Non-Hodgkin's LymphomaPhase 1/2NCT00802113
Autologous and Allogeneic Transplant for Relapsed Lymphoma
A Phase 1/2 study testing Fludarabine, Busulfan and Anti-Thymocyte Globulin in people with Non-Hodgkin's Lymphoma and Hodgkins Disease, run by Columbia University at 6 sites in United States.
Trial summary
The sequential combination of myeloablative therapy and autologous stem cell transplantation (APBSCT) followed by a reduced intensity allogeneic stem cell transplant (Allo SCT) and post SCT adoptive cellular immunotherapy will be well tolerated in patients with refractory or recurrent non-Hodgkin's lymphoma (NHL) and… Read more about this study
- Who is it for?
- Ages Up to 55 years
- Conditions the study is for
- Non-Hodgkin's Lymphoma, Hodgkins Disease
- What is being tested?
- Fludarabine, Busulfan and Anti-Thymocyte Globulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 6 sitesUnited States
- Study dates
- Jun 2003to 22 Oct 2014
- 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 Up to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient must have adequate organ function as below
- Adequate renal function defined as:
- Serum creatinine less than or equal to 2.0 x normal, or
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 40 ml/min/m2 or >60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
- Adequate liver function defined as:
- Total bilirubin <2.0 x normal; or
Show all 27Show fewer
- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase (AST)) or serum glutamic-pyruvic transaminase (SPGT) (alanine aminotransferase (ALT)) <5.0 x normal
- Adequate cardiac function defined as:
- Shortening fraction of >27% by echocardiogram, or
- Ejection fraction of >47% by radionuclide angiogram or echocardiogram
- Adequate pulmonary function defined as:
- Diffusing capacity of the lungs for carbon monoxide (DLCO) >50% by pulmonary function test for autologous transplant
- DLCO > 40% by pulmonary function test for reduced intensity allogeneic transplant
- For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% in room air.
- Disease Status (Eligibility)
- Patients with Non-Hodgkin's Lymphoma with either of the following:
- Primary induction failure (failure to achieve initial CR) who have a partial response (PR) or stable disease (SD) with reinduction chemotherapy. *All patients are required to have a biopsy regardless of positron emission tomography (PET)/Gallium results.
- Patients with 1st PR, 2nd CR, 2nd PR, or 2nd SD following reinduction chemotherapy
- Patients with 3rd CR, 3rd PR, 3rd SD following reinduction chemotherapy
- Patients with Hodgkin's Disease with either of the following:
- Primary induction failure (failure to achieve initial CR) and/or primary refractory disease.
- First relapse
- Early relapse (within 12 months off therapy) (excluding those who received no therapy or radiation therapy only for initial therapy)
- Late relapse (greater than 12 months off therapy). Only patients with recurrent Stage III or IV disease and/or those with B symptoms at relapse (all other late relapses are excluded).
- Second relapse.
- Third relapse.
- Patients must achieve a CR, PR or SD after reinduction chemotherapy.
Who cannot join
- Patients with NHL or HD with 4th or greater CR, PR, and/or SD
- Patients with progressive disease (PD) unresponsive to reinduction chemo, radio, or immunotherapy
- Hodgkin's Disease in late relapse (other than those discussed above).
- Patients with post-transplant lymphoproliferative disease following a solid organ transplantation or AIDS associated NHL
- Patients who don't have an eligible donor
- Women who are pregnant
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Children's Memorial Hospital in Chicago
Chicago, Illinois, 60611
Duke University
Durham, North Carolina, 27708
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Columbia University Medical Center
New York, New York, 10032
New York Medical College
Valhalla, New York, 10595
About this study
Official title: Sequential Myeloablative Stem Cell Transplantation and Reduced Intensity Allogeneic Stem Cell Transplantation in Patients With Refractory or Recurrent Non-Hodgkin's Lymphoma and Hodgkin's Disease
The sequential combination of myeloablative therapy and autologous stem cell transplantation (APBSCT) followed by a reduced intensity allogeneic stem cell transplant (Allo SCT) and post SCT adoptive cellular immunotherapy will be well tolerated in patients with refractory or recurrent non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD).
Read the detailed description
Lymphomas are the third most common group of cancers in children and adolescents in the United States. While Hodgkin's Disease (HD) has been described for many years, some subtypes of the non-Hodgkin's Lymphomas (NHL) have only recently been described. Non-Hodgkin's lymphomas traditionally have been classified as low, intermediate or high grade based on their clinical aggressiveness. More recently they have been divided into two major subgroups indolent and aggressive lymphomas by the current National Cancer Institute (NCI/PDQ) reference. Among children, aggressive histologies are prevalent including small non-cleaved cell lymphoma, lymphoblastic lymphoma, and diffuse large cell lymphoma. The most common histologic classifications of childhood non-Hodgkin's lymphoma over the past 30 years has included the morphological schema developed by Rappaport, the morphologically and immunologically based schema of Lukes and Collins, the Kiel classifications, the prognostic sub-groupings of the National Cancer Institute's Working Formulation, and the most recently developed classification that utilizes morphological, immunophenotypic and genetic information in the Revised European-American Lymphoma (REAL) classification.
- Conditions
- Non-Hodgkin's Lymphoma, Hodgkins Disease
- Being tested
- Fludarabine, Busulfan, Anti-Thymocyte Globulin
- Keywords
- Autologous Stem Cell Transplant, Cord Blood Transplant, Allogeneic Stem Cell Transplant, Relapsed Lymphoma
- Medical subject headings
- Lymphoma, Non-Hodgkin, Hodgkin Disease, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Also called Fludara
Fludarabine 30 mg/m2 x 5 days
BusulfanDrug
Also called Busulfex
Busulfan 3.2 mg/kg/day x 2 days
Anti-Thymocyte GlobulinDrug
Also called ATG
Anti-Thymocyte Globulin 2.0 mg/kg/day x 4 days
| Study group | Role | What they receive |
|---|---|---|
| Arm A - Family Donor | Experimental | Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. The non-ablative therapy will be busulfan and fludarabine, Usually large (myeloablative) doses of these drugs are used for an allogeneic transplant. However, in this study lower doses (non-ablative) of chemotherapy will be given. In patients who still have evidence of disease after allogeneic transplant, additional donor immune cells (donor lymphocyte infusion) (DLI) will be given twice to further treat the lymphoma. Receives: Drug: Fludarabine; Drug: Busulfan |
| Arm B - Unrelated Cord Blood or Adult | Experimental | Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world. If a closely matched cord blood donor or unrelated adult donor is found, non-ablative chemotherapy with busulfan, fludarabine and antithymocyte globulin (ATG) followed by the infusion of matched unrelated cord blood cells or adult donor stem cells or bone marrow to restore the bone marrow will be given. Receives: Drug: Fludarabine; Drug: Busulfan; Drug: Anti-Thymocyte Globulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of Subjects With a Complete Response (CR) Following Myeloablative Conditioning (MAC) and Autologous Stem Cell Transplantation (AutoSCT)
Complete Response is defined as the complete resolution of B symptoms (i.e., weight loss, night sweats and fever) and normalization of all sites of disease on the basis of physical exam, bone marrow biopsy, and imaging studies.
Measured: Up to 1 year post-transplantation
Total Number of Subjects With a Disease Relapse or Progression Following MAC AutoSCT
Includes subjects with any measurable growth of disease in a previously affected site or detection of disease in a new site confirmed by biopsy.
Measured: Up to 1 year post-transplantation
Total Number of Subjects With Partial Response or Stable Disease Following MAC AutoSCT
Total includes subjects with partial response and patients with stable disease, defined as <50% reduction in measurable disease or the uninterrupted persistence of B symptoms.
Measured: Up to 1 year post-transplantation
Secondary outcomes (4)
Time to Neutrophil Engraftment
Following MAC AutoSCT, the median time to neutrophil (PMN) recovery will be measured.
Measured: Up to 1 year post-transplantation
Time to Platelet Engraftment
Following MAC AutoSCT, the median time to platelet recovery will be measured.
Measured: Up to 1 year post-transplantation
Total Number of Subjects With Grade II-IV Acute Graft-versus-Host-Disease (GVHD)
The criteria for grading is based on extent of organ involvement (i.e., Skin, Liver and Gut - rash on >50% of skin, bilirubin 2-3 mg/dl, diarrhea > 500 ml/day) with Grade II being better outcome and Grade IV being worse outcome.
Measured: Up to 1 year post-transplantation
Total Number of Subjects That Experienced Transplant-related Mortality (TRM)
Status as subjects died post-AlloHCT
Measured: Up to 1 year post-transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2008 (estimated)
- Study startJun 2003
- Primary completionOct 2014
- Study completion22 Oct 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 Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prakash Satwani, Columbia University
- Investigators
- Prakash Satwani, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00802113
- Sponsor's protocol ID
- AAAA5185
- Other IDs
- CHNY-01-501
- Status last verified
- Mar 2019
- First submitted
- 5 May 2008
- Last updated
- 27 Mar 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 27 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sequential Myeloablative Stem Cell Transplantation and Reduced Intensity Allogeneic Stem Cell Transplantation in Patients With Refractory or Recurrent Non-Hodgkin's Lymphoma and Hodgkin's Disease
- ClinicalTrials.gov ID
- NCT00802113
- Acronym / sponsor ID
- AAAA5185
- Conditions
- Non-Hodgkin's Lymphoma, Hodgkins Disease
- Keywords
- Autologous Stem Cell Transplant, Cord Blood Transplant, Allogeneic Stem Cell Transplant, Relapsed Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- Jun 2003
- Primary completion
- Oct 2014 (actual)
- Study completion
- 22 Oct 2014 (actual)
- First posted
- 4 Dec 2008 (estimated)
- Results
- Posted 27 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The sequential combination of myeloablative therapy and autologous stem cell transplantation (APBSCT) followed by a reduced intensity allogeneic stem cell transplant (Allo SCT) and post SCT adoptive cellular immunotherapy will be well tolerated in patients with refractory or recurrent non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD).
Detailed description
Lymphomas are the third most common group of cancers in children and adolescents in the United States. While Hodgkin's Disease (HD) has been described for many years, some subtypes of the non-Hodgkin's Lymphomas (NHL) have only recently been described. Non-Hodgkin's lymphomas traditionally have been classified as low, intermediate or high grade based on their clinical aggressiveness. More recently they have been divided into two major subgroups indolent and aggressive lymphomas by the current National Cancer Institute (NCI/PDQ) reference. Among children, aggressive histologies are prevalent including small non-cleaved cell lymphoma, lymphoblastic lymphoma, and diffuse large cell lymphoma. The most common histologic classifications of childhood non-Hodgkin's lymphoma over the past 30 years has included the morphological schema developed by Rappaport, the morphologically and immunologically based schema of Lukes and Collins, the Kiel classifications, the prognostic sub-groupings of the National Cancer Institute's Working Formulation, and the most recently developed classification that utilizes morphological, immunophenotypic and genetic information in the Revised European-American Lymphoma (REAL) classification.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A - Family Donor | Experimental | Drug: Fludarabine, Drug: BusulfanFludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. The non-ablative therapy will be busulfan and fludarabine, Usually large (myeloablative) doses of these drugs are used for an allogeneic transplant. However, in this study lower doses (non-ablative) of chemotherapy will be given. In patients who still have evidence of disease after allogeneic transplant, additional donor immune cells (donor lymphocyte infusion) (DLI) will be given twice to further treat the lymphoma. |
| Arm B - Unrelated Cord Blood or Adult | Experimental | Drug: Fludarabine, Drug: Busulfan, Drug: Anti-Thymocyte GlobulinFludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world. If a closely matched cord blood donor or unrelated adult donor is found, non-ablative chemotherapy with busulfan, fludarabine and antithymocyte globulin (ATG) followed by the infusion of matched unrelated cord blood cells or adult donor stem cells or bone marrow to restore the bone marrow will be given. |
Who may qualify
- Ages
- Up to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (27 listed)
- Patient must have adequate organ function as below
- Adequate renal function defined as:
- Adequate liver function defined as:
- Adequate cardiac function defined as:
- Adequate pulmonary function defined as:
Key exclusion criteria (6 listed)
- Patients with NHL or HD with 4th or greater CR, PR, and/or SD
- Patients with progressive disease (PD) unresponsive to reinduction chemo, radio, or immunotherapy
- Hodgkin's Disease in late relapse (other than those discussed above).
- Patients with post-transplant lymphoproliferative disease following a solid organ transplantation or AIDS associated NHL
- Patients who don't have an eligible donor
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: FludaraFludarabine 30 mg/m2 x 5 days | Drug | Arm A - Family Donor, Arm B - Unrelated Cord Blood or Adult |
| BusulfanAlso: BusulfexBusulfan 3.2 mg/kg/day x 2 days | Drug | Arm A - Family Donor, Arm B - Unrelated Cord Blood or Adult |
| Anti-Thymocyte GlobulinAlso: ATGAnti-Thymocyte Globulin 2.0 mg/kg/day x 4 days | Drug | Arm B - Unrelated Cord Blood or Adult |
Primary outcome
Total Number of Subjects With a Complete Response (CR) Following Myeloablative Conditioning (MAC) and Autologous Stem Cell Transplantation (AutoSCT)
Time frame: Up to 1 year post-transplantation
Complete Response is defined as the complete resolution of B symptoms (i.e., weight loss, night sweats and fever) and normalization of all sites of disease on the basis of physical exam, bone marrow biopsy, and imaging studies.
Total Number of Subjects With a Disease Relapse or Progression Following MAC AutoSCT
Time frame: Up to 1 year post-transplantation
Includes subjects with any measurable growth of disease in a previously affected site or detection of disease in a new site confirmed by biopsy.
Total Number of Subjects With Partial Response or Stable Disease Following MAC AutoSCT
Time frame: Up to 1 year post-transplantation
Total includes subjects with partial response and patients with stable disease, defined as <50% reduction in measurable disease or the uninterrupted persistence of B symptoms.
4 secondary outcomes
Time to Neutrophil Engraftment
Time frame: Up to 1 year post-transplantation
Time to Platelet Engraftment
Time frame: Up to 1 year post-transplantation
Total Number of Subjects With Grade II-IV Acute Graft-versus-Host-Disease (GVHD)
Time frame: Up to 1 year post-transplantation
Total Number of Subjects That Experienced Transplant-related Mortality (TRM)
Time frame: Up to 1 year post-transplantation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 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.
Prakash Satwani, MD principal investigator
Columbia University
6 sites 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 Fludarabine, Busulfan and Anti-Thymocyte Globulin in people with Non-Hodgkin's Lymphoma and Hodgkins Disease, run by Columbia University at 6 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 27 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 27 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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 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 27 Mar 2019). 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?
Total Number of Subjects With a Complete Response (CR) Following Myeloablative Conditioning (MAC) and Autologous Stem Cell Transplantation (AutoSCT) (time frame: Up to 1 year post-transplantation). The study lists 3 primary outcomes in all. 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 27 Mar 2019.