Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissuePhase 1NCT00110071
Iodine I 131 Tositumomab and Fludarabine Phosphate in Treating Older Patients Who Are Undergoing an Autologous or Syngeneic Stem Cell Transplant for Relapsed or Refractory Non-Hodgkin's Lymphoma
A Phase 1 study testing fludarabine phosphate, peripheral blood stem cell transplantation and iodine I 131 tositumomab in people with Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue and Nodal Marginal Zone B-cell Lymphoma, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of fludarabine (fludarabine phosphate) when given together with iodine I 131 tositumomab in treating older patients who are undergoing an autologous or syngeneic stem cell transplant for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Burkitt Lymphoma
- What is being tested?
- fludarabine phosphate, peripheral blood stem cell transplantation and iodine I 131 tositumomab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Jun 2011
- Phase
- Phase 1
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have a histologically confirmed diagnosis of lymphoma expressing the CD20 antigen and generally must have failed at least one prior standard systemic therapy; the exception will be mantle cell lymphoma (MCL) patients, who may be enrolled while in first complete remission (CR) in accordance with current transplant standard of care for these patients
- Creatinine (Cr) < 2.0
- Bilirubin < 1.5 mg/dL, with the exception of patients thought to have Gilbert's syndrome, whom may have a total bilirubin above 1.5 mg/dL
- All patients eligible for therapeutic study must have (>= 2x10^6 CD34/kg) autologous hematopoietic stem cells harvested and cryopreserved, or this number of cells harvested from a syngeneic donor
- Patients must have an expected survival of > 60 days and must be free of major infection
- DONOR: Syngeneic donors must be confirmed syngeneic by ABO typing, human leukocyte antigen (HLA) typing, and variable number tandem repeat (VNTR) analysis
- DONOR: Syngeneic donors must meet eligibility under Standard Practice Guidelines/Standard Treatment
Who cannot join
- Circulating anti-mouse antibody (HAMA) (to be determined before both dosimetry and therapy)
- Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose
- Inability to understand or give an informed consent
- Prior radiation > 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, > 25% of red marrow)
- Central nervous system lymphoma
- Other serious medical conditions considered to represent contraindications to bone marrow transplant (BMT) (e.g., abnormally decreased cardiac ejection fraction, diffusing capacity (DLCO) < 50% predicted, patient on supplemental oxygen, acquired Immunodeficiency syndrome [AIDS], etc.)
Show all 11Show fewer
- Pregnancy
- Prior bone marrow or stem cell transplant
- South West Oncology Group (SWOG) performance status >= 2
- Unable to perform self-care during radiation isolation
- Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma/well differentiated lymphocytic lymphoma
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: A Clinical Trial Evaluating I131-Tositumomab (Anti-CD20) With Escalating Doses of Fludarabine Followed by Autologous or Syngeneic Stem Cell Transplantation for Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma in Patients 60 Years of Age and Older
This phase I trial studies the side effects and best dose of fludarabine (fludarabine phosphate) when given together with iodine I 131 tositumomab in treating older patients who are undergoing an autologous or syngeneic stem cell transplant for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving iodine I 131 tositumomab together with fludarabine followed by autologous stem cell transplant may be an effective treatment for NHL
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the maximally tolerated dose of fludarabine that can be combined with 131I-anti-CD20 (iodine I 131 tositumomab) delivering =< 27Gy to critical normal organs followed by autologous or syngeneic transplantation in patients >= 60 years of age with relapsed B-NHL.
SECONDARY OBJECTIVES:
- To assess the overall and progression-free survival of the above regimen in such patients.
II. To evaluate the response rates of the above therapy.
III. To evaluate the toxicity and tolerability of the above therapy.
IV. To evaluate the feasibility of delivering concurrent high-dose radioimmunotherapy (RIT) and chemotherapy.
OUTLINE: This is a dose-escalation study of fludarabine phosphate as used in combination with I 131 tositumomab and stem cell transplant.
Patients receive a dosimetric dose of iodine I 131 tositumomab intravenously (IV) over 40-60 minutes on day -24 followed by gamma camera imaging over the next 6 days. Patients then receive a therapeutic dose of iodine I 131 tositumomab via central line over 40-60 minutes on day -14. Patients also receive fludarabine phosphate IV once daily (QD) on days -11 to -9 OR days -11 or -7. Patients undergo autologous or syngeneic peripheral blood stem cell transplantation on day 0.
Patients with circulating lymphoma cells by peripheral smear receive tositumomab IV over 1 hour OR rituximab IV over 1 hour followed by tositumomab IV over 1 hour before the dosimetric iodine I 131 tositumomab infusion.
After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months and then annually thereafter.
- Conditions
- Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
- Being tested
- fludarabine phosphate, peripheral blood stem cell transplantation, iodine I 131 tositumomab, laboratory biomarker analysis, flow cytometry
- Medical subject headings
- Lymphoma, B-Cell, Marginal Zone, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Follicular, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called 2-F-ara-AMP, Beneflur, Fludara
Given IV
peripheral blood stem cell transplantationProcedure or surgery
Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Undergo transplantation (infusion of autologous or syngeneic PBSC via central line)
iodine I 131 tositumomabRadiation
Also called 131-I-anti-B1 antibody, 131-I-anti-B1 monoclonal antibody, I131-MOAB-B1, iodine I 131 MOAB anti-B1
Given IV (dosimetric dose) or via central line (therapeutic dose)
laboratory biomarker analysisOther
Correlative studies
flow cytometryOther
Correlative studies
polymerase chain reactionGenetic
Also called PCR
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (chemoradioimmunotherapy) | Experimental | Patients receive a dosimetric dose of iodine I 131 tositumomab IV over 40-60 minutes on day -24 followed by gamma camera imaging over the next 6 days. Patients then receive a therapeutic dose of iodine I 131 tositumomab via central line over 40-60 minutes on day -14. Patients also receive fludarabine phosphate IV QD on days -11 to -9 OR days -11 or -7. Patients undergo autologous or syngeneic peripheral blood stem cell transplantation on day 0. Receives: Drug: fludarabine phosphate; Procedure: peripheral blood stem cell transplantation; Radiation: iodine I 131 tositumomab; Other: laboratory biomarker analysis; Other: flow cytometry; Genetic: polymerase chain reaction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose/dose limiting toxicity
Assessed according to Bearman scale for Regimen-Related Toxicities.
Measured: Up to 30 days post-transplant
Secondary outcomes (4)
Overall and progression-free survival rate
Measured: Up to 6 years
Response rate
Measured: Up to 12 months
Toxicity/tolerability of study regimen
Type, frequency, and severity of adverse events grade 3 and above (assessed by National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v3.0.
Measured: Through day 100 post-transplant
Feasibility of concurrent high-dose radioimmunotherapy and chemotherapy
Ability to administer complete course of I 131-tositumomab and fludarabine phosphate as descried in protocol.
Measured: Through day -7 prior to transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2005 (estimated)
- Study startJan 2005
- Primary completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ajay Gopal, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00110071
- Sponsor's protocol ID
- 1943.00
- Other IDs
- NCI-2009-01470, P01CA044991
- Status last verified
- Aug 2014
- First submitted
- 3 May 2005
- Last updated
- 6 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Gopal AK, Gooley TA, Rajendran JG, Pagel JM, Fisher DR, Maloney DG, Appelbaum FR, Cassaday RD, Shields A, Press OW. Myeloablative I-131-tositumomab with escalating doses of fludarabine and autologous hematopoietic transplantation for adults age >/= 60 years with B cell lymphoma. Biol Blood Marrow Transplant. 2014 Jun;20(6):770-5. doi: 10.1016/j.bbmt.2014.02.004. Epub 2014 Feb 12.
PubMed 24530971
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial Evaluating I131-Tositumomab (Anti-CD20) With Escalating Doses of Fludarabine Followed by Autologous or Syngeneic Stem Cell Transplantation for Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma in Patients 60 Years of Age and Older
- ClinicalTrials.gov ID
- NCT00110071
- Acronym / sponsor ID
- 1943.00
- Conditions
- Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jan 2005
- Primary completion
- Jun 2011 (actual)
- First posted
- 4 May 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.
This phase I trial studies the side effects and best dose of fludarabine (fludarabine phosphate) when given together with iodine I 131 tositumomab in treating older patients who are undergoing an autologous or syngeneic stem cell transplant for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving iodine I 131 tositumomab together with fludarabine followed by autologous stem cell transplant may be an effective treatment for NHL
Detailed description
PRIMARY OBJECTIVES:
- To estimate the maximally tolerated dose of fludarabine that can be combined with 131I-anti-CD20 (iodine I 131 tositumomab) delivering =< 27Gy to critical normal organs followed by autologous or syngeneic transplantation in patients >= 60 years of age with relapsed B-NHL.
SECONDARY OBJECTIVES:
- To assess the overall and progression-free survival of the above regimen in such patients.
II. To evaluate the response rates of the above therapy.
III. To evaluate the toxicity and tolerability of the above therapy.
IV. To evaluate the feasibility of delivering concurrent high-dose radioimmunotherapy (RIT) and chemotherapy.
OUTLINE: This is a dose-escalation study of fludarabine phosphate as used in combination with I 131 tositumomab and stem cell transplant.
Patients receive a dosimetric dose of iodine I 131 tositumomab intravenously (IV) over 40-60 minutes on day -24 followed by gamma camera imaging over the next 6 days. Patients then receive a therapeutic dose of iodine I 131 tositumomab via central line over 40-60 minutes on day -14. Patients also receive fludarabine phosphate IV once daily (QD) on days -11 to -9 OR days -11 or -7. Patients undergo autologous or syngeneic peripheral blood stem cell transplantation on day 0.
Patients with circulating lymphoma cells by peripheral smear receive tositumomab IV over 1 hour OR rituximab IV over 1 hour followed by tositumomab IV over 1 hour before the dosimetric iodine I 131 tositumomab infusion.
After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months and then annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (chemoradioimmunotherapy) | Experimental | Drug: fludarabine phosphate, Procedure: peripheral blood stem cell transplantation, Radiation: iodine I 131 tositumomab, Other: laboratory biomarker analysis, Other: flow cytometry, Genetic: polymerase chain reactionPatients receive a dosimetric dose of iodine I 131 tositumomab IV over 40-60 minutes on day -24 followed by gamma camera imaging over the next 6 days. Patients then receive a therapeutic dose of iodine I 131 tositumomab via central line over 40-60 minutes on day -14. Patients also receive fludarabine phosphate IV QD on days -11 to -9 OR days -11 or -7. Patients undergo autologous or syngeneic peripheral blood stem cell transplantation on day 0. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must have a histologically confirmed diagnosis of lymphoma expressing the CD20 antigen and generally must have failed at least one prior standard systemic therapy; the exception will be mantle cell lymphoma (MCL) patients, who may be enrolled while in first complete remission (CR) in accordance with current transplant standard of care for these patients
- Creatinine (Cr) < 2.0
- Bilirubin < 1.5 mg/dL, with the exception of patients thought to have Gilbert's syndrome, whom may have a total bilirubin above 1.5 mg/dL
- All patients eligible for therapeutic study must have (>= 2x10^6 CD34/kg) autologous hematopoietic stem cells harvested and cryopreserved, or this number of cells harvested from a syngeneic donor
- Patients must have an expected survival of > 60 days and must be free of major infection
Key exclusion criteria (11 listed)
- Circulating anti-mouse antibody (HAMA) (to be determined before both dosimetry and therapy)
- Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose
- Inability to understand or give an informed consent
- Prior radiation > 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, > 25% of red marrow)
- Central nervous system lymphoma
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 |
|---|---|---|
| fludarabine phosphateAlso: 2-F-ara-AMP, Beneflur, FludaraGiven IV | Drug | Treatment (chemoradioimmunotherapy) |
| peripheral blood stem cell transplantationAlso: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cellUndergo transplantation (infusion of autologous or syngeneic PBSC via central line) | Procedure or surgery | Treatment (chemoradioimmunotherapy) |
| iodine I 131 tositumomabAlso: 131-I-anti-B1 antibody, 131-I-anti-B1 monoclonal antibody, I131-MOAB-B1, iodine I 131 MOAB anti-B1Given IV (dosimetric dose) or via central line (therapeutic dose) | Radiation | Treatment (chemoradioimmunotherapy) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (chemoradioimmunotherapy) |
| flow cytometryCorrelative studies | Other | Treatment (chemoradioimmunotherapy) |
| polymerase chain reactionAlso: PCRCorrelative studies | Genetic | Treatment (chemoradioimmunotherapy) |
Primary outcome
Maximum tolerated dose/dose limiting toxicity
Time frame: Up to 30 days post-transplant
Assessed according to Bearman scale for Regimen-Related Toxicities.
4 secondary outcomes
Overall and progression-free survival rate
Time frame: Up to 6 years
Response rate
Time frame: Up to 12 months
Toxicity/tolerability of study regimen
Time frame: Through day 100 post-transplant
Feasibility of concurrent high-dose radioimmunotherapy and chemotherapy
Time frame: Through day -7 prior to transplant
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 6 Aug 2014.
- Derived from this study: PubMed 24530971Gopal AK, Gooley TA, Rajendran JG, Pagel JM, Fisher DR, Maloney DG, Appelbaum FR, Cassaday RD, Shields A, Press OW. Myeloablative I-131-tositumomab with escalating doses of fludarabine and autologous hematopoietic transplantation for adults age >/= 60 years with B cell lymphoma. Biol Blood Marrow Transplant. 2014 Jun;20(6):770-5. doi: 10.1016/j.bbmt.2014.02.004. Epub 2014 Feb 12.
Related trials for Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
RecruitingPhase 2
Non-covalent BTK Inhibitor Nemtabrutinib in Combination With the CD20 Monoclonal Antibody Rituximab for the Treatment of Marginal Zone Lymphoma
Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma, Gastric Mucosa-Associated Lymphoid Tissue Lymphoma
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia
Active, not recruitingPhase 1/2
Selinexor Plus Combination Chemotherapy in Treating Patients With Advanced B Cell Non-Hodgkin Lymphoma
Diffuse Large B-Cell Lymphoma, Recurrent B-Cell Non-Hodgkin Lymphoma
Active, not recruitingObservational study
Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
Hematopoietic/Lymphoid Cancer, Accelerated Phase Chronic Myelogenous Leukemia
RecruitingPhase 2
Epcoritamab in Patients With Newly Diagnosed Marginal Zone Lymphoma (MZL)
Marginal Zone Lymphoma, Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
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.
Ajay Gopal principal investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing fludarabine phosphate, peripheral blood stem cell transplantation and iodine I 131 tositumomab in people with Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue and Nodal Marginal Zone B-cell Lymphoma, run by Fred Hutchinson 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 11 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 6 Aug 2014. 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 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.
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 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?
Maximum tolerated dose/dose limiting toxicity (time frame: Up to 30 days post-transplant). 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 NCT00110071, 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 6 Aug 2014.