LeukemiaPhase 2NCT00006252
Fludarabine and Cyclophosphamide Followed by Peripheral Stem Cell Transplant in Treating Patients With Leukemia or Lymphoma
A Phase 2 study testing fludarabine phosphate, Cyclophosphamide and PBSC in people with Leukemia and Lymphoma, run by Cancer and Leukemia Group B at 19 sites in United States.
Trial summary
RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study
- Who is it for?
- Ages Up to 69 years
- What is being tested?
- fludarabine phosphate, Cyclophosphamide and PBSC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 19 sitesUnited States
- Study dates
- Feb 2001to Oct 2011
- Phase
- Phase 2
- 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 Up to 69 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- One of the following histologically confirmed diagnoses:
- Chronic lymphocytic leukemia
- Absolute lymphocytosis greater than 5,000/mm^3
- Morphologically mature lymphocytes with less than 55% prolymphocytes
- Lymphocyte phenotypic expression of CD19 and CD5
- Failed at least 1 prior regimen
- Progressive lymphocytosis with more than 50% increase in peripheral lymphocytosis or a progressive lymph node or spleen enlargement (at least 25% enlargement or the appearance of new lymph nodes) that persists for at least 4 weeks despite concurrent or prior drug treatment OR
- At least 1 of the following high-risk factors and not in first complete remission
= 17p deletion = 11q deletion
- Unmutated VH gene status
- p53 mutations
- Prolymphocytic leukemia (PLL)
- Absolute lymphocytosis greater than 5,000/mm^3
- Morphologically mature lymphocytes with more than 55% prolymphocytes
- Low-grade non-Hodgkin's lymphoma
- Small lymphocytic lymphoma
- Follicular center lymphoma (grade I or II)
- Diffuse (predominately small cell type)
- Marginal zone, B-cell lymphoma
- No transformed lymphoma
- Failure of at least 1 prior regimen OR
- At least 3 of the following risk factors:
- Over 60 years of age
- Performance status greater than 1
- LDH greater than normal
- More than 1 site of extranodal disease
- Disease stage III or IV
- Mantle cell lymphoma
- Any stage
- Ineligible for protocol CALGB-59908
- At least 1 prior treatment regimen
- At least 1 of the following:
- Immunophenotypic expression of CD5 and CD19 and absence of CD23
- Cytogenetic analysis with presence of t(11;14)
- Overexpression of cyclin D1
- Rearrangement of BCL1 gene
- Responsive or stable disease to most recent prior therapy
- Prior therapy for PLL not required
- Must have HLA identical sibling (6/6) donor by serologic typing (A, B, DR)
- No syngeneic donors
- No age restriction NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
Age:
- Under 70
Performance status:
- Not specified
Life expectancy:
- Not specified
Hematopoietic:
- Granulocyte count at least 500/mm^3*
- Platelet count at least 50,000/mm^3* NOTE: *Unless attributable to disease
Hepatic:
- Bilirubin no greater than 3 times upper limit of normal (ULN)*
- AST no greater than 3 times ULN* NOTE: *Unless attributable to disease
Renal:
- Creatinine clearance at least 40 mL/min, unless attributable to disease
Cardiovascular:
- LVEF at least 30% by MUGA
Pulmonary:
- DLCO greater than 40%
- No symptomatic pulmonary disease
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No uncontrolled diabetes mellitus
- No active serious infection
- No known hypersensitivity to E. coli-derived products
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No prior autologous transplantation
Chemotherapy:
- At least 4 weeks since prior chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- At least 4 weeks since prior radiotherapy
Surgery:
- At least 4 weeks since prior surgery
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263-0001
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599-7295
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
Columbus, Ohio, 43210-1240
Union Hospital Cancer Center at Union Hospital
Elkton MD, Maryland, 21921
Elmhurst Hospital Center
Elmhurst, New York, 11373
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, 52242
Queens Cancer Center of Queens Hospital
Jamaica, New York, 11432
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, 92093-0658
Beebe Medical Center
Lewes, Delaware, 19958
Mount Sinai Medical Center
New York, New York, 10029
CCOP - Christiana Care Health Services
Newark, Delaware, 19713
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224-1791
Massey Cancer Center at Virginia Commonwealth University
Richmond, Virginia, 23298-0037
Veterans Affairs Medical Center - San Diego
San Diego, California, 92161
UCSF Comprehensive Cancer Center
San Francisco, California, 94115
Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees
Voorhees Township, New Jersey, 08043
St. Francis Hospital
Wilmington, Delaware, 19805
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157-1096
UMASS Memorial Cancer Center - University Campus
Worcester, Massachusetts, 01655
About this study
Official title: Minimal Ablation and Cellular Immune Therapy of Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Low-Grade Non-Hodgkin's Lymphoma, and Mantle Cell Lymphoma With Allogeneic Donor Stem Cells
RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
PURPOSE: This phase II trial is studying how well fludarabine and cyclophosphamide followed by peripheral stem cell transplant works in treating patients with leukemia or lymphoma.
Read the detailed description
OBJECTIVES:
- Determine the feasibility of fludarabine and cyclophosphamide followed by allogeneic peripheral blood stem cell transplantation, in terms of 6-month treatment-related mortality, in patients with chronic lymphocytic leukemia, prolymphocytic leukemia, low-grade non-Hodgkin's lymphoma, or mantle cell lymphoma.
- Determine the 6-month and 12-month probabilities of response in patients treated with this regimen.
- Determine the time to disease progression in patients responding to this regimen.
- Determine the percentage of donor chimerism achieved in patients treated with this regimen.
- Determine the risk of acute and chronic graft-versus-host disease in patients treated with this regimen.
- Determine the toxic effects of this regimen in these patients.
- Determine the overall survival and disease-free survival of patients treated with this regimen.
OUTLINE: This is a multicenter study.
Patients receive fludarabine IV over 30 minutes on days -7 to -3 and cyclophosphamide IV over 1 to 2 hours on days -5 to -3. Patients undergo allogeneic peripheral blood stem cell transplantation on days 0-1. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 5 and continuing until blood counts recover.
Patients with no signs of active graft-versus host disease and stable or progressive disease receive donor lymphocytes IV over 2 hours beginning after day 120. Patients may receive a total of 3 infusions at least 8 weeks apart if disease remains stable or progressive.
Patients are followed every 3 months for 2 years and then every 6 months for 5 years.
PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study.
- Being tested
- fludarabine phosphate, Cyclophosphamide, PBSC, G-CSF, Donor lymphocytes
- Keywords
- refractory chronic lymphocytic leukemia, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage I adult diffuse small cleaved cell lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV adult diffuse small cleaved cell lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, prolymphocytic leukemia, stage I mantle cell lymphoma, contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, contiguous stage II adult diffuse small cleaved cell lymphoma, contiguous stage II mantle cell lymphoma, noncontiguous stage II grade 1 follicular lymphoma
- Medical subject headings
- Leukemia, Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Follicular, Lymphoma, Non-Hodgkin, Leukemia, Prolymphocytic, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
30 mg/sq m/day IV infusion for 5 days (Days -7 thru -3)
CyclophosphamideDrug
1 g/sq m/day IV infusion x 3 days (Days -5 thru -3)
PBSCBiological
2-8,000,000/kg CD34+ cells via infusion on Day 0
G-CSFDrug
5 ug/kg/day subQ injection until ANC > 1000/uL for 3 days beginning Day 5
Donor lymphocytesBiological
10,000,000 CD3+ cells/kg via infusion
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic Stem Cell Tx | Experimental | minimal ablation and cellular immune therapy with allogeneic donor stem cell therapy Receives: Drug: fludarabine phosphate; Drug: Cyclophosphamide; Biological: PBSC; Drug: G-CSF; Biological: Donor lymphocytes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-related mortality within the first 6 months post-transplant
Measured: 6 months post chemo initiation
Secondary outcomes (3)
Response
Measured: 6 months & 12 months
Percentage of patients achieving complete donor chimerism or mixed donor chimerism
Measured: 90 days post transplant
Survival
Disease free and overall survival will be assessed
Measured: 5 years post study entry
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startFeb 2001
- Primary completionJan 2007
- Study completionOct 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 LeukemiaStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cancer and Leukemia Group B
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Thomas Shea, MD, Study chair, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006252
- Sponsor's protocol ID
- CALGB-109901
- Other IDs
- U10CA031946, CALGB-109901, CDR0000068185
- Status last verified
- Jul 2016
- First submitted
- 11 Sep 2000
- Last updated
- 18 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Shea T, Johnson J, Westervelt P, Farag S, McCarty J, Bashey A, Isola L, Baxter-Lowe LA, Kelly M, Owzar K, Linker C; Cancer and Leukemia Group B. Reduced-intensity allogeneic transplantation provides high event-free and overall survival in patients with advanced indolent B cell malignancies: CALGB 109901. Biol Blood Marrow Transplant. 2011 Sep;17(9):1395-403. doi: 10.1016/j.bbmt.2011.01.016. Epub 2011 Feb 3.
PubMed 21296675
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Minimal Ablation and Cellular Immune Therapy of Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Low-Grade Non-Hodgkin's Lymphoma, and Mantle Cell Lymphoma With Allogeneic Donor Stem Cells
- ClinicalTrials.gov ID
- NCT00006252
- Acronym / sponsor ID
- CALGB-109901
- Keywords
- refractory chronic lymphocytic leukemia, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage I adult diffuse small cleaved cell lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage IV grade 1 follicular lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Cancer and Leukemia Group BResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2001
- Primary completion
- Jan 2007 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 27 Jan 2003 (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.
RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
PURPOSE: This phase II trial is studying how well fludarabine and cyclophosphamide followed by peripheral stem cell transplant works in treating patients with leukemia or lymphoma.
Detailed description
OBJECTIVES:
- Determine the feasibility of fludarabine and cyclophosphamide followed by allogeneic peripheral blood stem cell transplantation, in terms of 6-month treatment-related mortality, in patients with chronic lymphocytic leukemia, prolymphocytic leukemia, low-grade non-Hodgkin's lymphoma, or mantle cell lymphoma.
- Determine the 6-month and 12-month probabilities of response in patients treated with this regimen.
- Determine the time to disease progression in patients responding to this regimen.
- Determine the percentage of donor chimerism achieved in patients treated with this regimen.
- Determine the risk of acute and chronic graft-versus-host disease in patients treated with this regimen.
- Determine the toxic effects of this regimen in these patients.
- Determine the overall survival and disease-free survival of patients treated with this regimen.
OUTLINE: This is a multicenter study.
Patients receive fludarabine IV over 30 minutes on days -7 to -3 and cyclophosphamide IV over 1 to 2 hours on days -5 to -3. Patients undergo allogeneic peripheral blood stem cell transplantation on days 0-1. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 5 and continuing until blood counts recover.
Patients with no signs of active graft-versus host disease and stable or progressive disease receive donor lymphocytes IV over 2 hours beginning after day 120. Patients may receive a total of 3 infusions at least 8 weeks apart if disease remains stable or progressive.
Patients are followed every 3 months for 2 years and then every 6 months for 5 years.
PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogeneic Stem Cell Tx | Experimental | Drug: fludarabine phosphate, Drug: Cyclophosphamide, Biological: PBSC, Drug: G-CSF, Biological: Donor lymphocytesminimal ablation and cellular immune therapy with allogeneic donor stem cell therapy |
Who may qualify
- Ages
- Up to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, 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 |
|---|---|---|
| fludarabine phosphate30 mg/sq m/day IV infusion for 5 days (Days -7 thru -3) | Drug | Allogeneic Stem Cell Tx |
| Cyclophosphamide1 g/sq m/day IV infusion x 3 days (Days -5 thru -3) | Drug | Allogeneic Stem Cell Tx |
| PBSC2-8,000,000/kg CD34+ cells via infusion on Day 0 | Biological | Allogeneic Stem Cell Tx |
| G-CSF5 ug/kg/day subQ injection until ANC > 1000/uL for 3 days beginning Day 5 | Drug | Allogeneic Stem Cell Tx |
| Donor lymphocytes10,000,000 CD3+ cells/kg via infusion | Biological | Allogeneic Stem Cell Tx |
Primary outcome
Treatment-related mortality within the first 6 months post-transplant
Time frame: 6 months post chemo initiation
3 secondary outcomes
Response
Time frame: 6 months & 12 months
Percentage of patients achieving complete donor chimerism or mixed donor chimerism
Time frame: 90 days post transplant
Survival
Time frame: 5 years post study entry
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 18 Jul 2016.
- Results publication: PubMed 21296675Shea T, Johnson J, Westervelt P, Farag S, McCarty J, Bashey A, Isola L, Baxter-Lowe LA, Kelly M, Owzar K, Linker C; Cancer and Leukemia Group B. Reduced-intensity allogeneic transplantation provides high event-free and overall survival in patients with advanced indolent B cell malignancies: CALGB 109901. Biol Blood Marrow Transplant. 2011 Sep;17(9):1395-403. doi: 10.1016/j.bbmt.2011.01.016. Epub 2011 Feb 3.
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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.
Thomas Shea, MD study chair
UNC Lineberger Comprehensive Cancer Center
19 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 phosphate, Cyclophosphamide and PBSC in people with Leukemia and Lymphoma, run by Cancer and Leukemia Group B at 19 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?
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 18 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 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?
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?
Treatment-related mortality within the first 6 months post-transplant (time frame: 6 months post chemo initiation). 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 NCT00006252, 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 18 Jul 2016.