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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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
Conditions the study is for
Leukemia, Lymphoma
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

Other trials in United States

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.

Conditions
Leukemia, Lymphoma
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.

  • fludarabine phosphateDrug

    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 groups in NCT00006252
Study groupRoleWhat they receive
Allogeneic Stem Cell TxExperimentalminimal 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.

  1. Treatment-related mortality within the first 6 months post-transplant

    Measured: 6 months post chemo initiation

Secondary outcomes (3)
  1. Response

    Measured: 6 months & 12 months

  2. Percentage of patients achieving complete donor chimerism or mixed donor chimerism

    Measured: 90 days post transplant

  3. 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.

  1. First posted27 Jan 2003 (estimated)
  2. Study startFeb 2001
  3. Primary completionJan 2007
  4. Study completionOct 2011

Resources

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)
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

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.

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