HEMATOLOGIC MALIGNANCIESTLINCT01081405
Total Lymphoid Irradiation and Anti-Thymocyte Globulin in the Allogeneic Hematopoietic Cell Transplantation
A study testing TOTAL LYMPHOID IRRADIATION in people with HEMATOLOGIC MALIGNANCIES, run by Fondazione EMN Italy Onlus at 1 site in Italy.
Trial summary
To exploit the curative potential of allografting, the ultimate clinical goal is to separate GVL from GVHD. In murine preclinical models, recipients of allogeneic hematopoietic cell transplants after a preparative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) did not develop GVHD. Read more about this study
- Who is it for?
- Ages 50 to 70 years
- Conditions the study is for
- HEMATOLOGIC MALIGNANCIES
- What is being tested?
- TOTAL LYMPHOID IRRADIATION
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- Nov 2007to Nov 2022
- Phase
- Interventional
- 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 50 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any patient with one of the following hematolymphoid malignancies or syndromes in whom allogeneic NST is warranted. Specific disease categories include: indolent advanced stage Non-Hodgkin Lymphomas, Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, Hodgkin Disease, Acute Leukemias in any complete remission, Aplastic Anemia, Paroxsymal Nocturnal Hemoglobinuria, Myelodysplastic and Chronic Myeloproliferative Syndromes, Multiple Myeloma. Patients with other selected malignancies/disorders may also be considered but must be approved by the transplant team and the Principal Investigator.
- Elderly patients age > 50 < 70 years, or for patients <50 years of age but because of pre-existing medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional myeloablative transplants, or because of refusal to undergo conventional myeloablative regimes.
- A fully HLA-identical sibling or matched unrelated donor is available. Patients with one antigen mismatched donors can be considered but only after discussion with the transplant team and the Principal Investigator.
- Patient must be competent to give consent.
Who cannot join
- Patients with progressive hematolymphoid malignancies despite conventional therapies, or acute leukemias not in complete remission.
- Uncontrolled CNS involvement with disease
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
- Females who are pregnant
- Organ dysfunction defined as follows:
- Cardiac function: ejection fraction <30% or uncontrolled cardiac failure
Show all 14Show fewer
- Pulmonary: DLCO <40% predicted
- Liver function abnormalities: elevation of bilirubin to > 3 mg/dl and/or transaminases >4x the upper limit of normal
- Renal: creatinine clearance <50 cc/min (24 hour urine collection)
- Karnofsky performance score < 60%
- Patients with poorly controlled hypertension on multiple antihypertensives
- Documented fungal disease that is progressive despite treatment
- Viral infections: HIV positive patients. Hepatitis B and C positive patients will be evaluated on a case by case basis
- Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or Principal Investigator would place the patient at unacceptable risk from this regimen.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Allogeneic Hematopoietic Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Patients With Hematologic Malignancies
To exploit the curative potential of allografting, the ultimate clinical goal is to separate GVL from GVHD. In murine preclinical models, recipients of allogeneic hematopoietic cell transplants after a preparative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) did not develop GVHD. The murine TLI/ATG study was turned into a clinical phase I protocol for patients with hematological malignancies, and a reduction of acute GVHD to < 3% was observed (Lowsky R et al, N Engl J Med). This suggests that specific immune mechanisms control GVHD and preserve GVL. The study will include patients with lympho and myeloproliferative diseases. The conditioning regimen will consist of TLI [ten 80 cGy fractions on day -11 through day -7 and on day -4 through day -1; the radiation field (four fields-two anterior and two posterior) involves all major lymphoid organs including the thymus, spleen and lymph nodes] and ATG (five i.v. doses at 1.5 mg/kg/day from day -11 through day -7). G-CSF mobilised hematopoietic cells, collected on days -1 and 0, from HLA-identical siblings or unrelated donors will be infused on day 0. Post-transplant immunosuppression will consist of oral cyclosporine (at 6.25 mg/kg/d) from day -3 and micophenolate mophetile (at 15 mg/Kg bid) from day +1. The clinical primary objective is to reduce the incidence of GVHD to < 5%, with better survival and quality of life.
Read the detailed description
PATIENT ENROLMENT.
It is expected that about 15 patients / year will be enrolled in this phase I-II protocol. Patient selection will be based on the following criteria:
Eligibility Criteria:
- Any patient with one of the following lympho or myeloproliferative malignancies or syndromes in whom allogeneic NST is warranted. Patients with other selected malignancies/disorders may also be considered but must be approved by the transplant team and the Principal Investigator.
- Patient age > 50 years, or for patients <50 years of age but because of pre-existing medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional myeloablative transplants.
- an HLA-identical sibling or matched unrelated donor is available. Patients with one antigen mismatched donors can be considered but only after discussion with the transplant team and the Principal Investigator.
STEM CELL TRANSPLANTATION:
(A) TLI Administration: see "brief description" (B) ATG: Thymoglobulin will be administered five times intravenously at 1.5 mg/kg/day from day -11 through day -7 for a total dose of 7.5 mg/kg. Thymoglobulin doses will be based on the adjusted ideal body weight. Premedication for thymoglobulin will include solumedrol 1.0 mg/kg.
Mobilized PBPC: The minimum cell doses (based on recipient body weight) for transplants are > 5x106 CD34+ cells/kg. Cells collected on days -1 and 0 will be pooled and processed for infusion on day 0. Fresh cells (not frozen) are to be infused. For related donor transplants, if the target cell dose is not achieved then a third apheresis procedure may be performed on day+1 and the cells infused on the same day. Collection of cells for unrelated donor transplants will be coordinated through the Italian bone Marrow Transplant Registry and subject to the rules of that Program. If mobilized PBPC is not available through certain collection centers then bone marrow will be used.
(F) Cyclosporine (CSP): CSP is given at 6.25 mg/kg p.o. b.i.d (9 a.m and 9 p.m.) from day -3 until after the day +56 chimerism results are obtained. CSP will be tapered after the day +56 chimerism results are obtained. If the day +56 chimerism results show >40% donor cells in the CD3+ lineage, and the patient is without evidence of GVHD then CSP taper will begin. The CSP will be tapered at 6% every week. Modifications of the taper schedule may be indicated if significant disease progression occurs early post-transplantation or the patient develops GVHD.
(G) Mycophenylate mofetil (MMF): Administration of MMF will begin at 15 mg/kg po on day 0, at 5-10 hours after mobilized PBPC infusion is complete. Thereafter,beginning on day +1 MMF is taken at 15 mg/kg po b.i.d. (30 mg/kg/day) if transplantation was using a matched related donor and 15 mg/kg po t.i.d if from a matched unrelated donor or a one antigen mismatched donor. Doses will be rounded up to the nearest 250 mg (capsules are 250 mg). MMF will be stopped on day +28 for matched related donors and for one antigen mismatched or unrelated donors beginning day +40 MMF will be tapered by 10% weekly till off, typically by day +96.
POST-TRANSPLANT FOLLOW-UP
Clinical: The incidence, severity and extent of acute and chronic GVHD will be monitored and scored according to standard criteria. As well, documented and presumed post-transplant infectious complications, rate of relapse, event-free and overall survival and transplant related mortality will be recorded.
Assessment of Disease Response: Since the diseases treated on this protocol are heterogenous, appropriate disease specific studies will be performed to evaluate response to transplant. Responses will be classified as continued complete remission (CCR), achieved complete remission (CRa), partial response (PR), progressive disease (PD), or no response (NR). Disease response will be according to accepted criteria. All cases of progressive disease should be discussed with the Principal Investigators. If patients show evidence of progressive disease then they may be candidates for donor lymphocyte infusion.
- Conditions
- HEMATOLOGIC MALIGNANCIES
- Being tested
- TOTAL LYMPHOID IRRADIATION
- Keywords
- ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION, TOTAL LYMPHOID IRRADIATION, ANTI-THYMOCYTE GLOBULIN
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TOTAL LYMPHOID IRRADIATIONOther
Allogeneic Hematopoietic Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Patients with Hematologic Malignancies
| Study group | Role | What they receive |
|---|---|---|
| TOTAL LYMPHOID IRRADIATION | Experimental | Allogeneic Hematopoietic Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Patients with Hematologic Malignancies Receives: Other: TOTAL LYMPHOID IRRADIATION |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Outcome Measure not applicable
Measured: Not reached
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2010 (estimated)
- Study startNov 2007
- Primary completionNov 2022
- Study completionNov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HEMATOLOGIC MALIGNANCIESStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione EMN Italy Onlus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01081405
- Sponsor's protocol ID
- TLI-001-2007
- Other IDs
- 2007-005563-10
- Acronym
- TLI
- Status last verified
- Mar 2024
- First submitted
- 2 Mar 2010
- Last updated
- 13 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Hematopoietic Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Patients With Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT01081405
- Acronym / sponsor ID
- TLI / TLI-001-2007
- Conditions
- HEMATOLOGIC MALIGNANCIES
- Keywords
- ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION, TOTAL LYMPHOID IRRADIATION, ANTI-THYMOCYTE GLOBULIN
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Fondazione EMN Italy OnlusUniversity, hospital or other
- Study start
- Nov 2007 (actual)
- Primary completion
- Nov 2022 (actual)
- Study completion
- Nov 2022 (actual)
- First posted
- 5 Mar 2010 (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.
To exploit the curative potential of allografting, the ultimate clinical goal is to separate GVL from GVHD. In murine preclinical models, recipients of allogeneic hematopoietic cell transplants after a preparative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) did not develop GVHD. The murine TLI/ATG study was turned into a clinical phase I protocol for patients with hematological malignancies, and a reduction of acute GVHD to < 3% was observed (Lowsky R et al, N Engl J Med). This suggests that specific immune mechanisms control GVHD and preserve GVL. The study will include patients with lympho and myeloproliferative diseases. The conditioning regimen will consist of TLI [ten 80 cGy fractions on day -11 through day -7 and on day -4 through day -1; the radiation field (four fields-two anterior and two posterior) involves all major lymphoid organs including the thymus, spleen and lymph nodes] and ATG (five i.v. doses at 1.5 mg/kg/day from day -11 through day -7). G-CSF mobilised hematopoietic cells, collected on days -1 and 0, from HLA-identical siblings or unrelated donors will be infused on day 0. Post-transplant immunosuppression will consist of oral cyclosporine (at 6.25 mg/kg/d) from day -3 and micophenolate mophetile (at 15 mg/Kg bid) from day +1. The clinical primary objective is to reduce the incidence of GVHD to < 5%, with better survival and quality of life.
Detailed description
PATIENT ENROLMENT.
It is expected that about 15 patients / year will be enrolled in this phase I-II protocol. Patient selection will be based on the following criteria:
Eligibility Criteria:
- Any patient with one of the following lympho or myeloproliferative malignancies or syndromes in whom allogeneic NST is warranted. Patients with other selected malignancies/disorders may also be considered but must be approved by the transplant team and the Principal Investigator.
- Patient age > 50 years, or for patients <50 years of age but because of pre-existing medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional myeloablative transplants.
- an HLA-identical sibling or matched unrelated donor is available. Patients with one antigen mismatched donors can be considered but only after discussion with the transplant team and the Principal Investigator.
STEM CELL TRANSPLANTATION:
(A) TLI Administration: see "brief description" (B) ATG: Thymoglobulin will be administered five times intravenously at 1.5 mg/kg/day from day -11 through day -7 for a total dose of 7.5 mg/kg. Thymoglobulin doses will be based on the adjusted ideal body weight. Premedication for thymoglobulin will include solumedrol 1.0 mg/kg.
Mobilized PBPC: The minimum cell doses (based on recipient body weight) for transplants are > 5x106 CD34+ cells/kg. Cells collected on days -1 and 0 will be pooled and processed for infusion on day 0. Fresh cells (not frozen) are to be infused. For related donor transplants, if the target cell dose is not achieved then a third apheresis procedure may be performed on day+1 and the cells infused on the same day. Collection of cells for unrelated donor transplants will be coordinated through the Italian bone Marrow Transplant Registry and subject to the rules of that Program. If mobilized PBPC is not available through certain collection centers then bone marrow will be used.
(F) Cyclosporine (CSP): CSP is given at 6.25 mg/kg p.o. b.i.d (9 a.m and 9 p.m.) from day -3 until after the day +56 chimerism results are obtained. CSP will be tapered after the day +56 chimerism results are obtained. If the day +56 chimerism results show >40% donor cells in the CD3+ lineage, and the patient is without evidence of GVHD then CSP taper will begin. The CSP will be tapered at 6% every week. Modifications of the taper schedule may be indicated if significant disease progression occurs early post-transplantation or the patient develops GVHD.
(G) Mycophenylate mofetil (MMF): Administration of MMF will begin at 15 mg/kg po on day 0, at 5-10 hours after mobilized PBPC infusion is complete. Thereafter,beginning on day +1 MMF is taken at 15 mg/kg po b.i.d. (30 mg/kg/day) if transplantation was using a matched related donor and 15 mg/kg po t.i.d if from a matched unrelated donor or a one antigen mismatched donor. Doses will be rounded up to the nearest 250 mg (capsules are 250 mg). MMF will be stopped on day +28 for matched related donors and for one antigen mismatched or unrelated donors beginning day +40 MMF will be tapered by 10% weekly till off, typically by day +96.
POST-TRANSPLANT FOLLOW-UP
Clinical: The incidence, severity and extent of acute and chronic GVHD will be monitored and scored according to standard criteria. As well, documented and presumed post-transplant infectious complications, rate of relapse, event-free and overall survival and transplant related mortality will be recorded.
Assessment of Disease Response: Since the diseases treated on this protocol are heterogenous, appropriate disease specific studies will be performed to evaluate response to transplant. Responses will be classified as continued complete remission (CCR), achieved complete remission (CRa), partial response (PR), progressive disease (PD), or no response (NR). Disease response will be according to accepted criteria. All cases of progressive disease should be discussed with the Principal Investigators. If patients show evidence of progressive disease then they may be candidates for donor lymphocyte infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TOTAL LYMPHOID IRRADIATION | Experimental | Other: TOTAL LYMPHOID IRRADIATIONAllogeneic Hematopoietic Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Patients with Hematologic Malignancies |
Who may qualify
- Ages
- 50 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Any patient with one of the following hematolymphoid malignancies or syndromes in whom allogeneic NST is warranted. Specific disease categories include: indolent advanced stage Non-Hodgkin Lymphomas, Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, Hodgkin Disease, Acute Leukemias in any complete remission, Aplastic Anemia, Paroxsymal Nocturnal Hemoglobinuria, Myelodysplastic and Chronic Myeloproliferative Syndromes, Multiple Myeloma. Patients with other selected malignancies/disorders may also be considered but must be approved by the transplant team and the Principal Investigator.
- Elderly patients age > 50 < 70 years, or for patients <50 years of age but because of pre-existing medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional myeloablative transplants, or because of refusal to undergo conventional myeloablative regimes.
- A fully HLA-identical sibling or matched unrelated donor is available. Patients with one antigen mismatched donors can be considered but only after discussion with the transplant team and the Principal Investigator.
- Patient must be competent to give consent.
Key exclusion criteria (14 listed)
- Patients with progressive hematolymphoid malignancies despite conventional therapies, or acute leukemias not in complete remission.
- Uncontrolled CNS involvement with disease
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
- Females who are pregnant
- Organ dysfunction defined as follows:
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 |
|---|---|---|
| TOTAL LYMPHOID IRRADIATIONAllogeneic Hematopoietic Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Patients with Hematologic Malignancies | Other | TOTAL LYMPHOID IRRADIATION |
Primary outcome
Primary Outcome Measure not applicable
Time frame: Not reached
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 13 Mar 2024.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TOTAL LYMPHOID IRRADIATION in people with HEMATOLOGIC MALIGNANCIES, run by Fondazione EMN Italy Onlus at 1 site in Italy.
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 4 inclusion and 14 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 13 Mar 2024. 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 Italy. 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.
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?
Primary Outcome Measure not applicable (time frame: Not reached). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2024.