LymphomaPhase 1/2NCT00048737
Safety and Efficacy of 90Y Zevalin in Nonmyeloablative Transplantation for Lymphoid Malignancies
A Phase 1/2 study testing Zevalin Radioimmunotherapy, Rituximab and Fludarabine in people with Lymphoma and Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to see if low intensity chemotherapy given together with the new drug 90Y Zevalin, followed by a transplant of blood or marrow stem cells from a donor can increase the length of remission in patients with leukemia and lymphoma. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- What is being tested?
- Zevalin Radioimmunotherapy, Rituximab and Fludarabine
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2002to Dec 2011
- Phase
- Phase 1/2
- 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
- Patients in relapse or considered at high risk for relapse or refractory CD-20-positive B-cell NHL or CLL. Patients considered for high risk of relapse are patients who do not achieve complete response (CR) with frontline chemotherapy, CLL is Richter's and CLL with high risk chromosomal abnormalities.
- Measurable disease.
- Age 18-70 years, expected survival >/= 3 months, performance status 0 to 2.
- Availability of a matched related donor.
- </+ 50% bone marrow involvement.
- CLL with </+ 10,000 circulating lymphocytes.
- Availability of a matched related or unrelated donor.
Who cannot join
- Prior myeloablative therapies or radioimmunotherapy.
- Prior external beam radiation therapy to >25% of active bone marrow.
- Prior therapy with 90Y Zevalin or Campath.
- CNS lymphoma, HIV, HTLV-1 positivity, some creatinine >1.6 mg/dl or serum bilirubin >1.5 mg/dl.
- Pregnancy or lactation.
- Symptomatic pulmonary or cardiac disease.
Trial locations and contacts
1 site in 1 country.
About this study
The goal of this clinical research study is to see if low intensity chemotherapy given together with the new drug 90Y Zevalin, followed by a transplant of blood or marrow stem cells from a donor can increase the length of remission in patients with leukemia and lymphoma. The safety of this treatment will also be studied.
Read the detailed description
Rituxan is an antibody made from human and mouse protein. It reacts with a certain antigen on lymphoma cells and causes the body's immune system to destroy the lymphoma cells. 90Y Zevalin and 111In Zevalin are murine-based antibodies combined with a radioactive agent that can also destroy lymphoma cells. Unlike Rituxan, 90Y Zevalin cannot be traced by regular scanning and requires indium to determine its distribution through the body.
Before treatment starts, patients will have a physical exam, including blood tests and urine tests. Women who are able to have children must have a negative blood pregnancy test. Bone marrow samples will be taken. For bone marrow sampling, a large needle is placed in the hipbone after it has been numbed. The bone marrow is then withdrawn through the needle. Patients will have a chest x-ray, computed tomography (CT) scans, an EKG, and tests of lung function.
Blood tests, urine tests, bone marrow sampling, and x-rays will be done as needed to track the effects of the transplant. Patients will have transfusions of blood and platelets as needed. Blood tests will be done daily while patients are in the hospital.
Patients in this study will receive an unlabeled antibody form of Y2B8 called rituxan by vein followed by a dose of 111In Zevalin by vein. 111In Zevalin includes the radioactive agent indium, which shows up when patients have x-rays or scans. The scans can show where and how fast the drug travels in the body and how long the drug stays in the body. Doctors need to be able to see how much of the drug goes to the tumor and how much goes to normal organs to see if it is safe to give 90Y Zevalin on an outpatient basis. A scan will be taken 48 to 72 hours after 111In Zevalin is given.
If the radiation in the 111In Zevalin is not a threat to normal organs and bone marrow, patients may receive 90Y Zevalin. Seven days after the 111In Zevalin injection, patients will receive a second dose of rituxan followed by a dose of 90Y Zevalin.
Patients will also receive fludarabine and cyclophosphamide daily for 3 days. All of the chemotherapy drugs will be given through a catheter (plastic tube) that extends into the large chest vein. The catheter will be left in place throughout treatment. When chemotherapy is finished, blood stem cells from a donor will be given through the catheter. Granulocyte colony-stimulating factor (G-CSF or GCSF), a hormone that helps the production of blood cells, will be injected under the skin once a day until the neutrophil counts recover in the blood. Patients will receive methotrexate for 3 days post transplant and tacrolimus for 6 months or more to prevent graft versus host disease.
All patients will have complete checkups, including blood and urine tests 2 or 3 times during the first 12 weeks of the study. Tumors will be measured by CT or MRI and gallium scans. Patients will be asked to fill out a survey about quality of life issues (maintaining normal routine, family life, social life, pain). It takes about half an hour to fill out the survey. A bone marrow sample may be taken. A test of heart function will be done. Checkups and tests will be done every 3 months for 1 year and then every 6 months for 4 more years.
Treatment will be given in the hospital at M. D. Anderson. Patients will need to stay in the hospital for about 3 to 4 weeks. Patients must stay in the Houston area for about 100 days after the transplant. After that, patients will need to return to Houston from time to time for blood tests, urine tests, and other exams.
This is an investigational study. 90Y-Zevalin is approved by the FDA for relapsed and refractory lymphoma. Its use in this trial, however, is investigational. About 70 patients will take part in this study. All will be enrolled at M. D. Anderson.
- Being tested
- Zevalin Radioimmunotherapy, Rituximab, Fludarabine, Cyclophosphamide, Allogeneic Stem Cell Transplantation
- Keywords
- Leukemia, Lymphoma, Lymphoid Malignancy, Cyclophosphamide, Cytoxan, Neosar, Fludarabine, Fludarabine Phosphate, Fludara, Rituximab, Rituxan, Zevalin, Indium Zevalin, 90Y Zevalin, CD-20-positive, B-cell Lymphoma, CD-20-positive B-cell Lymphoma, NHL, CLL, Chronic Lymphocytic Leukemia
- Medical subject headings
- Lymphoma, Leukemia, Lymphoma, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zevalin RadioimmunotherapyDrug
Also called 90Y Zevalin
Escalating single dose of 90Y Zevalin 0.2-0.3-0.4 mCi/kg
RituximabDrug
Also called Rituxan
250 mg/m^2 on day 1 and day 8
FludarabineDrug
Also called Fludarabine phosphate, Fludara
30 mg/m^2/day for 3 days
CyclophosphamideDrug
Also called Cytoxan, Neosar
750 mg/m^2/day for 3 days, given on the same days as fludarabine, at 4-hour intervals
Allogeneic Stem Cell TransplantationProcedure or surgery
Also called ASCT
Allogeneic stem cell transplantation 2 days after chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| 90Y Zevalin in ASCT | Experimental | Allogeneic Stem Cell (AST) Transplantation with 90Y Zevalin/Cyclophosphamide/Fludarabine as a preparative regimen. Receives: Drug: Zevalin Radioimmunotherapy; Drug: Rituximab; Drug: Fludarabine; Drug: Cyclophosphamide; Procedure: Allogeneic Stem Cell Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Graft Failure
Graft failure is defined as either lack of hematologic recovery or lack of or loss of detectable donor cells.
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2002 (estimated)
- Study startOct 2002
- Primary completionDec 2011
- Study completionDec 2011
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Biogen
- Responsible party
- Sponsor
- Investigators
- Issa F. Khouri, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00048737
- Sponsor's protocol ID
- ID01-233
- Status last verified
- Jun 2013
- First submitted
- 6 Nov 2002
- Last updated
- 13 Jun 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. doi: 10.1182/blood-2012-03-417808. Epub 2012 May 14.
PubMed 22586182
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of 90Y Zevalin in Nonmyeloablative Transplantation for Lymphoid Malignancies
- ClinicalTrials.gov ID
- NCT00048737
- Acronym / sponsor ID
- ID01-233
- Keywords
- Leukemia, Lymphoma, Lymphoid Malignancy, Cyclophosphamide, Cytoxan, Neosar, Fludarabine, Fludarabine Phosphate
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Biogen
- Study start
- Oct 2002
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 8 Nov 2002 (estimated)
- Results
- Posted 13 Jun 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to see if low intensity chemotherapy given together with the new drug 90Y Zevalin, followed by a transplant of blood or marrow stem cells from a donor can increase the length of remission in patients with leukemia and lymphoma. The safety of this treatment will also be studied.
Detailed description
Rituxan is an antibody made from human and mouse protein. It reacts with a certain antigen on lymphoma cells and causes the body's immune system to destroy the lymphoma cells. 90Y Zevalin and 111In Zevalin are murine-based antibodies combined with a radioactive agent that can also destroy lymphoma cells. Unlike Rituxan, 90Y Zevalin cannot be traced by regular scanning and requires indium to determine its distribution through the body.
Before treatment starts, patients will have a physical exam, including blood tests and urine tests. Women who are able to have children must have a negative blood pregnancy test. Bone marrow samples will be taken. For bone marrow sampling, a large needle is placed in the hipbone after it has been numbed. The bone marrow is then withdrawn through the needle. Patients will have a chest x-ray, computed tomography (CT) scans, an EKG, and tests of lung function.
Blood tests, urine tests, bone marrow sampling, and x-rays will be done as needed to track the effects of the transplant. Patients will have transfusions of blood and platelets as needed. Blood tests will be done daily while patients are in the hospital.
Patients in this study will receive an unlabeled antibody form of Y2B8 called rituxan by vein followed by a dose of 111In Zevalin by vein. 111In Zevalin includes the radioactive agent indium, which shows up when patients have x-rays or scans. The scans can show where and how fast the drug travels in the body and how long the drug stays in the body. Doctors need to be able to see how much of the drug goes to the tumor and how much goes to normal organs to see if it is safe to give 90Y Zevalin on an outpatient basis. A scan will be taken 48 to 72 hours after 111In Zevalin is given.
If the radiation in the 111In Zevalin is not a threat to normal organs and bone marrow, patients may receive 90Y Zevalin. Seven days after the 111In Zevalin injection, patients will receive a second dose of rituxan followed by a dose of 90Y Zevalin.
Patients will also receive fludarabine and cyclophosphamide daily for 3 days. All of the chemotherapy drugs will be given through a catheter (plastic tube) that extends into the large chest vein. The catheter will be left in place throughout treatment. When chemotherapy is finished, blood stem cells from a donor will be given through the catheter. Granulocyte colony-stimulating factor (G-CSF or GCSF), a hormone that helps the production of blood cells, will be injected under the skin once a day until the neutrophil counts recover in the blood. Patients will receive methotrexate for 3 days post transplant and tacrolimus for 6 months or more to prevent graft versus host disease.
All patients will have complete checkups, including blood and urine tests 2 or 3 times during the first 12 weeks of the study. Tumors will be measured by CT or MRI and gallium scans. Patients will be asked to fill out a survey about quality of life issues (maintaining normal routine, family life, social life, pain). It takes about half an hour to fill out the survey. A bone marrow sample may be taken. A test of heart function will be done. Checkups and tests will be done every 3 months for 1 year and then every 6 months for 4 more years.
Treatment will be given in the hospital at M. D. Anderson. Patients will need to stay in the hospital for about 3 to 4 weeks. Patients must stay in the Houston area for about 100 days after the transplant. After that, patients will need to return to Houston from time to time for blood tests, urine tests, and other exams.
This is an investigational study. 90Y-Zevalin is approved by the FDA for relapsed and refractory lymphoma. Its use in this trial, however, is investigational. About 70 patients will take part in this study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 90Y Zevalin in ASCT | Experimental | Drug: Zevalin Radioimmunotherapy, Drug: Rituximab, Drug: Fludarabine, Drug: Cyclophosphamide, Procedure: Allogeneic Stem Cell TransplantationAllogeneic Stem Cell (AST) Transplantation with 90Y Zevalin/Cyclophosphamide/Fludarabine as a preparative regimen. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients in relapse or considered at high risk for relapse or refractory CD-20-positive B-cell NHL or CLL. Patients considered for high risk of relapse are patients who do not achieve complete response (CR) with frontline chemotherapy, CLL is Richter's and CLL with high risk chromosomal abnormalities.
- Measurable disease.
- Age 18-70 years, expected survival >/= 3 months, performance status 0 to 2.
- Availability of a matched related donor.
- </+ 50% bone marrow involvement.
Key exclusion criteria (6 listed)
- Prior myeloablative therapies or radioimmunotherapy.
- Prior external beam radiation therapy to >25% of active bone marrow.
- Prior therapy with 90Y Zevalin or Campath.
- CNS lymphoma, HIV, HTLV-1 positivity, some creatinine >1.6 mg/dl or serum bilirubin >1.5 mg/dl.
- Pregnancy or lactation.
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 |
|---|---|---|
| Zevalin RadioimmunotherapyAlso: 90Y ZevalinEscalating single dose of 90Y Zevalin 0.2-0.3-0.4 mCi/kg | Drug | 90Y Zevalin in ASCT |
| RituximabAlso: Rituxan250 mg/m^2 on day 1 and day 8 | Drug | 90Y Zevalin in ASCT |
| FludarabineAlso: Fludarabine phosphate, Fludara30 mg/m^2/day for 3 days | Drug | 90Y Zevalin in ASCT |
| CyclophosphamideAlso: Cytoxan, Neosar750 mg/m^2/day for 3 days, given on the same days as fludarabine, at 4-hour intervals | Drug | 90Y Zevalin in ASCT |
| Allogeneic Stem Cell TransplantationAlso: ASCTAllogeneic stem cell transplantation 2 days after chemotherapy | Procedure or surgery | 90Y Zevalin in ASCT |
Primary outcome
Number of Participants With Graft Failure
Time frame: 100 days
Graft failure is defined as either lack of hematologic recovery or lack of or loss of detectable donor cells.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22586182Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. doi: 10.1182/blood-2012-03-417808. Epub 2012 May 14.
- The University of Texas M.D.Anderson Cancer Center official websiteLink provided by the sponsor.
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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.
Issa F. Khouri, MD principal investigator
M.D. Anderson 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 1/2 study testing Zevalin Radioimmunotherapy, Rituximab and Fludarabine in people with Lymphoma and Leukemia, run by M.D. Anderson 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?
The sponsor lists 7 inclusion and 6 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 Jun 2013. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 13 Jun 2013). 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 Graft Failure (time frame: 100 days). 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 NCT00048737, which also lists 1 linked publication.
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 Jun 2013.