Non-Hodgkin's LymphomaPhase 2NCT01408563
Reduced Intensity Double Umbilical Cord Blood Transplantation
A Phase 2 study testing Fludarabine, Melphalan and Total Body Radiation in people with Non-Hodgkin's Lymphoma and Hodgkin's Lymphoma, run by Massachusetts General Hospital at 3 sites in United States.
Trial summary
This trial will use two cord blood units for transplantation using a reduced intensity regimen rather than using intense doses of chemotherapy and radiation therapy. Two cord blood units (double cord blood) are being used, as the numbers of blood cells in one unit are too few to allow successful growth of these cells. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma
- What is being tested?
- Fludarabine, Melphalan and Total Body Radiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 3 sitesUnited States
- Study dates
- Dec 2011to Jun 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hematologic malignancy for whom allogeneic stem cell transplantation is deemed clinically appropriate
- Appropriate candidate for reduced intensity regimen, according to the treating physician
- Lack of 6/6/ or 5/6 HLA-matched related, 8/8/ HLA-matched unrelated donor, or unrelated donor not available with a time frame necessary to perform a potentially curative stem cell transplant
- Able to comply with the requirements for care after allogeneic stem cell transplantation
Who cannot join
- Cardiac disease: symptomatic congestive heart failure or evidence of left ventricular dysfunction
- Pulmonary disease: symptomatic chronic obstructive lung disease, symptomatic restrictive lung disease
- Renal disease
- Hepatic disease
- Neurologic disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation
- HIV-positive
- Uncontrolled infection
- Pregnant or breast-feeding
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: A Phase II Study of Reduced Intensity Double Umbilical Cord Blood Transplantation Using Fludarabine, Melphalan, and Low Dose Total Body Radiation
This trial will use two cord blood units for transplantation using a reduced intensity regimen rather than using intense doses of chemotherapy and radiation therapy. Two cord blood units (double cord blood) are being used, as the numbers of blood cells in one unit are too few to allow successful growth of these cells.
Because the risk of infection, particularly virus infection, is high after double cord blood transplant, this study seeks to reduce the rise of virus infection by using a reduced intensity regimen without a medicine called antithymocyte globulin (ATG), as used in prior cord blood transplants. Subjects will receive two chemotherapy drugs, melphalan and fludarabine, and low dose of total body radiation (one treatment) instead of the ATG. The number of patients with virus infections in this study will be compared to our prior experience using the ATG.
Read the detailed description
Subjects will receive their transplants as in-patients.
- IV-Catheter
- one or two IV catheters will be placed on the day of hospital admission
- Conditioning
- Fludarabine IV six days before transplant (days -7, -6, -5. -4, -3, -2)
- Melphalan IV (day -1)
- Total body radiation on day 0 (same day as transplant)
- Immunosuppressive Therapy
- Tacrolimus and sirolimus beginning day -3, daily for 6-9 months post-transplant. Given IV as in-patient, orally as out-patient
- Infusion of Cord Blood units
- 2 cord blood units IV on Day 0 Routine post-transplant supportive care will be provided
- Conditions
- Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Chronic Lymphocytic Leukemia, Acute Myelogenous Leukemia
- Being tested
- Fludarabine, Melphalan, Total Body Radiation, Cord Blood
- Keywords
- NHL, lymphoma, leukemia, myelodysplastic disorder, aplastic anemia
- Medical subject headings
- Lymphoma, Non-Hodgkin, Hodgkin Disease, Multiple Myeloma, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myeloid, Acute, Lymphoma, Leukemia, Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Also called Fludara
30 mg/m2/day IV x 6 days
MelphalanDrug
100 mg/m2/day IV x 1 day
Total Body RadiationRadiation
200 cGy on Day 0
Cord BloodBiological
2 cord blood units IV
| Study group | Role | What they receive |
|---|---|---|
| Fludarabine/Melphalan/TBI | Experimental | All patients receive same therapy Receives: Drug: Fludarabine; Drug: Melphalan; Radiation: Total Body Radiation; Biological: Cord Blood |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Clinically Significant Infection
The one year significant infection rate (infections requiring medical intervention) after double umbilical cord blood transplant using a novel conditioning regimen of fludarabine/melphalan/low dose total body radiation. The data is shown as the number of significant infections participants experienced during the first year, measured from the start of treatment.
Measured: 1 Year
Secondary outcomes (12)
Median Time to Neutrophil Engraftment
The median number of days measured from the time of transplantation, until the first documented neutrophil engraftment. neutrophil engraftment is defined as the first of 3 consecutive days of absolute neutrophil count > 500 neutrophils per microliter of blood.
Measured: From the time of transplantation, until the time of neutrophil engraftment, median duration of 24 days
Median Time to Platelet Engraftment
The time to platelet engraftment is measured from the time of transplantation until the time of first documented platelet engraftment. Platelet engraftment is defined as a platelet count ≥ 20,000/µL for three consecutive measurements over three or more days. The first of the three days will be designated the day of platelet engraftment. Subjects must not have had platelet transfusions during the preceding 3 days or in the following 7 days after the day of engraftment, unless the platelet transfusion is being given specifically to achieve a platelet threshold to allow an elective invasive procedure, such as a central catheter removal.
Measured: From the time of transplantation, until the time of platelet engraftment, median duration of 52 days
Number of Participants With Primary Graft Failure
Primary graft failure is defined as the failure to achieve an absolute neutrophil count (ANC) >500/ µL by day 42, in the absence of relapse.
Measured: From the time of transplantation until 42 days post transplantation
Rates of Grade II-IV and Grade III-IV Acute Graft Versus Host Disease (GVHD) at 100 Days
Acute GVHD is assessed using Consensus Criteria:
Organ Classifications:
- 0: No rash due to GVHD; Bilirubin < 2 mg/dL; < 500 mL diarrhea/ day
- 1: Maculopapular rash < 25% of body surface; Bilirubin 2-3 mg/dL; 500 to 999 mL diarrhea/ day or persistent nausea with histologic evidence of GVHD in stomach/ duodenum
- 2: Maculopapular rash 25-50% of body surface; Bilirubin 3.1-6 mg/dL; 1,000 to 1,499 mL diarrhea/ day
- 3: Maculopapular rash > 50% of body surface; Bilirubin 6.1-15 mg/dL; 1,500 or more mL diarrhea/ day
- 4: Generalized erythroderma with bullous formation; Bilirubin > 15 mg/dL; Severe abdominal pain with or without ileus
Overall Clinical Grade:
- 0: No Stage 1-4 of any organ
- I: Stage 1-2 rash and no liver or gut involvement
- II: Stage 3 rash, or Stage 1 liver involvement, or Stage 1 gut involvement
- III: None to Stage 3 skin rash with Stage 2-3 liver involvement, or Stage 2-4 gut involvement
- IV: Stage 4 skin rash, or Stage 4 liver involvement
Measured: 100 Days
The Rate of Chronic GVHD
Chronic Graft Versus Host Disease (GVHD) is assessed using the National Institutes of Health (NIH) consensus criteria.
Measured: From the time of transplantation until the time of chronic GVHD onset, up to 1 year
100-day Treatment Related Mortality
The percentage of treatment related participant deaths within 100 days of receiving umbilical cord blood transplantation. All deaths in the absence of relapse of the primary malignancy will be considered treatment related mortality.
Measured: 100 Days
Immune Reconstitution - Median CD4 Count at 12 Months
Measured: 1 Year
Relapse-free Survival
The percentage of participants that have not died or had disease progression by two years. Relapse is defined by either morphological or cytogenetic evidence of the original malignancy consistent with pre-transplant features.
Measured: 2 years
Overall Survival
The percentage of participants alive at two years
Measured: 2 years
1 Year Relapse Rate
The percentage of participants that relapsed within 12 months. Relapse is defined by either morphological or cytogenetic evidence of the original malignancy consistent with pre-transplant features.
Measured: 1 year
Rate of Post-transplant Lymphoma
The number of participants that were found to have lymphoma post-transplant.
Measured: 2.5 years
Median Thrombopoietin Levels After Transplant
Measured: 30 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2011 (estimated)
- Study startDec 2011
- Primary completionJun 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Hodgkin's 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
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zachariah Michael DeFilipp, Massachusetts General Hospital
- Investigators
- Zachariah DeFilipp, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01408563
- Sponsor's protocol ID
- 11-085
- Status last verified
- Dec 2018
- First submitted
- 2 Aug 2011
- Last updated
- 23 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Reduced Intensity Double Umbilical Cord Blood Transplantation Using Fludarabine, Melphalan, and Low Dose Total Body Radiation
- ClinicalTrials.gov ID
- NCT01408563
- Acronym / sponsor ID
- 11-085
- Conditions
- Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Chronic Lymphocytic Leukemia, Acute Myelogenous Leukemia
- Keywords
- NHL, lymphoma, leukemia, myelodysplastic disorder, aplastic anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Dec 2011
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 3 Aug 2011 (estimated)
- Results
- Posted 21 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial will use two cord blood units for transplantation using a reduced intensity regimen rather than using intense doses of chemotherapy and radiation therapy. Two cord blood units (double cord blood) are being used, as the numbers of blood cells in one unit are too few to allow successful growth of these cells.
Because the risk of infection, particularly virus infection, is high after double cord blood transplant, this study seeks to reduce the rise of virus infection by using a reduced intensity regimen without a medicine called antithymocyte globulin (ATG), as used in prior cord blood transplants. Subjects will receive two chemotherapy drugs, melphalan and fludarabine, and low dose of total body radiation (one treatment) instead of the ATG. The number of patients with virus infections in this study will be compared to our prior experience using the ATG.
Detailed description
Subjects will receive their transplants as in-patients.
- IV-Catheter
- one or two IV catheters will be placed on the day of hospital admission
- Conditioning
- Fludarabine IV six days before transplant (days -7, -6, -5. -4, -3, -2)
- Melphalan IV (day -1)
- Total body radiation on day 0 (same day as transplant)
- Immunosuppressive Therapy
- Tacrolimus and sirolimus beginning day -3, daily for 6-9 months post-transplant. Given IV as in-patient, orally as out-patient
- Infusion of Cord Blood units
- 2 cord blood units IV on Day 0 Routine post-transplant supportive care will be provided
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fludarabine/Melphalan/TBI | Experimental | Drug: Fludarabine, Drug: Melphalan, Radiation: Total Body Radiation, Biological: Cord BloodAll patients receive same therapy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Hematologic malignancy for whom allogeneic stem cell transplantation is deemed clinically appropriate
- Appropriate candidate for reduced intensity regimen, according to the treating physician
- Lack of 6/6/ or 5/6 HLA-matched related, 8/8/ HLA-matched unrelated donor, or unrelated donor not available with a time frame necessary to perform a potentially curative stem cell transplant
- Able to comply with the requirements for care after allogeneic stem cell transplantation
Key exclusion criteria (8 listed)
- Cardiac disease: symptomatic congestive heart failure or evidence of left ventricular dysfunction
- Pulmonary disease: symptomatic chronic obstructive lung disease, symptomatic restrictive lung disease
- Renal disease
- Hepatic disease
- Neurologic disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation
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 |
|---|---|---|
| FludarabineAlso: Fludara30 mg/m2/day IV x 6 days | Drug | Fludarabine/Melphalan/TBI |
| Melphalan100 mg/m2/day IV x 1 day | Drug | Fludarabine/Melphalan/TBI |
| Total Body Radiation200 cGy on Day 0 | Radiation | Fludarabine/Melphalan/TBI |
| Cord Blood2 cord blood units IV | Biological | Fludarabine/Melphalan/TBI |
Primary outcome
Number of Participants With a Clinically Significant Infection
Time frame: 1 Year
The one year significant infection rate (infections requiring medical intervention) after double umbilical cord blood transplant using a novel conditioning regimen of fludarabine/melphalan/low dose total body radiation. The data is shown as the number of significant infections participants experienced during the first year, measured from the start of treatment.
12 secondary outcomes
Median Time to Neutrophil Engraftment
Time frame: From the time of transplantation, until the time of neutrophil engraftment, median duration of 24 days
Median Time to Platelet Engraftment
Time frame: From the time of transplantation, until the time of platelet engraftment, median duration of 52 days
Number of Participants With Primary Graft Failure
Time frame: From the time of transplantation until 42 days post transplantation
Rates of Grade II-IV and Grade III-IV Acute Graft Versus Host Disease (GVHD) at 100 Days
Time frame: 100 Days
The Rate of Chronic GVHD
Time frame: From the time of transplantation until the time of chronic GVHD onset, up to 1 year
100-day Treatment Related Mortality
Time frame: 100 Days
Immune Reconstitution - Median CD4 Count at 12 Months
Time frame: 1 Year
Relapse-free Survival
Time frame: 2 years
Overall Survival
Time frame: 2 years
1 Year Relapse Rate
Time frame: 1 year
Rate of Post-transplant Lymphoma
Time frame: 2.5 years
Median Thrombopoietin Levels After Transplant
Time frame: 30 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Zachariah DeFilipp, MD principal investigator
Massachusetts General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fludarabine, Melphalan and Total Body Radiation in people with Non-Hodgkin's Lymphoma and Hodgkin's Lymphoma, run by Massachusetts General Hospital at 3 sites 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: finished, as of the sponsor's last update on 23 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Yes. Results are posted in the registry (first posted 21 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With a Clinically Significant Infection (time frame: 1 Year). 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 23 Jan 2019; AzTrials last refreshed its copy on 6 Nov 2026.