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Chronic Lymphocytic LeukemiaPhase 2NCT00001873

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

A Phase 2 study testing Isolex 300i plus MoAbs in people with Chronic Lymphocytic Leukemia and Graft vs Host Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 10 to 55 years
What is being tested?
Isolex 300i plus MoAbs
Type of treatment
Medical device
How many people
102 participants
Where
1 siteUnited States
Study dates
22 Feb 1999to 13 Jun 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 to 55 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
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  • 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.
  • 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).
  • 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.

Who cannot join

  • 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.
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  • 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).
  • Pregnant or lactating.
  • Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible.
  • HIV positive.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed by T-Cell Add-Back for Hematological Malignancies - Role of Cyclosporine

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.

Read more

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

Patients undergoing these experimental techniques must be monitored closely to see if any benefit or harmful effects will occur. Information gathered from this study can be used to develop further research studies and potential new therapies for hematologic malignancies.

Read the detailed description

Bone marrow stem cell transplant studies carried out by the NHLBI BMT Unit have focused on approaches to optimize the stem cell and lymphocyte dose in order to improve transplant survival and increase the graft-vs.-leukemia effect. A CD34 stem cell dose of greater than 3 x 10(6)/kg was found to increase survival and reduce relapse, while a CD3+ lymphocyte dose of less than 1 x 10(5)/kg was associated with a very low incidence of GVHD. Although processing of 2 peripheral blood progenitor cell (PBPC) collections with the CellPro immunoabsorption method (combined CD34-positive selection and CD2-negative selection) provided an improvement over previous methods, the system did not always achieve these optimal cell doses. A recent preclinical evaluation by the Department of Transfusion Medicine of a new immunomagnetic cell selection system available from Nexell, Inc. has demonstrated improved recovery of CD34+ cells and increased depletion of T lymphocytes, compared to the CellPro method. Incorporation of the Nexell system (Isolex 300i) into this clinical protocol will allow us to more consistently achieve CD34+ cell doses above the threshold of 3 x 10(6)/kg and CD3+ lymphocyte dosing in the region of 0.5 x 10(5)/kg. This will make it possible to test (1) the potential benefit of optimized transplant cell doses, (2) elimination of post transplant immunosuppression to enhance immune recovery.

In this study, we will use the Nexell Isolex 300i system to obtain more data on the relationship between CD34+ stem cell dose and outcome. In recipients who receive a T cell dose less than 0.5 x 10(5) CD3+ cells/kg the effect of withdrawing cyclosporine on development of GVHD will be evaluated in a cohort study: 20 patients will receive low dose cyclosporine. If the incidence of grade II or worse GVHD is 10% or less, no post transplant immunosuppression will be given to the next cohort and the incidence and severity of acute GVHD again assessed. Stopping rules for unacceptable GVHD severity will be applied. Two match groups HLA 6/6 and 5/6 donor-recipient pairs will be separately studied using this approach.

In a second phase of the study we will continue to accumulate data on T lymphocyte add-back given on day 45 and day 100 after transplant. For this phase, cyclosporine will be reintroduced on day 44 and continued until day 120 to accelerate immune recovery.

Up to 70 patients aged between 10 and 55 years will be studied in each subset (HLA 6/6 and 5/6 matched cohorts). The major endpoint of the study is acute GVHD after transplant. We will also measure engraftment, acute and chronic GVHD, leukemic relapse, transplant-related and all causes of mortality, cytomegalovirus reactivation and leukemia-free survival. Patients will be followed for a minimum of 5 years.

Being tested
Isolex 300i plus MoAbs
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
Medical subject headings
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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Isolex 300i plus MoAbsDevice

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Day 45

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 1999 (estimated)
  2. Study start22 Feb 1999
  3. Primary completion28 Dec 2007
  4. Study completion13 Jun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
102 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00001873
Sponsor's protocol ID
990046
Other IDs
99-H-0046
Status last verified
13 Jun 2017
First submitted
3 Nov 1999
Last updated
26 Sep 2018
Results posted
No

Publications

  • 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.

    PubMed 7534141
  • 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.

    PubMed 7534140
  • 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.

    PubMed 8991536
  • 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.

    PubMed 23524640
  • 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.

    PubMed 23065508

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Isolex 300i plus MoAbs in people with Chronic Lymphocytic Leukemia and Graft vs Host Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The proportion of patients with clinically significant acute GHVD (Grade II or higher) following the T depleted PBPC transplant (and before D45 add-back). (time frame: Day 45). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00001873, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2018.

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