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AzTrials

LeukemiaPhase 2NCT00782379

Combination Chemotherapy, Donor Stem Cell Transplant, Tacrolimus, Mycophenolate Mofetil, and Cyclophosphamide in Treating Patients With Hematologic Cancer

A Phase 2 study testing busulfan, cyclophosphamide and fludarabine phosphate in people with Leukemia and Lymphoma, run by Northside Hospital, Inc. at 1 site 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, such as fludarabine, busulfan, and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Leukemia, Lymphoma, Myelodysplastic Syndromes
What is being tested?
busulfan, cyclophosphamide and fludarabine phosphate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
Oct 2008to Apr 2012
Phase
Phase 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 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

DISEASE CHARACTERISTICS:

  • Diagnosis of one of the following high-risk hematologic malignancies:
  • Chronic myelogenous leukemia meeting one of the following criteria:
  • Disease in chronic phase and resistant to available tyrosine kinase inhibitors
  • Disease in accelerated phase
  • Disease with blast crisis that has entered into a second chronic phase after induction chemotherapy
  • Acute myelogenous leukemia meeting the following criteria:
  • Marrow blasts < 5% but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH
  • Must meet one of the following criteria:
  • Disease in second or subsequent complete remission
  • Primary induction chemotherapy failure with disease subsequently entering complete remission
  • Disease in first complete remission with poor-risk cytogenetics or arising from preceding hematological disease
  • Myelodysplastic syndrome meeting at least one of the following criteria:
  • Treatment-related
  • Monosomy 7 or complex cytogenetics
  • International prognostic scoring system score ≥ 1.5
  • Chronic myelomonocytic leukemia
  • Acute lymphocytic leukemia or lymphoblastic lymphoma meeting the following criteria:
  • Marrow blasts < 5% but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH
  • Must meet one of the following criteria:
  • Disease in second or subsequent complete remission
  • Acute lymphocytic leukemia with poor-risk karyotype [e.g., t(9;22) or bcr-abl fusion, t(4;11), or other MLL translocation] and in first complete remission
  • Chronic lymphocytic leukemia or prolymphocytic leukemia meeting both of the following criteria:
  • Previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs
  • In the opinion of the transplant physician, unlikely to benefit from reduced intensity transplantation due to the presence of one or more high-risk features (i.e., bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy)
  • Hodgkin or non-Hodgkin lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse disease) meeting the following criteria:
  • Previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation
  • In the opinion of the transplant physician, unlikely to benefit from reduced intensity transplantation due to the presence of one or more high-risk features (i.e., bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy) NOTE: A new classification scheme for adult non-Hodgkin 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.
  • No available matched related or unrelated donor OR a matched related or unrelated donor will not be available in the time frame necessary to perform a transplant
  • Availability of a first-degree relative (parent, child, sibling) matched at 3/6-5/6 loci (HLA-A, -B, -DR)
  • Donor must be willing to donate mobilized peripheral blood stem cells
  • No positive HLA crossmatch in the host-vs-graft direction or high titer donor-specific antibodies

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • Bilirubin < 2 mg/dL (unless due to hemolysis, Gilbert syndrome, or primary malignancy)
  • Creatinine < 2 mg/dL OR creatinine clearance ≥ 40 mL/min
  • Not pregnant
  • Fertile patients must use effective contraception
  • LVEF (Left ventriculr ejection fraction) ≥ 45%
  • FEV_1 and forced vital capacity ≥ 50% predicted
  • No HIV positivity
  • No debilitating medical or psychiatric illness that would preclude giving informed consent or receiving optimal treatment and follow-up

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No immunosuppressive agents ≤ 24 hours after completion of post-transplant cyclophosphamide (including steroids as antiemetics)

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Blood and Marrow Transplant Group of Georgia

    Atlanta, Georgia, 30342

Other trials in United States

About this study

Official title: A Phase II Trial of Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched Peripheral Blood Stem Cells for Patients With Hematologic Malignancies

RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving high-dose cyclophosphamide together with tacrolimus and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well combination chemotherapy works when given together with a donor stem cell transplant, followed by tacrolimus, mycophenolate mofetil, and high-dose cyclophosphamide, in treating patients with high-risk hematologic cancer.

Read the detailed description

OBJECTIVES:

Primary

  • To estimate the incidence of graft rejection and severe graft-versus-host disease after myeloablative HLA-mismatched peripheral blood stem cell transplantation (PBSCT) from first-degree relatives in patients with high-risk hematologic malignancies.

Secondary

  • To estimate overall survival, relapse, non-relapse mortality, and event-free survival in these patients.
  • To characterize additional hematologic and non-hematologic toxicities of myeloablative haploidentical PBSCT.
  • To characterize donor hematopoietic chimerism in peripheral blood stem cells after PBSCT.

OUTLINE:

  • Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -2, busulfan IV over 3 hours on days -7 to -4, and cyclophosphamide IV over 1-2 hours on days -3 and -2.
  • Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo infusion of unmanipulated peripheral blood stem cells on day 0.
  • Post-transplant regimen: Patients receive high-dose cyclophosphamide IV over 1-2 hours on days 3 and 4, tacrolimus IV over 24 hours or orally twice daily on days 5-180, and oral mycophenolate mofetil 3 times daily on days 5-34 followed by a taper to day 90. Treatment continues in the absence of disease progression or clinically significant graft-vs-host disease.

After completion of PBSCT, patients are followed periodically for 1 year.

Keywords
stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult Hodgkin lymphoma, stage III adult lymphoblastic lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III mantle cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult Hodgkin lymphoma, stage IV adult lymphoblastic lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma
Medical subject headings
Leukemia, Lymphoma, Myelodysplastic Syndromes, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Hodgkin Disease, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Follicular

What participants receive

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

  • busulfanDrug

    110 mg/m2 infused over 3 hours once daily on 4 consecutive days (Days -7, -6, -5, -4)

  • cyclophosphamideDrug

    14.5 mg/kg infused over 1-2 hours once daily on 2 consecutive days (days -3,-2).

  • fludarabine phosphateDrug

    30mg/m2 infused over 30 minutes once daily on three consecutive days (days -5, -4, -3)

  • mycophenolate mofetilDrug

    Also called CellCept

    15 mg/kg po three times a daily with a maximum dose of 3gm/day starting D+5. To be discontinued on Day +35 in the absence of clinically significant GVHD.

  • tacrolimusDrug

    Also called Prograf, FK-506

    0.03 mg/kg/day infuse over 24 hours starting on day +5 (adjusted to maintain trough level of 5-15 ng/ml). Switch to oral (twice daily divided dose) on day +21 or when able to tolerate PO. Discontinue on day +180 in the absence of clinically significant GVHD.

  • allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Also called Allo HSCT

    Patients to received unmanipulated PBSCs on Day 0

  • peripheral blood stem cell transplantationProcedure or surgery

    Also called allogeneic hematopoietic stem cell transplant

    patients to receive unmanipulated PBSCs on day 0

Study groups in NCT00782379
Study groupRoleWhat they receive
Myeloablative Haploidentical TransplantExperimentalAll patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide.
Receives: Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

What is being measured

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

  1. Incidence of Graft Rejection for Patients at Day 100

    Number of patients who experienced graft rejection by Day 100

    Measured: Day 100

  2. Number of Patients Who Experienced Severe Graft-versus-host Disease (GVHD)(Grade 3 or 4)

    Number of patients who experienced post-transplant complication (GVHD) as seen by clinical evidence

    Measured: Day 100

Secondary outcomes (9)
  1. Overall Survival at Day 100

    Overall survival is assessed, without regard to disease status, post-transplant, at Day 100.

    Measured: Day 100

  2. Non-relapse Mortality at 1 Year After Peripheral Blood Stem Cell Transplantation (PBSCT)

    Non-relapse mortality refers to whether a patient dies of causes related to something other than the primary disease.

    Measured: 1 year

  3. Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 30 Post-transplantation

    Chimerism analysis of peripheral blood mononuclear cells using PCR (polymerase chain reaction) for STR/VNTR (short tandme repeat/variable number tandem repeat) will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.

    Measured: Day 30

  4. Non-relapse Mortality at Day 100 After Peripheral Blood Stem Cell Transplantation (PBSCT)

    Measured: Day 100

  5. Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 60 Post-transplantation

    Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.

    Measured: Day 60

  6. Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 90 Post-transplantation

    Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.

    Measured: Day 90

  7. Overall Survival at 12 Months

    Overall survival, defined as a patient being alive after transplant, is without regard to disease status.

    Measured: 12 months

  8. Disease Free Survival at 12 Months

    Disease free survival refers to patients with no evidence of disease after transplant, at the 12 month time point.

    Measured: 12 months

  9. Disease Free Survival at Day 100

    Disease free survival refers to patients with no evidence of disease after transplant, at the Day 100 time point.

    Measured: Day 100

Timeline

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

  1. First posted31 Oct 2008 (estimated)
  2. Study startOct 2008
  3. Primary completionApr 2011
  4. Study completionApr 2012

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00782379
Sponsor's protocol ID
CDR0000617648
Other IDs
BMTGG-NSH-864
Status last verified
Mar 2013
First submitted
29 Oct 2008
Last updated
21 Nov 2013
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing busulfan, cyclophosphamide and fludarabine phosphate in people with Leukemia and Lymphoma, run by Northside Hospital, Inc. 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?

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 21 Nov 2013. 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 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 3 May 2013). 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?

Incidence of Graft Rejection for Patients at Day 100 (time frame: Day 100). The study lists 2 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 21 Nov 2013.

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