LymphomaPhase 2NCT00113828
Non-Myeloablative HLA-Matched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies
A Phase 2 study testing Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant and T-cell depleted peripheral blood stem cell transplant in people with Lymphoma and Leukemia, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The purpose of this trial is to determine if patients with hematologic diseases who have a HLA 6/6 matched related donor and are not eligible for a standard myeloablative stem cell transplant will have less severe graft versus host disease (GVHD), transplant related mortality, and less graft failure when treated with… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Lymphoma, Leukemia, Multiple Myeloma
- What is being tested?
- Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant and T-cell depleted peripheral blood stem cell transplant
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2004to Mar 2007
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Disease statue: NHL, HD, or MM that are chemorefractory or relapsed; CLL that is Rai Stage III/IV, or lymphocyte doubling time of 6 months, or stage I/II that is resistant to > 2 chemotherapy regimens; AML or ALL in 1st or subsequent remission with poor prognostic features; CML in accelerated or blast phae; MDS with life-threatening cytopenias; patients who have had a previous autologous or allogeneic bone marrow or stem cell transplant; other hematologic disorders which allogeneic stem cell transplantation is appropriate where the risk of conventional transplantation is considered to be unacceptably high.
- Estimated disease-free survival of less than one year
- ECOG performance status of 0, 1, or 2
- HLA-genotypically or phenotypically matched (at A, B, DR loci) related donor
Who cannot join
- Patients who life expectancy is limited by diseases other than their hematologic malignancy.
- Cardiac Disease: symptomatic congestive hearth failure, or RVG, or ejection fraction of < 45%, active angina pectoris, or uncontrolled hypertension.
- Pulmonary Disease: severe chronic obstructive lung disease, or symptomatic restrictive lung disease, or DLCO of < 50%.
- Renal Disease: serum creatinine > 2.0 mg/dl or creatinine clearance < 50 ml/min.
- Hepatic Disease: serum bilirubin > 2.0 mg/dl or alkaline phosphatase, SGOT or SGPT > 3 times normal.
- Neurologic Disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation
- HIV or HTLV I antibody or Hepatitis B surface antigen positivity
- Uncontrolled infection
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
The purpose of this trial is to determine if patients with hematologic diseases who have a HLA 6/6 matched related donor and are not eligible for a standard myeloablative stem cell transplant will have less severe graft versus host disease (GVHD), transplant related mortality, and less graft failure when treated with a non-myeloablative T-cell depleted stem cell transplant.
Read the detailed description
Our prior experience in the lab and in clinical trials with non-myeloablative HLA-matched and mismatched transplant strategies have been remarkable for a low transplant related mortality rate, but a still formidable risk of GVHD and graft rejection. In this trial, we have incorporated a combination ex-vivo T-cell depletion strategy to prevent GVHD with vigorous in vivo depletion of host (and to a lesser extent donor) T-cells to prevent graft rejection.
Patients will receive non-myeloablative conditioning with cyclophosphamide, thymoglobulin, fludarabine, and thymic irradiation, followed by a T-cell depleted PBSC infusion. Cyclosporine will be given for GVHD prophylaxis, and tapered beginning on day 35. Data from our mouse model and previous clinical trials have demonstrated that this approach can induce mixed chimerism without GVHD, with the potential for conversion of mixed chimerism to full donor hematopoiesis following donor leukocyte infusions.
- Conditions
- Lymphoma, Leukemia, Multiple Myeloma, Myelodysplastic Syndrome
- Being tested
- Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant, T-cell depleted peripheral blood stem cell transplant
- Keywords
- Non-Myeloablative, Stem Cell Transplantation, T-cell Depletion, HLA-Matched
- Medical subject headings
- Lymphoma, Leukemia, Multiple Myeloma, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-myeloablative Ex-Vivo T-cell Depleted PBSC TransplantProcedure or surgery
Also called Cyclosporine iv beginning on transplant day -1
Rabbit anti-thymocyte globulin 0.5 mg/kg on transplant day-8, 2.5 mg/kg on day-7 and 3.0 mg/kg on day-6; cyclophosphamide 60 mg/kg on days-7,-6; fludarabine 25 mg/m2 on days -5, -4, -3, -2, -1.
Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant.
T-cell depleted peripheral blood stem cell transplantProcedure or surgery
Also called Cyclosporine iv beginning on day -1.
Rabbit anti-thymocyte globulin 0.5 mg/kg on transplant day-8, 2.5 mg/kg on day-7, 3.0 mg/kg on day-6; cyclophosphamide 60 mg/kg on days -7, -6; fludarabine 25 mg/m2 on days -5 through -1.
T-cell depleted peripheral blood stem cell transplant .
| Study group | Role | What they receive |
|---|---|---|
| Transplantation | Experimental | T-cell depleted HLA-matched peripheral blood stem cell transplantation Receives: Procedure: Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant; Procedure: T-cell depleted peripheral blood stem cell transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the risks of severe (grade III/IV) GVHD or transplant related mortality at < 100 days following HLA-matched non-myeloablative stem cell transplantation (or following "prophylactic" DLI given for chimerism conversion).
Measured: 100 days
Secondary outcomes (3)
To evaluate the incidence of acute and chronic GVHD.
Measured: indefinite
To evaluate the incidence of graft loss.
Measured: 100 days
To evaluate progression free and overall survival.
Measured: indefinite
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2005 (estimated)
- Study startDec 2004
- Primary completionMar 2007
- Study completionMar 2007
Why it stopped: Insufficient accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute
- Responsible party
- Principal investigator, Thomas Spitzer, Massachusetts General Hospital
- Investigators
- Thomas Spitzer, M.D., Principal investigator, Massachusetts General Hospital, Harvard University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00113828
- Sponsor's protocol ID
- 04-222
- Status last verified
- Mar 2018
- First submitted
- 10 Jun 2005
- Last updated
- 15 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-Myeloablative HLA-Matched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00113828
- Acronym / sponsor ID
- 04-222
- Conditions
- Lymphoma, Leukemia, Multiple Myeloma, Myelodysplastic Syndrome
- Keywords
- Non-Myeloablative, Stem Cell Transplantation, T-cell Depletion, HLA-Matched
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient accrual
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Dana-Farber Cancer Institute
- Study start
- Dec 2004
- Primary completion
- Mar 2007 (actual)
- Study completion
- Mar 2007 (actual)
- First posted
- 13 Jun 2005 (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.
The purpose of this trial is to determine if patients with hematologic diseases who have a HLA 6/6 matched related donor and are not eligible for a standard myeloablative stem cell transplant will have less severe graft versus host disease (GVHD), transplant related mortality, and less graft failure when treated with a non-myeloablative T-cell depleted stem cell transplant.
Detailed description
Our prior experience in the lab and in clinical trials with non-myeloablative HLA-matched and mismatched transplant strategies have been remarkable for a low transplant related mortality rate, but a still formidable risk of GVHD and graft rejection. In this trial, we have incorporated a combination ex-vivo T-cell depletion strategy to prevent GVHD with vigorous in vivo depletion of host (and to a lesser extent donor) T-cells to prevent graft rejection.
Patients will receive non-myeloablative conditioning with cyclophosphamide, thymoglobulin, fludarabine, and thymic irradiation, followed by a T-cell depleted PBSC infusion. Cyclosporine will be given for GVHD prophylaxis, and tapered beginning on day 35. Data from our mouse model and previous clinical trials have demonstrated that this approach can induce mixed chimerism without GVHD, with the potential for conversion of mixed chimerism to full donor hematopoiesis following donor leukocyte infusions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Transplantation | Experimental | Procedure: Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant, Procedure: T-cell depleted peripheral blood stem cell transplantT-cell depleted HLA-matched peripheral blood stem cell transplantation |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Disease statue: NHL, HD, or MM that are chemorefractory or relapsed; CLL that is Rai Stage III/IV, or lymphocyte doubling time of 6 months, or stage I/II that is resistant to > 2 chemotherapy regimens; AML or ALL in 1st or subsequent remission with poor prognostic features; CML in accelerated or blast phae; MDS with life-threatening cytopenias; patients who have had a previous autologous or allogeneic bone marrow or stem cell transplant; other hematologic disorders which allogeneic stem cell transplantation is appropriate where the risk of conventional transplantation is considered to be unacceptably high.
- Estimated disease-free survival of less than one year
- ECOG performance status of 0, 1, or 2
- HLA-genotypically or phenotypically matched (at A, B, DR loci) related donor
Key exclusion criteria (8 listed)
- Patients who life expectancy is limited by diseases other than their hematologic malignancy.
- Cardiac Disease: symptomatic congestive hearth failure, or RVG, or ejection fraction of < 45%, active angina pectoris, or uncontrolled hypertension.
- Pulmonary Disease: severe chronic obstructive lung disease, or symptomatic restrictive lung disease, or DLCO of < 50%.
- Renal Disease: serum creatinine > 2.0 mg/dl or creatinine clearance < 50 ml/min.
- Hepatic Disease: serum bilirubin > 2.0 mg/dl or alkaline phosphatase, SGOT or SGPT > 3 times normal.
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 |
|---|---|---|
| Non-myeloablative Ex-Vivo T-cell Depleted PBSC TransplantAlso: Cyclosporine iv beginning on transplant day -1Rabbit anti-thymocyte globulin 0.5 mg/kg on transplant day-8, 2.5 mg/kg on day-7 and 3.0 mg/kg on day-6; cyclophosphamide 60 mg/kg on days-7,-6; fludarabine 25 mg/m2 on days -5, -4, -3, -2, -1. Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant. | Procedure or surgery | Transplantation |
| T-cell depleted peripheral blood stem cell transplantAlso: Cyclosporine iv beginning on day -1.Rabbit anti-thymocyte globulin 0.5 mg/kg on transplant day-8, 2.5 mg/kg on day-7, 3.0 mg/kg on day-6; cyclophosphamide 60 mg/kg on days -7, -6; fludarabine 25 mg/m2 on days -5 through -1. T-cell depleted peripheral blood stem cell transplant . | Procedure or surgery | Transplantation |
Primary outcome
To evaluate the risks of severe (grade III/IV) GVHD or transplant related mortality at < 100 days following HLA-matched non-myeloablative stem cell transplantation (or following "prophylactic" DLI given for chimerism conversion).
Time frame: 100 days
3 secondary outcomes
To evaluate the incidence of acute and chronic GVHD.
Time frame: indefinite
To evaluate the incidence of graft loss.
Time frame: 100 days
To evaluate progression free and overall survival.
Time frame: indefinite
Results and safety
The study was stopped early (reason given: Insufficient accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2018.
- Individual participant dataSharing planned: No
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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.
Thomas Spitzer, M.D. principal investigator
Massachusetts General Hospital, Harvard University
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 Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant and T-cell depleted peripheral blood stem cell transplant in people with Lymphoma and Leukemia, run by Massachusetts General Hospital 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 4 inclusion and 8 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: stopped early, as of the sponsor's last update on 15 Mar 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 was stopped early (reason given: Insufficient accrual). Results are not available in the source record.
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?
To evaluate the risks of severe (grade III/IV) GVHD or transplant related mortality at < 100 days following HLA-matched non-myeloablative stem cell transplantation (or following "prophylactic" DLI given for chimerism conversion). (time frame: 100 days). 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 15 Mar 2018.