Clinical trial NCT00544115: Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other Disorders
Official title: A Phase II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation From Matched Unrelated Donors in Patients With Advanced Hematologic Malignancies and Hematological Disorders
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Precancerous/Nonmalignant Condition
Keywords: graft versus host disease
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia
untreated childhood acute lymphoblastic leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
atypical chronic myeloid leukemia
chronic myelomonocytic leukemia
juvenile myelomonocytic leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
adult acute myeloid leukemia in remission
childhood acute myeloid leukemia in remission
secondary acute myeloid leukemia
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)
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
chronic eosinophilic leukemia
chronic idiopathic myelofibrosis
chronic neutrophilic leukemia
essential thrombocythemia
polycythemia vera
Waldenstrom macroglobulinemia
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell 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 immunoblastic large cell lymphoma
recurrent adult lymphoblastic 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
splenic marginal zone lymphoma
recurrent childhood grade III lymphomatoid granulomatosis
childhood nasal type extranodal NK/T-cell lymphoma
recurrent childhood large cell lymphoma
childhood diffuse large cell lymphoma
childhood immunoblastic large cell lymphoma
recurrent childhood lymphoblastic lymphoma
Burkitt lymphoma
recurrent childhood small noncleaved cell lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
recurrent adult T-cell leukemia/lymphoma
recurrent adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
recurrent adult Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma
refractory chronic lymphocytic leukemia
refractory multiple myeloma
stage III multiple myeloma
aplastic anemia
paroxysmal nocturnal hemoglobinuria
adult acute lymphoblastic leukemia in remission
childhood acute lymphoblastic leukemia in remission
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
stage II multiple myeloma
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-10-16
Enrollment: 260
Sex: ALL
Minimum age (years): 0
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral stem cell transplant helps stop the growth of cancer or abnormal cells. It also 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 tacrolimus, methotrexate, cyclosporine, mycophenolate mofetil, and sirolimus before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well donor peripheral stem cell transplant works in treating patients with advanced hematologic cancer or other disorders.

Detailed description: OBJECTIVES:

Primary

* To evaluate hematopoietic recovery, using neutrophil and platelet engraftment as the primary criterion, in patients with advanced hematologic malignancies or other disorders undergoing allogeneic peripheral blood stem cell (PBSC) transplantation from matched unrelated donors.
* To evaluate the incidence of acute and chronic graft-versus-host-disease (GVHD) in patients undergoing allogeneic PBSC transplantation from matched unrelated donors.

Secondary

* To evaluate the impact of HLA class I and class II allele-matching on the incidence of GVHD and on the survival outcome of these patients.
* To evaluate overall survival, disease-free survival, and relapse in these patients.

OUTLINE: Patients are stratified according to type of conditioning regimen (myeloablative vs reduced-intensity myeloablative). Patients are assigned to a conditioning regimen according to diagnosis, age, disease status, prior radiotherapy, and prior autologous stem cell transplantation.

* Conditioning regimen:

  * Regimen I: Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
  * Regimen II: Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.
  * Regimen III: Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
  * Regimen IV: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
  * Regimen V: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
  * Regimen VI: Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
* Allogeneic peripheral blood stem cell (PBSC) transplantation: All patients undergo allogeneic PBSC transplantation on day 0.
* Graft-versus-host disease (GVHD) prophylaxis: Patients receive one of the following GVHD prophylaxis regimens:

  * Regimen A: Patients receive tacrolimus IV or orally on days -1 to 180 and methotrexate IV on days 1, 3, 6, and 11.
  * Regimen B: Patients receive cyclosporine IV or orally twice daily on days -1 to 180, mycophenolate mofetil IV over 2 hours or orally twice daily on days 0-27, and methotrexate IV on days 1, 3, and 6.
  * Regimen C: Patients receive tacrolimus IV continuously or orally, and oral sirolimus beginning on day -3. Patients also receive methotrexate IV on days 1, 3, and 6.

After completion of study therapy, patients are followed periodically.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of one of the following:

  * Acute lymphocytic leukemia (ALL), meeting one of the following criteria:

    * In first relapse or beyond
    * High-risk ALL, defined by any of the following:

      * Hypoploidy (≤ 44 chromosomes)
      * Pseudodiploidy with translocations or molecular evidence of t(9;22), 11q23, or t(8;14), excluding B-cell ALL
      * Elevated WBC at presentation (WBC \> 20,000/mm³ \[for patients \> 18 years of age\]; WBC \> 200,000/mm³ \[for patients 12-18 years of age\])
  * Acute myeloid leukemia (AML), meeting one of the following criteria:

    * In first complete remission
    * Failed to achieve remission
    * In first relapse or beyond
    * Secondary AML (\> 30% blasts in marrow aspirate)

      * Should receive induction chemotherapy to obtain remission, if possible, before transplant
  * Chronic myelogenous leukemia, meeting one of the following criteria:

    * In first or second chronic phase or accelerated phase
    * In blast crisis, defined as \> 30% promyelocytes plus blasts in the bone marrow
  * Myelodysplastic syndromes, including any of the following:

    * Refractory anemia with excess blasts (RAEB)
    * Chronic myelomonocytic leukemia
    * RAEB in transformation
  * Refractory non-Hodgkin lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma, or multiple myeloma

    * Received and failed front-line therapy, high-dose therapy and autologous stem cell transplantation, or salvage therapy
  * Myeloproliferative disorders/myelofibrosis may be allowed on a case by case basis
  * Severe aplastic anemia, paroxysmal nocturnal hemoglobinuria, or any other hematologic disorder requiring transplantation
* Patients \> 55 years of age with hematologic diseases treatable by allogeneic stem cell transplantation who are not eligible for IRB 99190 are eligible
* No uncontrolled CNS involvement of disease
* No matched (6/6) related donor available
* HLA-identical unrelated donor available

  * HLA-phenotypically identical for HLA-A and HLA-B alleles and identical for DRB1 alleles by DNA typing for both class I and class II antigens

    * Allele mismatch for HLA class I (i.e., B 2701 vs B 2702) allowed if no alternative donors
    * Allele mismatch for class II (i.e., DRB1 0401 vs 0402) or minor mismatch for class I cross reactive group (CREG) (i.e., A 2 vs A 28) allowed in patients ≤ 35 years of age requiring urgent transplant

PATIENT CHARACTERISTICS:

* Karnofsky performance status 50-100%
* Life expectancy \> 8 weeks
* LVEF ≥ 45% at rest
* AST ≤ 2 times normal (unless liver function abnormality is due to underlying disease)
* Total bilirubin \< 1.5 times normal (unless liver function abnormality is due to underlying disease)
* Creatinine ≤ 1.5 times normal OR creatinine clearance ≥ 60 mL/min
* DLCO ≥ 40% of predicted (corrected for hemoglobin)
* No coexisting medical problem that would significantly increase the risk of the transplant procedure
* HIV negative
* Not pregnant

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Primary outcomes:
measure: Neutrophil Engraftment - The Days Till ANC Recovery
timeFrame: Up to 180 days post transplant
Secondary outcomes:
measure: Two-year Overall Survival
timeFrame: Up to 2 years post transplant
Other outcomes:
Locations:
Study officials:
affiliation: City of Hope Comprehensive Cancer Center
name: Auayporn P. Nademanee, MD
role: STUDY_CHAIR
References: