Know Cancer

or
forgot password

A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched Bone Marrow for Patients With Hematologic Malignancies


Phase 2
N/A
70 Years
Open (Enrolling)
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

Thank you

Trial Information

A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched Bone Marrow for Patients With Hematologic Malignancies


OBJECTIVES:

- Determine transplant-related mortality, risk of relapse, and progression-free survival
of patients with standard- or high-risk hematologic malignancies undergoing
nonmyeloablative conditioning comprising fludarabine, cyclophosphamide, and total-body
irradiation followed by HLA-haploidentical allogeneic bone marrow transplantation.

- Determine donor hematopoietic chimerism in patients' peripheral blood at 30, 60, and
180 days after transplantation.

- Determine hematologic and nonhematologic toxic effects of this regimen in these
patients.

- Determine, when feasible, surface expression of HLA molecules and death receptors,
sensitivity to cytotoxic lymphocytes, and expression of anti-apoptotic genes (e.g.,
Bcl-2, Bcl-xL, X-IAP, and c-FLIP) in cancer cells from patients who relapse after
treatment with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to risk of relapse
(standard [defined as ≤ 30% risk] vs high [defined as ≥ 70% risk]).

- Nonmyeloablative conditioning regimen: Patients receive fludarabine IV over 30 minutes
on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -6 and -5. Patients
undergo total body irradiation on day -1.

- Allogeneic bone marrow transplantation: Patients undergo donor bone marrow infusion on
day 0.

- Post-transplantation therapy: Patients receive cyclophosphamide IV over 1-2 hours on
days 3 and 4.

- Graft-vs-host disease prophylaxis: Beginning on day 5, patients receive oral
mycophenolate mofetil 3 times daily until day 35 and tacrolimus IV (then changing to
orally) twice daily until day 180.

Treatment continues in the absence of disease progression.

After completion of study transplantation, patients are followed on days 30, 60, 100, and
180; at 1 year; and then annually for 4 additional years.

PROJECTED ACCRUAL: A total of 75-100 patients will be accrued for this study within 3-4
years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following hematologic malignancies:

- Acute leukemia

- In second or subsequent complete remission (CR), as defined by absence of
abnormal blast population by flow cytometry

- In first CR with any of the following poor-risk cytogenetic features:

- Alteration of chromosome 5 or 7

- Multiple abnormalities

- Philadelphia chromosome positive

- Chronic phase chronic myelogenous leukemia (CML)

- In first chronic phase and refractory to interferon alfa or imatinib
mesylate

- In second or subsequent chronic phase

- Chronic lymphocytic leukemia, meeting 1 of the following criteria:

- Received prior chemotherapy with a nucleoside analog and had remission
lasting < 6 months

- Received 1 prior therapy and has any of the following high-risk features:

- Cytogenetic abnormalities of 17p, 11q

- Mutations of the Zap70 gene

- Somatically unmutated immunoglobulin heavy chain variable region genes

- Hodgkin's lymphoma

- Ineligible for autologous stem cell transplantation (SCT) due to any of the
following exclusion factors:

- LVEF < 45%

- FEV_1 or FVC < 50% of predicted (75% of predicted in patients with
prior thoracic or mantle radiotherapy)

- Total bilirubin > 2.0 mg/dL (unless documented Gilbert's disease)

- Creatinine > 2.0 mg/dL

- Non-Hodgkin's lymphoma (NHL)

- Low-grade NHL allowed provided patient had a remission duration of < 1 year
after administration of any established, multi-agent chemotherapy regimen
(e.g., CVP, CHOP, or rituximab in combination with CHOP)

- Intermediate- or high-grade NHL allowed provided patient is ineligible for
autologous SCT according to the criteria listed above

- Multiple myeloma

- Myelodysplastic syndromes

- Paroxysmal nocturnal hemoglobinuria

- Chronic myeloproliferative disorders other than CML, including any of the
following:

- Chronic myelomonocytic leukemia

- Agnogenic myeloid metaplasia (or myeloid metaplasia with myelofibrosis),
with hemoglobin < 10 g/dL OR WBC < 4,000/mm^3 or > 30,000/mm^3

- Polycythemia vera or essential thrombocythemia in "spent" phase, with a
history of 2 of the following:

- Marrow fibrosis

- Splenomegaly

- Cytopenia (i.e., absolute neutrophil count < 1,500/mm^3, platelet
count < 100,000/mm^3, hemoglobin < 10 g/dL)

- Polycythemia vera or essential thrombocythemia with transformation to
myelodysplastic syndromes or acute myeloid leukemia (requires treatment to
achieve < 20% blasts in marrow)

- No smoldering myeloma

- Patients with acute myeloid leukemia or myelodysplastic syndromes must have had
comprehensive cytogenetic evaluation of bone marrow specimen during active disease

- Ineligible for or refused bone marrow transplantation from an HLA-matched sibling or
unrelated donor

- Ineligible for or refused autologous SCT

- Must have an HLA mismatched (i.e., 3/6, 4/6, or 5/6) related (first-degree relative)*
donor available

- Donor ≥ 18 years of age NOTE: *Patients with an inherited recombinant HLA
haplotype may receive marrow from the parent in whose gamete the recombination
occurred

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

- 6 months to 70 years

Performance status

- ECOG 0-1

Life expectancy

- Not specified

Hematopoietic

- See Disease Characteristics

Hepatic

- See Disease Characteristics

- Bilirubin < 3.1 mg/dL

Renal

- See Disease Characteristics

Cardiovascular

- See Disease Characteristics

- LVEF ≥ 35%

Pulmonary

- See Disease Characteristics

- FEV_1 or FVC ≥ 40% of predicted in patients without prior thoracic or mantle
radiotherapy (60% of predicted in patients with prior thoracic or mantle
radiotherapy)

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- Geographically accessible

- No debilitating medical or psychiatric illness that would preclude giving informed
consent or receiving optimal treatment or follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

- No prior transfusions from donor

Chemotherapy

- See Disease Characteristics

Endocrine therapy

- Not specified

Radiotherapy

- See Disease Characteristics

Surgery

- Not specified

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Transplant-related mortality at 60 days, 6 months, 1 and 2 years

Outcome Time Frame:

2 years

Safety Issue:

No

Principal Investigator

Ephraim J. Fuchs, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

J0457 CDR0000440990

NCT ID:

NCT00134004

Start Date:

October 2004

Completion Date:

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • adult acute lymphoblastic leukemia in remission
  • adult acute myeloid leukemia in remission
  • childhood acute lymphoblastic leukemia in remission
  • childhood acute myeloid leukemia in remission
  • childhood chronic myelogenous leukemia
  • chronic phase chronic myelogenous leukemia
  • refractory chronic lymphocytic leukemia
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • 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 idiopathic myelofibrosis
  • chronic myelomonocytic leukemia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • noncontiguous stage II adult Burkitt 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 immunoblastic large 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
  • noncontiguous stage II marginal zone lymphoma
  • noncontiguous stage II small lymphocytic lymphoma
  • recurrent adult Burkitt 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 adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent/refractory childhood Hodgkin lymphoma
  • recurrent childhood large cell lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • recurrent childhood small noncleaved cell lymphoma
  • nodal marginal zone B-cell lymphoma
  • 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
  • refractory multiple myeloma
  • relapsing chronic myelogenous leukemia
  • secondary myelodysplastic syndromes
  • splenic marginal zone lymphoma
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • stage III adult Burkitt 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 adult Hodgkin lymphoma
  • stage III adult immunoblastic large cell 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 III marginal zone lymphoma
  • polycythemia vera
  • essential thrombocythemia
  • stage III small lymphocytic lymphoma
  • stage IV mantle cell lymphoma
  • stage IV marginal zone lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV adult Burkitt 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 immunoblastic large cell lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV small lymphocytic lymphoma
  • stage IV adult Hodgkin lymphoma
  • childhood myelodysplastic syndromes
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

Hahnemann University HospitalPhiladelphia, Pennsylvania  19102-1192
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Blood and Marrow Transplant Program at Northside HospitalAtlanta, Georgia  30342