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CompletedNCT00782379Updated Nov 21, 2013Results posted

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

A Phase 2 interventional study of busulfan and cyclophosphamide in Leukemia, Lymphoma and Myelodysplastic Syndromes, sponsored by Northside Hospital, Inc.. Completed at 1 site in United States. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2013-11-21.

Sponsored by Northside Hospital, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
20
Allocation
Not applicable
Ages
18 Years to 60 Years
Sex
All
01

Study 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. 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.

02

Conditions studied

  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes

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
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult Hodgkin lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • noncontiguous stage II adult diffuse mixed cell lymphoma
  • noncontiguous stage II adult diffuse small cleaved cell lymphoma
  • noncontiguous stage II adult lymphoblastic lymphoma
  • noncontiguous stage II grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • accelerated phase chronic myelogenous leukemia
  • adult acute lymphoblastic leukemia in remission
  • adult acute myeloid leukemia in remission
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(15;17)(q22;q12)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • chronic myelomonocytic leukemia
  • chronic phase chronic myelogenous leukemia
  • recurrent adult acute myeloid leukemia
  • refractory chronic lymphocytic leukemia
  • relapsing chronic myelogenous leukemia
  • secondary acute myeloid leukemia
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • prolymphocytic leukemia
03

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 20 is below the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

Northside Hospital, Inc. is the lead sponsor of 27 studies on the registry; 9 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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)
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
20 participants (actual)

Study arms

  • Experimental
    Myeloablative Haploidentical Transplant

    All patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide.

    Drug: busulfan · Drug: cyclophosphamide · Drug: fludarabine phosphate · Drug: mycophenolate mofetil · Drug: tacrolimus · Procedure: allogeneic hematopoietic stem cell transplantation · Procedure: peripheral blood stem cell transplantation

Interventions

  • Drugbusulfan

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

  • Drugcyclophosphamide

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

  • Drugfludarabine phosphate

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

  • Drugmycophenolate mofetil

    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.

    Also known as: CellCept

  • Drugtacrolimus

    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.

    Also known as: Prograf, FK-506

  • Procedureallogeneic hematopoietic stem cell transplantation

    Patients to received unmanipulated PBSCs on Day 0

    Also known as: Allo HSCT

  • Procedureperipheral blood stem cell transplantation

    patients to receive unmanipulated PBSCs on day 0

    Also known as: allogeneic hematopoietic stem cell transplant

06

What researchers measure

Primary outcomes

  1. Incidence of Graft Rejection for Patients at Day 100

    Number of patients who experienced graft rejection by Day 100

    Time frame: 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

    Time frame: Day 100

Secondary outcomes

  1. Overall Survival at Day 100

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

    Time frame: 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.

    Time frame: 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.

    Time frame: Day 30

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

    Time frame: 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.

    Time frame: 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.

    Time frame: Day 90

  7. Overall Survival at 12 Months

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

    Time frame: 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.

    Time frame: 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.

    Time frame: Day 100

07

Results

Posted May 3, 2013

Participant flow

Patients were consented between 12/17/08 through 01/13/11. The transplants occured between 1/13/09 and 3/2/11

Participant flow — Overall Study
MilestoneHaploidentical Transplant
Started20
Completed20
Not completed0

Outcome measures

PrimaryIncidence of Graft Rejection for Patients at Day 100

Number of patients who experienced graft rejection by Day 100

Time frame:
Day 100
Reported as:
Number · participants
Incidence of Graft Rejection for Patients at Day 100
participantsHaploidentical Transplant
Incidence of Graft Rejection for Patients at Day 1000
PrimaryNumber 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

Time frame:
Day 100
Reported as:
Number · participants
Number of Patients Who Experienced Severe Graft-versus-host Disease (GVHD)(Grade 3 or 4)
participantsHaploidentical Transplant
Number of Patients Who Experienced Severe Graft-versus-host Disease (GVHD)(Grade 3 or 4)2
SecondaryOverall Survival at Day 100

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

Time frame:
Day 100
Reported as:
Number · participants
Overall Survival at Day 100
participantsHaploidentical Transplant
Overall Survival at Day 10017
SecondaryNon-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.

Time frame:
1 year
Reported as:
Number · participants
Non-relapse Mortality at 1 Year After Peripheral Blood Stem Cell Transplantation (PBSCT)
participantsHaploidentical Transplant
Non-relapse Mortality at 1 Year After Peripheral Blood Stem Cell Transplantation (PBSCT)2
SecondaryAchievement 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.

Time frame:
Day 30
Reported as:
Number · participants
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 30 Post-transplantation
participantsHaploidentical Transplant
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 30 Post-transplantation18
SecondaryNon-relapse Mortality at Day 100 After Peripheral Blood Stem Cell Transplantation (PBSCT)
Time frame:
Day 100
Reported as:
Number · participants
Non-relapse Mortality at Day 100 After Peripheral Blood Stem Cell Transplantation (PBSCT)
participantsHaploidentical Transplant
Non-relapse Mortality at Day 100 After Peripheral Blood Stem Cell Transplantation (PBSCT)2
SecondaryAchievement 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.

Time frame:
Day 60
Reported as:
Number · participants
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 60 Post-transplantation
participantsHaploidentical Transplant
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 60 Post-transplantation18
SecondaryAchievement 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.

Time frame:
Day 90
Reported as:
Number · participants
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 90 Post-transplantation
participantsHaploidentical Transplant
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 90 Post-transplantation13
SecondaryOverall Survival at 12 Months

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

Time frame:
12 months
Reported as:
Number · participants
Overall Survival at 12 Months
participantsHaploidentical Transplant
Overall Survival at 12 Months14
SecondaryDisease Free Survival at 12 Months

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

Time frame:
12 months
Reported as:
Number · participants
Disease Free Survival at 12 Months
participantsHaploidentical Transplant
Disease Free Survival at 12 Months7
SecondaryDisease Free Survival at Day 100

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

Time frame:
Day 100
Reported as:
Number · participants
Disease Free Survival at Day 100
participantsHaploidentical Transplant
Disease Free Survival at Day 10016

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Haploidentical Transplant—12/20 (60%)20/20 (100%)
Most frequent serious events
Showing 10 of 14
Most frequent serious events
EventHaploidentical Transplant
ColitisGastrointestinal disorders2/20
DeathGeneral disorders2/20
pneumoniaInfections and infestations2/20
Acute graft versus host diseaseImmune system disorders1/20
AscitesGastrointestinal disorders1/20
BK virusInfections and infestations1/20
Chest painCardiac disorders1/20
ConfusionNervous system disorders1/20
Hemorrhagic CystitisRenal and urinary disorders1/20
Hypoglycemia induced hemiparesisNervous system disorders1/20
Most frequent other events
Showing 10 of 155
Most frequent other events
EventHaploidentical Transplant
mucositisGastrointestinal disorders20/20
diarrheaGastrointestinal disorders19/20
fatigueGeneral disorders19/20
hyperglycemiaInvestigations19/20
nauseaGastrointestinal disorders19/20
tachycardiaCardiac disorders19/20
vomittingGastrointestinal disorders19/20
AnemiaBlood and lymphatic system disorders18/20
feverGeneral disorders18/20
hypomagnesemiaInvestigations18/20

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Haploidentical Transplant
<=18 years0
Between 18 and 65 years20
>=65 years0
Age Continuous
Age Continuous(years)Haploidentical Transplant
Mean41.75 ± 8.67
Sex: Female, Male
Sex: Female, Male(Participants)Haploidentical Transplant
Female11
Male9
Region of Enrollment
Region of Enrollment(participants)Haploidentical Transplant
United States20
08

Study locations

1 site
  • Blood and Marrow Transplant Group of Georgia
    Atlanta, Georgia 30342, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 21, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00782379
Lead sponsor
Northside Hospital, Inc.
Responsible party
Sponsor
First posted
Oct 31, 2008
Start date
Oct 2008
Primary completion
Apr 2011
Completion
Apr 2012
Results posted
May 3, 2013
Last update
Nov 21, 2013

Study contacts

Scott R. Solomon, MD
principal investigator · Blood and Marrow Transplant Group of Georgia
H. Kent Holland, MD
principal investigator · Blood and Marrow Transplant Group of Georgia
Asad Bashey, MD, PhD
principal investigator · Blood and Marrow Transplant Group of Georgia
Lawrence E. Morris, MD
principal investigator · Blood and Marrow Transplant Group of Georgia

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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