LeukemiaPhase 2NCT00387959
Chemotherapy, Radiation Therapy, Rituximab, and Umbilical Cord Blood Transplant in Treating Patients With B-Cell Non-Hodgkin's Lymphoma
A Phase 2 study testing filgrastim, rituximab and cyclophosphamide in people with Leukemia and Lymphoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, total-body irradiation, and rituximab before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- What is being tested?
- filgrastim, rituximab and cyclophosphamide
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2006to Apr 2014
- 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
DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following:
- CD20+* aggressive B-cell non-Hodgkin's lymphoma (NHL), including 1 of the following:
- Diffuse large cell (DLC) NHL meeting 1 of the following criteria:
- Relapsed disease after initial therapy but failed to mobilize or had bone marrow involvement and therefore is not suitable for an autologous stem cell transplantation
- High-intermediate or high-risk, second-line, age-adjusted International Prognostic Index (IPI) score and in second complete remission (CR) or partial remission (PR) after prior autologous stem cell transplantation
- Failed prior autologous stem cell transplantation and in at least PR after salvage chemotherapy
- Large cell transformation of indolent NHL/chronic lymphocytic leukemia (CLL) meeting the following criteria:
- CR/PR of the large cell component of disease after salvage chemotherapy or autologous stem cell transplantation
- Mantle cell lymphoma meeting 1 of the following criteria:
- High-risk, as defined by p53 positivity and in first CR/PR after initial therapy
- Relapsed disease after initial therapy and in second or third CR/PR after salvage chemotherapy
- CD20+* indolent NHL or CLL meeting the following criteria:
- Must be in second or subsequent progression (pre-allograft cytoreduction necessary but CR/PR not required)
- Indolent NHL includes, but is not limited to, any of the following:
- Follicular NHL
- Small cell NHL
- Marginal zone NHL NOTE: *CD20 positivity must be demonstrated within the past 12 months
- Relapsed disease must be biopsy proven
- Prior pre-allograft cytoreduction may have included 1 of the following:
- Single autologous stem cell transplantation with high-dose chemotherapy conditioning, if appropriate, and no conditioning prior to transplantation
- Two or more courses of intensive combination chemotherapy (e.g., rituximab, irinotecan hydrochloride, cetuximab, epirubicin hydrochloride [RICE]) as appropriate according to diagnosis and prior therapy
- Heavily pre-treated CLL patients in whom further combination chemotherapy is not appropriate may receive single-agent intermediate-dose cyclophosphamide for 2-3 courses
- No mantle cell or DLC NHL with progressive disease at allograft work-up
- No suitable matched related or unrelated donor available
- Two umbilical cord blood (UCB) units available meeting the following criteria:
- Units and recipient must be ≥ 4/6 HLA-A and -B antigen and DRB1 allele matched
- Each unit must have ≥ 1.5 x 10^7 total nucleated cells/recipient body weight
PATIENT CHARACTERISTICS:
- Karnofsky performance score 70-100%
- Creatinine clearance ≥ 50 mL/min
- Bilirubin < 2.5 mg/dL
- AST and ALT ≤ 3 times upper limit of normal (unless due to benign congenital hyperbilirubinemia)
- Spirometry and corrected DLCO ≥ 50% normal
- LVEF ≥ 40%
- Albumin ≥ 2.5 g/dL
- No active and uncontrolled infection at time of transplantation, including active infection with Aspergillus or other mold
- No HIV positivity
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No more than 120 days since prior autologous stem cell transplantation
- No more than 60 days since prior chemotherapy
- No prior allogeneic transplantation
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Non-Myeloablative Conditioning Regimen With Peri-Transplant Rituximab and the Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With B Cell Lymphoid Malignancies
RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, total-body irradiation, and rituximab before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving chemotherapy and radiation therapy together with rituximab and an umbilical cord blood transplant works in treating patients with B-cell non-Hodgkin's lymphoma.
Read the detailed description
OBJECTIVES:
Primary
- Determine the overall and event-free survival at 1 year in patients with B-cell lymphoid malignancies treated with a nonmyeloablative conditioning regimen, rituximab, and umbilical cord blood (UCB) transplantation (UCBT).
Secondary
- Determine the speed of neutrophil and platelet recovery post allograft in these patients.
- Determine the incidence and speed of donor-derived engraftment and contribution of each UCB unit to engraftment in these patients.
- Determine the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days in these patients.
- Determine the incidence and severity of chronic GVHD at 1 year in these patients.
- Determine the incidence of serious infectious complications and correlate with laboratory measurements of immune recovery in these patients.
- Determine the response to vaccination after UCBT in these patients.
- Determine the incidence of treatment-related mortality at 100 days and 180 days in these patients.
- Determine the incidence of malignant relapse or disease progression at 1 and 2 years in these patients.
- Determine the probabilities of overall and event-free survival at 2 years after UCBT in these patients.
- Determine the performance of laboratory studies investigating double-unit biology and correlate with unit engraftment in these patients.
OUTLINE:
- Pre-transplant rituximab therapy: Patients receive rituximab IV on days -8 or -7 and on day -4.
- Nonmyeloablative conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV on day -6. Patients also undergo total-body irradiation on day -1.
- Umbilical cord blood transplantation: Patients undergo umbilical cord blood transplantation on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 7 and continuing until blood counts recover.
- Post-transplant rituximab therapy: Patients receive rituximab IV on days 7, 14, 21, and 28.
- Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2-4 hours or orally twice daily on days -3 to 100, followed by a taper. Patients also receive mycophenolate mofetil IV or orally three times daily on days -3 to 45, followed by a taper.
Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
- Being tested
- filgrastim, rituximab, cyclophosphamide, cyclosporine, fludarabine phosphate
- Keywords
- recurrent mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, B-cell chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent marginal zone lymphoma, recurrent adult diffuse small cleaved cell lymphoma, splenic marginal zone lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma
- Medical subject headings
- Leukemia, Lymphoma, Lymphoma, Mantle-Cell, Lymphoma, Large B-Cell, Diffuse, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Non-Hodgkin, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
rituximabBiological
cyclophosphamideDrug
cyclosporineDrug
allogeneic hematopoietic stem cell transplantationProcedure or surgery
umbilical cord blood transplantationProcedure or surgery
total-body irradiationRadiation
| Study group | Role | What they receive |
|---|---|---|
| Unrelated Donor Umbilical Cord Transplant | Experimental | Non-Myeloablative Conditioning Regimen with Peri-Transplant Rituximab and the Transplantation of Unrelated Donor Umbilixal Cord Blood Receives: Biological: filgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: mycophenolate mofetil; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: umbilical cord blood transplantation; Radiation: total-body irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival at 1 Year After Transplantation
The number of patients survival status 1 year after transplantation
Measured: 1 Year after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2006 (estimated)
- Study startJul 2006
- Primary completionApr 2014
- Study completionApr 2014
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 LeukemiaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Juliet Barker, MBBS, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00387959
- Sponsor's protocol ID
- 06-066
- Other IDs
- MSKCC-06066
- Status last verified
- Dec 2015
- First submitted
- 12 Oct 2006
- Last updated
- 1 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-Myeloablative Conditioning Regimen With Peri-Transplant Rituximab and the Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With B Cell Lymphoid Malignancies
- ClinicalTrials.gov ID
- NCT00387959
- Acronym / sponsor ID
- 06-066
- Keywords
- recurrent mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, B-cell chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jul 2006
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 13 Oct 2006 (estimated)
- Results
- Posted 1 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, total-body irradiation, and rituximab before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving chemotherapy and radiation therapy together with rituximab and an umbilical cord blood transplant works in treating patients with B-cell non-Hodgkin's lymphoma.
Detailed description
OBJECTIVES:
Primary
- Determine the overall and event-free survival at 1 year in patients with B-cell lymphoid malignancies treated with a nonmyeloablative conditioning regimen, rituximab, and umbilical cord blood (UCB) transplantation (UCBT).
Secondary
- Determine the speed of neutrophil and platelet recovery post allograft in these patients.
- Determine the incidence and speed of donor-derived engraftment and contribution of each UCB unit to engraftment in these patients.
- Determine the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days in these patients.
- Determine the incidence and severity of chronic GVHD at 1 year in these patients.
- Determine the incidence of serious infectious complications and correlate with laboratory measurements of immune recovery in these patients.
- Determine the response to vaccination after UCBT in these patients.
- Determine the incidence of treatment-related mortality at 100 days and 180 days in these patients.
- Determine the incidence of malignant relapse or disease progression at 1 and 2 years in these patients.
- Determine the probabilities of overall and event-free survival at 2 years after UCBT in these patients.
- Determine the performance of laboratory studies investigating double-unit biology and correlate with unit engraftment in these patients.
OUTLINE:
- Pre-transplant rituximab therapy: Patients receive rituximab IV on days -8 or -7 and on day -4.
- Nonmyeloablative conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV on day -6. Patients also undergo total-body irradiation on day -1.
- Umbilical cord blood transplantation: Patients undergo umbilical cord blood transplantation on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 7 and continuing until blood counts recover.
- Post-transplant rituximab therapy: Patients receive rituximab IV on days 7, 14, 21, and 28.
- Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2-4 hours or orally twice daily on days -3 to 100, followed by a taper. Patients also receive mycophenolate mofetil IV or orally three times daily on days -3 to 45, followed by a taper.
Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Unrelated Donor Umbilical Cord Transplant | Experimental | Biological: filgrastim, Biological: rituximab, Drug: cyclophosphamide, Drug: cyclosporine, Drug: fludarabine phosphate, Drug: mycophenolate mofetil, Procedure: allogeneic hematopoietic stem cell transplantation, Procedure: umbilical cord blood transplantation, Radiation: total-body irradiationNon-Myeloablative Conditioning Regimen with Peri-Transplant Rituximab and the Transplantation of Unrelated Donor Umbilixal Cord Blood |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| filgrastim | Biological | Unrelated Donor Umbilical Cord Transplant |
| rituximab | Biological | Unrelated Donor Umbilical Cord Transplant |
| cyclophosphamide | Drug | Unrelated Donor Umbilical Cord Transplant |
| cyclosporine | Drug | Unrelated Donor Umbilical Cord Transplant |
| fludarabine phosphate | Drug | Unrelated Donor Umbilical Cord Transplant |
| mycophenolate mofetil | Drug | Unrelated Donor Umbilical Cord Transplant |
| allogeneic hematopoietic stem cell transplantation | Procedure or surgery | Unrelated Donor Umbilical Cord Transplant |
| umbilical cord blood transplantation | Procedure or surgery | Unrelated Donor Umbilical Cord Transplant |
| total-body irradiation | Radiation | Unrelated Donor Umbilical Cord Transplant |
Primary outcome
Survival at 1 Year After Transplantation
Time frame: 1 Year after transplant
The number of patients survival status 1 year after transplantation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2016.
- 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.
Juliet Barker, MBBS principal investigator
Memorial Sloan Kettering Cancer Center
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 filgrastim, rituximab and cyclophosphamide in people with Leukemia and Lymphoma, run by Memorial Sloan Kettering Cancer Center 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?
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 1 Feb 2016. 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?
Yes. Results are posted in the registry (first posted 1 Feb 2016). 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?
Survival at 1 Year After Transplantation (time frame: 1 Year after transplant). 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 1 Feb 2016.