Chronic Lymphocytic LeukemiaPhase 2NCT00001637
Immunosuppressive Preparation Followed by Blood Cell Transplant for the Treatment of Blood Cancers in Older Adults
A Phase 2 study testing Blood cell transplantation 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.
Trial summary
Diseases such as leukemia, lymphoma, and multiple myeloma fall into the category of blood cancers. Some of these conditions can now be cured by bone marrow transplantation (BMT). Read more about this study
- Who is it for?
- Ages 55 to 71 years
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Graft vs Host Disease, Leukemia
- What is being tested?
- Blood cell transplantation
- Type of treatment
- Surgery or procedure
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Sep 1997to 28 Dec 2016
- 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 55 to 71 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages 55-71 years.
- Chronic myelogenous leukemia (CML): chronic phase.
- Acute lymphoblastic leukemia (ALL), all patients in complete or partial remission.
- Acute myelogenous leukemia (AML): AML in first complete or partial remission. Exceptions: AML with good risk karyotypes: AML M3 t(5;17), AML M4Eo (inv. 16), AML t(8;21). All AML in second or subsequent complete remission.
- Myelodyplastic syndromes: refractory anemia with excess of blasts (less than 10%) or early transformation to acute leukemia or Chronic myelomonocytic leukemia.
- Chronic lymphocytic leukemia (CLL) with bulky or progressive disease despite prior treatment with chemotherapy which includes purine analogs.
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- Mantle cell lymphoma.
- Relapsed or progressive non-Hodgkins lymphoma, failing standard treatment approaches and unsuitable for autologous stem cell transplantation.
- No major organ dysfunction precluding transplantation.
- DLCO greater than or equal to 40% predicted.
- Left ventricular ejection fraction: greater than 30% predicted.
- ECOG performance status of 0-2.
- HLA identical family donor, up to 75 years old.
- Fit to receive G-CSF and give peripheral blood stem cells (normal blood count, normotensive, no history of stroke, no history of severe heart disease).
- Informed consent given.
Who cannot join
- Patient or donor pregnant or lactating.
- Patient age less than 55, greater than 71 years.
- ECOG performance status of 3 or more. Psychiatric disorder or mental deficiency of the patient or the donor 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 40% predicted.
- Left ventricular ejection fraction less than 30% predicted.
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- Serum creatinine greater than 2.5 mg/dl.
- Serum bilirubin greater than 4 mg/dl, transaminases greater than 5 times the upper limit of normal.
- HIV positive (donor or recipient). Donors who are positive for HBV, HCV, or HTLV will be used at the discretion of the investigator.
- Other malignant diseases liable to relapse or progress within 5 years.
- Donor unfit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension, history of heart failure or unstable angina, platelet count less than 90,000/cu mm).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Low Intensity Preparative Regimen Followed by HLA-Matched, Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematologic Malignancies in Older Adults
Diseases such as leukemia, lymphoma, and multiple myeloma fall into the category of blood cancers. Some of these conditions can now be cured by bone marrow transplantation (BMT). The ability of BMT to cure these conditions has been credited to the use of high doses of chemotherapy, radiation therapy, and the antileukemia effect of the transplant.
Because the effectiveness of BMT relies on the use of high doses of chemotherapy and total body irradiation (TBI), it is a therapy associated with toxic side effects. These side effects are often deadly and have limited BMT for use in patients under the age of 55.
In this study researchers plan to treat older patients between the ages of 55 to 75 years with blood cell transplants taken from donors who are genetically matched relatives of the patient. In order to decrease the toxic side effects associated with the transplant, researchers will not use chemoradiotherapy. Instead they plan to use intensive immunosuppressive therapy and allow the transplanted cells to take effect.
Read the detailed description
Patients with adult leukemias, non-Hodgkin's lymphoma and multiple myeloma, can now be cured by allogeneic bone marrow transplantation (BMT). This curative effect has been ascribed to the use of high dose chemoradiotherapy and the antileukemia effect of the graft.
The assumption that BMT relies on the myeloablative effect of high dose chemotherapy and total body irradiation (TBI), has largely restricted allogeneic bone marrow transplantation in adults to those under the age of 55 years. Toxicity related mortality increases progressively with age and although some transplant centers carry out BMT in patients up to the age of 60 years, it is generally accepted that treatment related mortality prohibits the use of allogeneic bone marrow transplantation in patients beyond the age of 55 years.
Several in vitro studies have demonstrated the existence of donor-derived CD4 and CD8 positive lymphocytes with specific reactivity for the patients leukemia and a potent graft versus leukemia (GVL) effect. This GVL effect is best seen in patients with relapse CML after bone marrow transplantation where a single infusion of donor lymphocytes can induce complete remission.
In this protocol, we treat older patients between the ages of 55 to 71 years with hematologic disorders with an allogeneic stem cell transplant from an HLA identical sibling, using intensive immunosuppressive regimen without myeloablation in attempts to decrease the transplant related toxicity while preserving the antileukemia effect of the graft. The low intensity nonmyeloablative conditioning regimen will provide adequate immunosuppression to allow stem cell and lymphocyte engraftment. T-cell replete, donor-derived, granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) will be used to establish hematopoietic and lymphoid immune reconstitution. We will add back lymphocytes in patients with less than 75% donor marrow chimerism as an attempt to prevent graft rejection.
The end points of this study are engraftment, degree of donor-host chimerism, incidence of acute and chronic GVHD, transplant related morbidity and mortality as well as survival.
- Conditions
- Chronic Lymphocytic Leukemia, Graft vs Host Disease, Leukemia, Myelodysplastic Syndrome, Myeloid Leukemia
- Being tested
- Blood cell transplantation
- Keywords
- Peripheral Blood Stem Cells, Engraftment, Fludarabine, Nonmyeloablative, Graft-Versus-Leukemia, Graft vs. Host Disease, Cyclophosphamide, Donor Apheresis, Nonmyeloablative Bone Marrow Transplantation, Chronic Myelogenous Leukemia (CML), Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Myelodysplastic Syndromes, Chronic Lymphocytic Leukemia (CLL), Prolymphocytic Leukemia
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Graft vs Host Disease, Leukemia, Myelodysplastic Syndromes, Leukemia, Myeloid, 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.
Blood cell transplantationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of patients with clinically significant acute GHVD (Grade II or higher) following the T depleted PBPC transplant.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start29 Sep 1997
- Primary completion28 Jul 2008
- Study completion28 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 28 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- A. John Barrett, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001637
- Sponsor's protocol ID
- 970202
- Other IDs
- 97-H-0202
- Status last verified
- 28 Dec 2016
- First submitted
- 3 Nov 1999
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Rowe JM, Andersen JW, Mazza JJ, Bennett JM, Paietta E, Hayes FA, Oette D, Cassileth PA, Stadtmauer EA, Wiernik PH. A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood. 1995 Jul 15;86(2):457-62.
PubMed 7605984Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P, O'Brien S, Khouri I, Gajewski J, Mehra R, Claxton D, Andersson B, Beran M, Przepiorka D, Koller C, Kornblau S, Korbling M, Keating M, Kantarjian H, Champlin R. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood. 1997 Jun 15;89(12):4531-6.
PubMed 9192777Schmitz 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
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Intensity Preparative Regimen Followed by HLA-Matched, Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematologic Malignancies in Older Adults
- ClinicalTrials.gov ID
- NCT00001637
- Acronym / sponsor ID
- 970202
- Conditions
- Chronic Lymphocytic Leukemia, Graft vs Host Disease, Leukemia, Myelodysplastic Syndrome, Myeloid Leukemia
- Keywords
- Peripheral Blood Stem Cells, Engraftment, Fludarabine, Nonmyeloablative, Graft-Versus-Leukemia, Graft vs. Host Disease, Cyclophosphamide, Donor Apheresis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 29 Sep 1997
- Primary completion
- 28 Jul 2008 (actual)
- Study completion
- 28 Dec 2016 (actual)
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Diseases such as leukemia, lymphoma, and multiple myeloma fall into the category of blood cancers. Some of these conditions can now be cured by bone marrow transplantation (BMT). The ability of BMT to cure these conditions has been credited to the use of high doses of chemotherapy, radiation therapy, and the antileukemia effect of the transplant.
Because the effectiveness of BMT relies on the use of high doses of chemotherapy and total body irradiation (TBI), it is a therapy associated with toxic side effects. These side effects are often deadly and have limited BMT for use in patients under the age of 55.
In this study researchers plan to treat older patients between the ages of 55 to 75 years with blood cell transplants taken from donors who are genetically matched relatives of the patient. In order to decrease the toxic side effects associated with the transplant, researchers will not use chemoradiotherapy. Instead they plan to use intensive immunosuppressive therapy and allow the transplanted cells to take effect.
Detailed description
Patients with adult leukemias, non-Hodgkin's lymphoma and multiple myeloma, can now be cured by allogeneic bone marrow transplantation (BMT). This curative effect has been ascribed to the use of high dose chemoradiotherapy and the antileukemia effect of the graft.
The assumption that BMT relies on the myeloablative effect of high dose chemotherapy and total body irradiation (TBI), has largely restricted allogeneic bone marrow transplantation in adults to those under the age of 55 years. Toxicity related mortality increases progressively with age and although some transplant centers carry out BMT in patients up to the age of 60 years, it is generally accepted that treatment related mortality prohibits the use of allogeneic bone marrow transplantation in patients beyond the age of 55 years.
Several in vitro studies have demonstrated the existence of donor-derived CD4 and CD8 positive lymphocytes with specific reactivity for the patients leukemia and a potent graft versus leukemia (GVL) effect. This GVL effect is best seen in patients with relapse CML after bone marrow transplantation where a single infusion of donor lymphocytes can induce complete remission.
In this protocol, we treat older patients between the ages of 55 to 71 years with hematologic disorders with an allogeneic stem cell transplant from an HLA identical sibling, using intensive immunosuppressive regimen without myeloablation in attempts to decrease the transplant related toxicity while preserving the antileukemia effect of the graft. The low intensity nonmyeloablative conditioning regimen will provide adequate immunosuppression to allow stem cell and lymphocyte engraftment. T-cell replete, donor-derived, granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) will be used to establish hematopoietic and lymphoid immune reconstitution. We will add back lymphocytes in patients with less than 75% donor marrow chimerism as an attempt to prevent graft rejection.
The end points of this study are engraftment, degree of donor-host chimerism, incidence of acute and chronic GVHD, transplant related morbidity and mortality as well as survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 55 to 71 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Ages 55-71 years.
- Chronic myelogenous leukemia (CML): chronic phase.
- Acute lymphoblastic leukemia (ALL), all patients in complete or partial remission.
- Acute myelogenous leukemia (AML): AML in first complete or partial remission. Exceptions: AML with good risk karyotypes: AML M3 t(5;17), AML M4Eo (inv. 16), AML t(8;21). All AML in second or subsequent complete remission.
- Myelodyplastic syndromes: refractory anemia with excess of blasts (less than 10%) or early transformation to acute leukemia or Chronic myelomonocytic leukemia.
Key exclusion criteria (11 listed)
- Patient or donor pregnant or lactating.
- Patient age less than 55, greater than 71 years.
- ECOG performance status of 3 or more. Psychiatric disorder or mental deficiency of the patient or the donor 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 40% predicted.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood cell transplantation | Procedure or surgery | – |
Primary outcome
The proportion of patients with clinically significant acute GHVD (Grade II or higher) following the T depleted PBPC transplant.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 7605984Rowe JM, Andersen JW, Mazza JJ, Bennett JM, Paietta E, Hayes FA, Oette D, Cassileth PA, Stadtmauer EA, Wiernik PH. A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood. 1995 Jul 15;86(2):457-62.
- Background: PubMed 9192777Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P, O'Brien S, Khouri I, Gajewski J, Mehra R, Claxton D, Andersson B, Beran M, Przepiorka D, Koller C, Kornblau S, Korbling M, Keating M, Kantarjian H, Champlin R. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood. 1997 Jun 15;89(12):4531-6.
- Background: PubMed 7534141Schmitz 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
A. John Barrett, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Blood cell transplantation 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 15 inclusion and 11 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 17 Dec 2019. 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.. 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 NCT00001637, which also lists 3 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 17 Dec 2019.