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LeukemiaPhase 2NCT00053196

Donor Stem Cell Transplant in Treating Patients With Relapsed Hematologic Cancer

A Phase 2 study testing anti-thymocyte globulin, G-CSF and busulfan in people with Leukemia and Lymphoma, run by Alliance for Clinical Trials in Oncology at 12 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 low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops 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, Multiple Myeloma
What is being tested?
anti-thymocyte globulin, G-CSF and busulfan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
82 participants
Where
12 sitesUnited States
Study dates
Dec 2002to Aug 2010
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:

  • Histologically confirmed hematologic malignancy, including one of the following:
  • Chronic lymphocytic leukemia (CLL)
  • Absolute lymphocytosis greater than 5,000/mm^3
  • Lymphocytes must appear morphologically mature with less than 55% prolymphocytes
  • Lymphocyte phenotype with expression of CD19 and CD5
  • Prolymphocytic leukemia (PLL)
  • Morphologically confirmed
  • Absolute lymphocytosis greater than 5,000/mm^3
  • More than 55% prolymphocytes
  • Non-Hodgkin's lymphoma or Hodgkin's lymphoma
  • Any WHO histologic subtype allowed except mantle cell lymphoma
  • Core biopsies allowed if they contain adequate tissue for primary diagnosis and immunophenotyping
  • No bone marrow biopsy as the sole diagnostic means for follicular lymphoma
  • Multiple myeloma
  • Active disease requiring treatment
  • Durie-Salmon stage I, II, or III
  • Acute myeloid leukemia
  • Documented control (i.e., less than 10% bone marrow blasts and no circulating blasts)
  • Myelodysplastic syndromes
  • Documented disease by WHO criteria
  • Must have evidence of relapse/progression at least 6 months after prior high-dose chemotherapy with autologous hematopoietic stem cell support
  • Absence of CD23 expression for CLL or PLL allowed provided there is no morphologic evidence of mantle cell lymphoma
  • Availability of any of the following donor types:
  • HLA-identical sibling (6/6)
  • 9/10 matched related donor by high-resolution molecular typing at HLA A, B, C, DRB1, and DQB1 loci
  • Only a single mismatch at one class I or II allele allowed
  • 10/10 matched unrelated donor by high-resolution molecular typing at HLA A, B, C, DRB1, and DQB1 loci
  • No syngeneic donors

PATIENT CHARACTERISTICS:

Age

  • Under 70

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin no greater than 3 times upper limit of normal (ULN)
  • AST no greater than 3 times ULN

Renal

  • Creatinine clearance at least 40 mL/min

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

  • See Disease Characteristics

Chemotherapy

  • See Disease Characteristics
  • More than 4 weeks since prior chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • More than 4 weeks since prior radiotherapy

Surgery

  • More than 4 weeks since prior surgery

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263-0001

  • 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

  • Rebecca and John Moores UCSD Cancer Center

    La Jolla, California, 92093-0658

  • Beebe Medical Center

    Lewes, Delaware, 19958

  • 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

  • Siteman Cancer Center at Barnes-Jewish Hospital

    St Louis, Missouri, 63110

  • 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

Other trials in United States

About this study

Official title: Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation For Patients With Disease Relapse Or Myelodysplasia After Prior Autologous Transplantation

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving immunosuppressive therapy after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well donor bone marrow or peripheral stem cell transplant works in treating patients with relapsed hematologic cancer after treatment with chemotherapy and autologous stem cell transplant.

Read the detailed description

OBJECTIVES:

  • Determine the feasibility of non-myeloablative allogeneic hematopoietic stem cell transplantation by demonstrating that the risk of treatment-related mortality during the first 6 months is an acceptable rate of less than 40% in patients with relapsed hematologic malignancies after prior high-dose chemotherapy and autologous stem cell transplantation.
  • Determine the response rates (disease-specific partial and complete response) in patients treated with this regimen.
  • Determine the 6-month and 12-month probabilities of response in patients treated with this regimen.
  • Determine the distribution of time-to-progression in patients responding to this regimen.
  • Determine the percent donor chimerism in patients treated with this regimen.
  • Determine the risk of acute and chronic graft-vs-host disease in patients treated with this regimen.
  • Determine the toxic effects of this regimen in these patients.
  • Determine the disease-free and overall survival of patients treated with this regimen.

OUTLINE: This is an open-label study.

  • Preparative Regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours every 6 hours (for a total of 8 doses) on days -4 and -3.
  • Graft vs Host Disease (GVHD) Prophylaxis: Patients who have an HLA-identical donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 90 followed by a taper^* until day 150 and methotrexate IV on days 1, 3, and 6. Patients with a matched related or matched unrelated donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 180 followed by a taper^* as tolerated; methotrexate IV on days 1, 3, 6, and 11; oral mycophenolate mofetil twice daily on days -2 to 60 followed by a taper; and rabbit anti-thymocyte globulin IV over 4-6 hours on days -4 to -1 (for a total of 4 doses).

NOTE: *Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is less than 50% at day 60 or patient has progressive disease

  • Allogeneic Stem Cell Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on days 0 and 1. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.
  • Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an HLA-identical donor), patients with stable or progressive disease and no active GVHD may receive up to 3 DLIs every 8 weeks.

Patients are followed within 2-3 months, every 3 months for 2 years, and then every 6 months for 3 years.

Being tested
anti-thymocyte globulin, G-CSF, busulfan, fludarabine phosphate, methotrexate
Keywords
refractory chronic lymphocytic leukemia, prolymphocytic leukemia, recurrent adult Hodgkin lymphoma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, previously treated myelodysplastic syndromes, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult Burkitt lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, secondary myelodysplastic syndromes, de novo myelodysplastic syndromes, recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia
Medical subject headings
Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Myeloproliferative Disorders, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Prolymphocytic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • anti-thymocyte globulinBiological

    2.5mg/kg/day IV infusion over 6 hrs x 4 doses Days -4 to -1 (for MUD and 9/10 related donor transplants only)

  • G-CSFBiological

    Also called filgrastim

    5 ug/kg/day subQ injection Day 7 until ANC> 1000/uL for 3 consec days

  • busulfanDrug

    0.8mg/kg IV infusion over 2 hrs q 6 hrs x 8 doses Days -4 thru -3

  • fludarabine phosphateDrug

    30 mg/sq m/day IVBP over 30 min Days -7 thru -3

  • methotrexateDrug

    5 mg/sq m/day IV infusion Days 1, 3, \& 6 for HLA-identical donor transplants and Days 1, 3, 6, \& 11 for MUD \& 9/10 related donor transplants

  • mycophenolate mofetilDrug

    15mg/kg PO bid Day -2 to Day 60, then taper as tolerated (for MUD and 9/10 related donor transplants only)

  • tacrolimusDrug

    target serum level is 5-10 ng/mL. Start with 0.03mg/kg PO bid Day -1 to Day 90, then taper thru Day 150 for HLA identical donor transplants and Day -1 to Day 180 then taper for MUD and 9/10 related donor transplants

  • allogeneic cell transplantationProcedure or surgery

    2,000,000-8,000,000 CD34+ cells total via infusion Days 0 and 1

  • allopurinolDrug

    300 mg/day PO Days -8 thru -1

Study groups in NCT00053196
Study groupRoleWhat they receive
Non myeloblative allogeneic transplantExperimentalNon myeloblative allogeneic hematopoietic cell transplantation after prior autologous transplantation
Receives: Biological: anti-thymocyte globulin; Biological: G-CSF; Drug: busulfan; Drug: fludarabine phosphate; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: allogeneic cell transplantation; Drug: allopurinol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Treatment-related mortality

    Measured: 6 months post transplant

Secondary outcomes (4)

  1. Per cent donor chimerism

    Measured: 30, 60, 90, 180 days post transplant

  2. Disease-free survival

    Measured: 12 months up to 5 years post study entry

  3. Graft-versus-host disease incidence

    Measured: 6 months post transplant

  4. Response Rates

    Measured: 6 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2003 (estimated)
  2. Study startDec 2002
  3. Primary completionNov 2006
  4. Study completionAug 2010

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
82 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00053196
Sponsor's protocol ID
CALGB-100002
Other IDs
U10CA031946, CALGB-100002, CDR0000269301
Status last verified
Jun 2016
First submitted
27 Jan 2003
Last updated
1 Jul 2016
Results posted
No
Data monitoring committee
No

Publications

  • Bashey A, Owzar K, Johnson JL, Edwards PS, Kelly M, Baxter-Lowe LA, Devine S, Farag S, Hurd D, Ball E, McCarthy P, Lister J, Shea TC, Linker C. Reduced-intensity conditioning allogeneic hematopoietic cell transplantation for patients with hematologic malignancies who relapse following autologous transplantation: a multi-institutional prospective study from the Cancer and Leukemia Group B (CALGB trial 100002). Biol Blood Marrow Transplant. 2011 Apr;17(4):558-65. doi: 10.1016/j.bbmt.2010.07.015. Epub 2010 Jul 30.

    PubMed 20674758

  • Bashey A, Owzar K, Johnson JL, et al.: Reduced-intensity allogeneic transplantation after failure of autologous transplantation: a prospective multi-center CALGB study. [Abstract] Blood 108 (11): A-3122, 2006.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing anti-thymocyte globulin, G-CSF and busulfan in people with Leukemia and Lymphoma, run by Alliance for Clinical Trials in Oncology at 12 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 1 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 12 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 (time frame: 6 months 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 NCT00053196, which also lists 2 linked publications.

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 1 Jul 2016.

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