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Reduced Intensity Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Patients With Hematologic Malignancies


Phase 2
40 Years
72 Years
Not Enrolling
Both
Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

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Trial Information

Reduced Intensity Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Patients With Hematologic Malignancies


OBJECTIVES:

- To evaluate the safety and toxicity of a reduced-intensity conditioning regimen
followed by allogeneic bone marrow or peripheral blood stem cell transplantation from
an HLA-matched unrelated donor in patients with high-risk hematologic malignancies.

- To evaluate engraftment by peripheral blood chimerism analysis.

- To determine the incidence and severity of acute and chronic graft-versus-host disease
following the transplant.

- To examine the possibility of controlling hematologic malignancies by induction of a
graft-versus-leukemia/tumor effect.

- To determine the disease-free survival, relapse, transplant-related mortality, and
death from all causes.

OUTLINE:

- Reduced-intensity conditioning regimen: Patients receive 1 of 2 conditioning regimens
according to diagnosis.

- Regimen 1 (acute leukemia, myelodysplastic syndromes, myeloproliferative syndrome,
or chronic myelogenous leukemia): Patients receive fludarabine phosphate IV over
30 minutes and busulfan IV over 3 hours on days -6 to -3 or orally 4 times daily
on days -7 to -3.

- Regimen 2 (lymphoproliferative malignancies): Patients receive fludarabine
phosphate IV over 30 minutes and cyclophosphamide IV over 1 hour on days -5 to -3.
Patients with CD20+ malignancies also receive rituximab IV over 4-6 hours on days
-13, -6, 1, and 8.

- Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell
transplantation on day 0.

- Graft-versus-host disease (GVHD) prophylaxis: Patients receive low-dose alemtuzumab
subcutaneously on days -11 to -9 and tacrolimus IV over 24 hours beginning on day -3
and then orally twice daily beginning on day 14 and continuing until day 60, followed
by a taper until day 180 in the absence of clinically significant GVHD. Patients also
receive methotrexate on days 1, 3, and 6.

Patients who exhibit persistent mixed chimerism or disease relapse/progression despite full
withdrawal of immunosuppression may receive up to 3 donor lymphocyte infusions.

Blood samples are taken on days 30, 60, and 100 and then every 4 weeks thereafter for
chimerism studies by PCR analysis.

After completion of study therapy, patients are followed periodically for up to 60 months.

Inclusion Criteria


- Diagnosis of one of the following hematological malignancies:

- CML, with 1 of the following:

- In first CP AND failed imatinib mesylate therapy, defined as failure to
obtain a hematologic remission at 3 months or a major cytogenetic response
(i.e., Ph+ cells < 35%) at 6 months or demonstrated clonal evolution or
disease progression during therapy

- In accelerated phase with < 15% blasts

- In blast crisis that has entered into a second CP following induction
chemotherapy

- AML, with 1 of the following:

- In second or subsequent complete remission (CR) (i.e., < 5% blasts by
morphology, no residual leukemia by flow cytometry, and absence of
cytogenetic abnormalities)

- Failed primary induction chemotherapy, but subsequently entered into a CR
with ≤ 2 subsequent re-induction chemotherapy treatment(s)

- In first CR with intermediate-risk or poor-risk cytogenetics

- ALL with 1 of the following:

- In second or subsequent CR

- In first CR AND presence of t(9;22)

- MDS, with the following:

- High-risk disease, defined by IPSS score of ≥ 1.5 at diagnosis AND meets 1
of the following criteria:

- ≤ 10% blasts at diagnosis

- In morphologic CR (< 5% blasts) following cytoreductive chemotherapy

- CMML, with 1 of the following:

- ≤ 10% blasts at diagnosis

- In morphologic CR (< 5% blasts) following cytoreductive chemotherapy

- CLL/PLL with the following:

- Rai stage I-IV disease

- Failed ≥ 1 prior chemotherapy regimen (including fludarabine phosphate) or
ASCT

- Documented chemosensitive or stable, non-bulky disease prior to transplant,
defined as < 20% bone marrow involvement AND lymph node size < 3 cm in
axial diameter

- No bulky tumor masses, elevated lactate dehydrogenase (LDH), B symptoms, or
progressive disease prior to transplant

- Low-grade non-Hodgkin lymphoma (NHL) (i.e., small lymphocytic lymphoma,
follicular center lymphoma [grade 1 or 2], marginal zone lymphoma, or B-cell
lymphoma), with the following criteria:

- Failed ≥ 1 prior chemotherapy regimen or ASCT

- Documented chemosensitive or stable, non-bulky disease prior to transplant,
defined as < 20% bone marrow involvement AND lymph node size < 3 cm in
axial diameter

- Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and
involved-field radiotherapy are not considered a prior regimen)

- No bulky tumor masses, elevated LDH, B symptoms, or progressive disease
prior to transplant

- Mantle cell lymphoma, with the following:

- Failed to achieve remission or recurred after either conventional
chemotherapy or ASCT

- Responsive or stable disease to most recent prior therapy

- No bulky tumor masses, elevated LDH, B symptoms, or progressive disease
prior to transplant

- Intermediate-grade NHL (i.e., follicular center lymphoma [grade 3] or diffuse
large cell lymphoma), meeting the following criteria:

- Failed to achieve remission or recurred after either conventional
chemotherapy or ASCT

- Documented chemosensitive, non-bulky disease prior to transplant, defined
as at least a partial remission to salvage chemotherapy (≥ 50% reduction in
diameter of all disease sites)

- No bulky tumor masses, elevated LDH, B symptoms, or progressive disease
prior to transplant

- Hodgkin lymphoma, with the following:

- Relapsed after prior ASCT OR after ≥ 2 combination chemotherapy regimens
and ineligible for ASCT

- Documented chemosensitive, non-bulky disease prior to transplant, defined
as at least a partial remission to salvage chemotherapy (≥ 50% reduction in
diameter of all disease sites)

- No bulky tumor masses, elevated LDH, B symptoms, or progressive disease
prior to transplant

- Peripheral T-cell NHL, with the following:

- Failed to achieve remission or recurred after either conventional
chemotherapy or ASCT

- Documented chemosensitive, non-bulky disease prior to transplant, defined
as at least a partial remission to salvage chemotherapy (≥ 50% reduction in
diameter of all disease sites)

- No bulky tumor masses, elevated LDH, B symptoms, or progressive disease
prior to transplant

- Myeloproliferative syndrome with poor risk features, meeting 1 of the following
criteria:

- < 55 years old AND Lille score of 1

- Lille score of 2

- HgB < 10 g/dL AND abnormal karyotype

- High-risk disease, with 1 of the following:

- Age 40-72 years

- Any age AND deemed to be at significantly increased risk of morbidity and death
following a standard, myeloablative unrelated donor stem cell transplant (e.g.,
received extensive prior therapy, including ASCT)

- HLA-matched unrelated donor available, with 1 of the following:

- 8/8 match at HLA-A, B, C, or DR loci by high-resolution genotyping

- Single allelic mismatch at either the HLA-B or HLA-C loci donor by
high-resolution molecular typing

- No single allelic mismatch at HLA-A or HLA-DR loci

- KPS 80-100%

- Adapted weighted Charlson Comorbidity Index < 3

- Serum creatinine ≤ 2.0 mg/dL

- AST or ALT < 3 times upper limit of normal (ULN)

- Total bilirubin < 1.5 times ULN

- LVEF ≥ 45%

- DLCO > 50%

- No hypoxia at rest with oxygen saturation < 92% on room air (corrected with
bronchodilator therapy)

- No other severe pulmonary function abnormalities

- No HIV infection

- No active hepatitis B or C infection that, in the opinion of a gastroenterologist or
the transplant committee, places the patient at moderate to high risk for developing
severe hepatic disease

- No active opportunistic infection (e.g., fungal pneumonia, tuberculosis, or viral
infection)

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Survival at day 100

Outcome Description:

Survival at Day 100

Outcome Time Frame:

100 day

Safety Issue:

No

Principal Investigator

Scott R. Solomon, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Blood and Marrow Transplant Group of Georgia

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000630617

NCT ID:

NCT00818961

Start Date:

May 2005

Completion Date:

March 2012

Related Keywords:

  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • accelerated phase chronic myelogenous leukemia
  • adult acute lymphoblastic leukemia in remission
  • adult acute myeloid leukemia in remission
  • adult AML with 11q23 (MLL) abnormalities
  • blastic phase chronic myelogenous leukemia
  • chronic myelomonocytic leukemia
  • chronic phase chronic myelogenous leukemia
  • prolymphocytic leukemia
  • recurrent adult T-cell leukemia/lymphoma
  • refractory chronic lymphocytic leukemia
  • relapsing chronic myelogenous leukemia
  • secondary acute myeloid leukemia
  • stage I adult T-cell leukemia/lymphoma
  • stage I chronic lymphocytic leukemia
  • stage II adult T-cell leukemia/lymphoma
  • stage II chronic lymphocytic leukemia
  • stage III adult T-cell leukemia/lymphoma
  • stage III chronic lymphocytic leukemia
  • stage IV adult T-cell leukemia/lymphoma
  • stage IV chronic lymphocytic leukemia
  • recurrent adult Hodgkin lymphoma
  • anaplastic large cell lymphoma
  • angioimmunoblastic T-cell lymphoma
  • cutaneous B-cell non-Hodgkin lymphoma
  • recurrent cutaneous T-cell NHL
  • stage I cutaneous T-cell NHL
  • stage II cutaneous T-cell NHL
  • stage III cutaneous T-cell NHL
  • stage IV cutaneous T-cell NHL
  • extranodal marginal zone B-cell lymphoma of mucosal tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • contiguous st II adult diffuse large cell lymphoma
  • contiguous st II adult diffuse mixed cell lymphoma
  • contiguous st II adult diffuse sm cleaved cell lymphoma
  • contiguous st II grade 1 follicular lymphoma
  • contiguous st II grade 2 follicular lymphoma
  • contiguous st II grade 3 follicular lymphoma
  • contiguous st II mantle cell lymphoma
  • contiguous st II marginal zone lymphoma
  • contiguous st II small lymphocytic lymphoma
  • stage I adult diffuse large cell lymphoma
  • stage I adult diffuse mixed cell lymphoma
  • stage I adult diffuse small cleaved cell lymphoma
  • stage I grade 1 follicular lymphoma
  • stage I grade 2 follicular lymphoma
  • stage I grade 3 follicular lymphoma
  • stage I mantle cell lymphoma
  • stage I marginal zone lymphoma
  • stage I small lymphocytic lymphoma
  • noncontiguous st II adult diffuse large cell lymphoma
  • noncontiguous st II adult diffuse mixed cell lymphoma
  • noncontiguous st II adult diffuse sm cleaved cell lymphoma
  • noncontiguous st II grade 1 follicular lymphoma
  • noncontiguous st II grade 2 follicular lymphoma
  • noncontiguous st II grade 3 follicular lymphoma
  • noncontiguous st II mantle cell lymphoma
  • noncontiguous st II marginal zone lymphoma
  • noncontiguous st II small lymphocytic lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage III adult diffuse small cleaved cell 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 III marginal zone lymphoma
  • stage III small lymphocytic 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 grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV mantle cell lymphoma
  • stage IV marginal zone lymphoma
  • stage IV small lymphocytic lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult gr III lymphomatoid granulomatosis
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • de novo MDS
  • previously treated MDS
  • secondary myelodysplastic syndromes
  • Waldenstrom macroglobulinemia
  • myelodysplastic/myeloproliferative disease
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Blood and Marrow Transplant Group of GeorgiaAtlanta, Georgia  30342-1601