Escalated dose of donor lymphocyte infusion (DLI) was given in case of either relapse or presence of minimal residual disease (MRD) as detected by cytogenetic or molecular analysis.

The purpose of the study is to decrease transplant-related toxicity.

Patients were conditioned with oral busulfan 12mg/kg (days -6 to -4), cyclophosphamide 120mg/kg (days -3,-2), rabbit antithymocytic globulin, (Fresenius, Bad Hamburg, Germany) 25mg/kg (days -5 to -1) and fludarabine 200 mg/kg (days -7 to-3). Final busulfan dose was individually determined based on measurements of serum busulfan levels with a target dose of 850-1400 microM x minute.

Transplants were performed in reverse isolation rooms equipped with high-efficiency particulate air filtration systems (HEPA). No post-transplant GvHD prophylaxis was given. Post-transplant infection prophylaxis consisted of acyclovir, itraconazole, trimethoprim-sulfamethoxazole and penicillin VK. Cytomegalovirus (CMV) status was determined weekly using PCR for CMV-DNA and pp65 antigenemia in blood leukocytes, followed by preemptive ganciclovir administration when positive.

Donors Donors were human leukocyte antigen (HLA) A,B,C serologically matched and DR and DQ molecularly matched siblings. Donor stem cells were collected following mobilization with 10 µg/kg/day G-CSF, given subcutaneously for 5 consecutive days. CD34 cells were positively selected using anti-CD34 antibody conjugated to iron-dextran microbeads using CliniMACS device (Miltenyi Biotech, Bergisch Gladbach, Germany) with an aim to collect \> 5.0 x 106 CD34 cells/kg.

Disease monitoring Following transplant, all patients were under close surveillance for the presence of minimal residual disease (MRD) using cytogenetic analysis and PCR for the detection of BCR/ABL transcripts. Bone marrow and peripheral blood samples were examined every 3 months in the first year post transplant and every 3-6 months in the subsequent years.

PCR method: RQ-PCR was performed according to the Europe Against Cancer (EAC) protocol.19 The BCR-ABL and ABL copy numbers were calculated by comparing with the standard curve generated using IPSOGEN FusionQuant Standards. The results of quantifying BCR-ABL transcripts were expressed as percentage ratios relative to total ABL transcripts.

A minimum number of 1x104 copies of ABL is the lower limit below which a negative RT-PCR was considered unreliable. In the molecular biology laboratory of the Rambam Health Care Campus the sensitivity for quantitative Q-PCR is (10-5).

Donor leukocyte infusion (DLI). DLI was administered in escalating dose regimen starting from 3 x 106 cells/kg followed as necessary by 1 x 107 cells/kg, 5 x 107 cells/kg and 1 x 108 cells/kg.

DLI was used in case of persistence/reappearance of BCR-ABL transcripts starting from 6 months post transplant onward. In instances where more than 1 DLI was administered the successive escalated dose was given at ≥ 3-month intervals as dictated by MRD follow-up.

Allogeneic Stem Cell Transplantation in CML With Partial T Cell Depletion

Allogeneic Stem Cell Transplantation in CML With Partial T Cell Depletion and Preemptive Donor Lymphocyte Infusion.

Miltenyi Biomedicine GmbH

Rambam Health Care Campus

Tsila Zuckerman, MD

Immune System Diseases

Syndrome

Lymphoma

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myeloid, Acute

Leukemia, Lymphocytic, Chronic, B-Cell

Preleukemia

Myelodysplastic Syndromes

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Myeloid Leukemia

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Chronic Lymphocytic Leukemia

Acute Graft Versus Host Disease

Melphalan

Thymoglobulin

Thiotepa

Antilymphocyte Serum

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

CD34 peripheral blood progenitor cell (PBPC) transplants in 3 groups: 1) HLA-matched Sibling Transplant Patients; 2) Unrelated Donor Transplant Patients; 3) Haplo Identical Transplant Patients. Preparative regimen is 140 mg/m\^2 Melphalan on day -8, 10 mg/kg Thiotepa on day -7, 160 mg/m\^2 Fludarabine over 4 days on days -6, -5, -4, -3 and 1.5 mg/kg of Rabbit ATG a day times 4 over 4 days on days -6, -5, -4, -3.

Haploidentical peripheral blood progenitor cell (PBPC) transplants on Day 0.

Megadose of CD34 Selected Progenitor Cells

160 mg/m\^2 over 4 days on days -6, -5, -4, -3

1.5 mg/kg of Rabbit ATG a day times 4 over 4 days on days -6, -5, -4, -3.

Rabbit ATG

Richard E. Champlin, MD

Donor:

This clinical study will evaluate the feasibility of a purified CD34 peripheral blood progenitor cell (PBPC) transplants in patients with hematological malignancies.

The primary objectives of the study are to evaluate the recipient obtaining donor derived neutrophil engraftment and the incidence of acute graft versus host disease \[GvHD\] (grade III-IV).

Secondary objectives include assessments of recipient having donor derived platelet engraftment, incidence of graft failure and chronic GvHD, overall and disease free survival, clinical safety and device performance of the CliniMACS CD34 selection device.

Donor Description:

Before taking part in this study, donors will have an evaluation that is the standard for any bone marrow or blood stem cell donor. These include standard blood tests, an electrocardiogram (EKG), and a chest X-ray. Donors will also be given a general health questionnaire that is given to all blood donors in the United States. It should take no more than 10 minutes to complete the questionnaire.

Donors in this study will receive standard mobilization therapy with daily G-CSF every 12 hours. The Granulocyte colony-stimulating factor (G-CSF) will be given as an injection under the skin. The mobilization phase starts on the first day that donors receive G-CSF and continues until the final day of the stem cell collection process (leukapheresis).

Donors in this study will receive Neupogen (white blood cell growth factor) to stimulate the immature blood cells. They will receive two injections, twice a day for four days. On the fourth day, assuming they have enough immature white blood cells, researchers will start the stem cell collection process (leukapheresis).

The stem cell collection will go from 1 to 4 days until enough immature cells have been collected, but will not be done on any day the donor's platelet count falls below 75,000. The stem cell is called a CD34(+) cell. These cells will then be processed over a cell-processing machine to try to purify the immature fraction of cells and remove the T-lymphocytes that are part of the fatal graft versus host disease. The T-cell is called a CD3(+) cell.

Leukapheresis, with later CD34(+) cell selection, will start on the day when circulating CD34(+) count is at a high enough level. Leukapheresis will continue until the appropriate count is reached. If the CD3(+) count is too high, adjustments will be made.

For those donors who cannot reach the collection goal in one series of collection attempts, researchers will wait until the donor recovers from the first stem cell collection and try again. If the donor is unable to reach the collection goal again, another attempt will be made with a different donor.

The blood thinner used for the procedure will be acid citrate dextrose (ACD). Heparin may be substituted when clinically needed. No additional blood thinners or additives should be added beyond those normally used during leukapheresis. A unique identification and labeling system shall be used to track the leukapheresis product from collection to infusion.

Samples will be taken from each leukapheresis product pre- and post-selection for quality analysis.

This is an investigational study. No more than 90 donors will take part in this study. All will be enrolled at M. D. Anderson.

Recipient Description:

Before taking part in this study, recipients will have standard evaluations to determine the stage of their disease. These may include bone marrow aspirations and biopsies and if necessary, CT scans and chest x-rays. All recipients will go through cardiopulmonary evaluation.

The recipients will have an allogeneic bone marrow transplant with pre-treatment of thiotepa, fludarabine, melphalan, and antithymocyte globulin. This will be followed by infusion of the peripheral blood progenitor cells.

Recipients will have daily follow-up exams in the hospital. Recipients will be evaluated at least one to five times per week after they leave until Day 100. After that, they will have evaluations at least once every three months until about one year and then once every six months.

The CliniMACS device is being provided by used of an investigational device exemption for the FDA. Without the CliniMACS device, this procedure would not be possible.

This is an investigational study. A total of 40 patients will take part in this study. All will be enrolled at M. D. Anderson.

Megadose CD34 Selected Progenitor Cells for Transplantation in Patients With Advanced Hematological Malignant Diseases

Absolute neutrophil engraftment defined as first of 3 consecutive days with Absolute neutrophil count (ANC) equal to or more than 0.5 \* 10\^9/L. Baseline to Day 30 post transplant.

M.D. Anderson Cancer Center

Melphalan 140 mg/m\^2 given IV for one day. Thiotepa 10 mg/kg given IV for one day. Fludarabine 40 mg/m\^2 given IV daily for four days. Rabbit ATG 1.5 mg/kg given IV daily for four days. Stem Cell Infusion of CD34+ Selected Cells given on Day 0.

CD34 PBPC

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Richard E. Champlin

Melphalan 140 mg/m\^2 given for one day. Thiotepa 10 mg/kg given for one day. Fludarabine 40 mg/m\^2 given daily for four days. Rabbit ATG 1.5 mg/kg given daily for four days. Infusion of CD34+ Selected Cells given on Day 0.

Melphalan + Thiotepa + Fludarabine + Rabbit ATG + CD34 PBPC

Number of Participants With Absolute Neutrophil Count Engraftment

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Allogeneic Stem Cell Transplantation in CML With Partial T Cell Depletion	NCT00966810	Philadelphia Ch...	Stem cell trans...	18 Years - 65 Years	Rambam Health Care Campus
Megadose CD34 Selected Progenitor Cells for Transplantation in Patients With Advanced Hematological Malignant Diseases	NCT00038857	Leukemia Lymphoma	Megadose of CD3... Melphalan Thiotepa Fludarabine Rabbit ATG	- 55 Years	M.D. Anderson Cancer Center
Allogeneic Stem Cell Transplantation in CML With Partial T Cell Depletion	NCT00966810	Philadelphia Ch...	Stem cell trans...	18 Years - 65 Years	Rambam Health Care Campus

Spots Global Cancer Trial Database for t cell depletion