This trial has been completed.

Conditions chronic myeloproliferative disorders, leukemia, lymphoma, multiple myeloma and plasma cell neoplasm, myelodysplastic syndromes
Treatments allogeneic bone marrow transplantation, allogeneic hematopoietic stem cell transplantation, nonmyeloablative allogeneic hematopoietic stem cell transplantation, peripheral blood stem cell transplantation
Phase phase 2
Sponsor Wake Forest University Health Sciences
Start date February 2007
End date February 2014
Trial size 66 participants
Trial identifier NCT00453206, CCCWFU-29506, CDR0000538185, IRB00001366


RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and melphalan, before a donor peripheral stem cell transplant or bone marrow 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, mycophenolate mofetil, and antithymocyte globulin before and after transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer or abnormal cells as not belonging in the patient's body and destroy them (graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.

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

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Primary purpose treatment
Masking no masking

Primary Outcomes

Treatment-related Mortality Within the First 6 Months After Transplantation
time frame: 6 months

Secondary Outcomes

Complete Response
time frame: monthly
Overall Survival
time frame: monthly
Disease-free Survival
time frame: monthly
Graft-versus-host Disease
time frame: monthly
Iron Status at the Time of Transplantation
time frame: baseline
Quality of Life at the Time of Transplantation
time frame: baseline
Treatment-related Mortality at 100 Days After Transplantation
time frame: 100 days

Eligibility Criteria

All participants up to 70 years old.

Inclusion Criteria: - Histologically confirmed hematological disease, including any of the following: - Chronic lymphocytic leukemia - Absolute lymphocytosis > 5,000/µL - Morphologically mature lymphocytes with < 55% prolymphocytes - Lymphocyte phenotype with expression of CD19 and CD5 - Absence of CD23 expression allowed provided disease is morphologically distinguished from mantle cell lymphoma - Prolymphocytic leukemia - Absolute lymphocytosis > 5,000/µL - Morphologically mature lymphocytes with > 55% prolymphocytes - Non-Hodgkin's or Hodgkin's lymphoma - Any WHO classification histologic subtype - Diagnosis by core biopsy allowed provided there is adequate tissue for diagnosis and immunophenotyping - Diagnosis by bone marrow biopsy not acceptable for follicular lymphomas - Multiple myeloma - Has received ≥ 1 prior treatment regimen - Has a partial response or greater by the Blade Criteria - Patients who achieved complete remission are eligible - Acute myeloid leukemia - Documented control (i.e., < 10% bone marrow blasts and no circulating blasts) - Myelodysplastic syndromes - Documented disease as defined by WHO or French-American-British Cooperative group criteria - Chronic myelogenous leukemia - Patients with atypical chronic myelogenous leukemia (i.e., absent Philadelphia chromosome) are eligible - Polycythemia vera - Documented disease as defined by WHO criteria (i.e., A1 + A2, and any other category A, OR A1 + A2, and any 2 category B): - A1: Total red blood cell mass > 25% above mean normal predicted value OR hemoglobin > 18.5 g/dL in males, 16.5 g/dL in females (hematocrit ≥ 60% in males or ≥ 56% in females) - A2: No cause of secondary erythrocytosis (absence of familial erythrocytosis, no elevation of epoetin alfa [EPO] due to hypoxia, high oxygen affinity hemoglobin, truncated EPO receptor, or inappropriate ectopic EPO production) - A3: Splenomegaly - A4: Clonal genetic abnormality other than the Philadelphia chromosome - A5: Endogenous erythroid colony formation in vitro - B: Platelet count > 400,000/mm³, WBC > 12,000/mm³, bone marrow biopsy with prominent erythroid and megakaryocytic proliferation, and low serum EPO - Chronic idiopathic myelofibrosis - Documented disease as defined by WHO criteria - Must have a HLA-identical donor, a matched unrelated donor, or a HLA 9/10 related donor meeting the following criteria: - HLA-identical sibling (6/6) - Serologic typing for class I (A, B) - Molecular typing for class II (DRB1) - 9/10 matched related donor - High-resolution molecular typing at HLA-A, B, C, DRB1, and DQB1 - Only a single mismatch at one class I or II allele allowed - 10/10 matched unrelated donor - Molecular identity at HLA-A, B, C, DRB1, and DQB1 by high-resolution typing - Syngeneic donors are not eligible - Creatinine clearance ≥ 40 mL/min - Bilirubin ≤ 3 times upper limit of normal (ULN) - AST ≤ 3 times ULN - DLCO ≥ 40% with no symptomatic pulmonary disease - LVEF ≥ 30% by cardiac MRI or echocardiogram with no symptomatic cardiac disease - Fertile patients willing to use effective contraception Exclusion Criteria: - Uncontrolled diabetes mellitus - Active serious infection - Known hypersensitivity to E. coli-derived products - Known HIV positivity - History of another malignancy*, meeting the following criteria: - Non-skin malignancy or melanoma within the past 5 years - Concomitant malignancy that has not been curatively treated - NOTE: *However, cancer survivors who have undergone potentially curative therapy for a prior malignancy at least 5 years before enrollment and are deemed at low risk of < 30% for recurrence by their treating physicians is considered - Pregnant or nursing

Additional Information

Official title Reduced Intensity Allogeneic Hematopoietic Cell Transplantation for Patients With Hematological Diseases
Description OBJECTIVES: Primary - Determine the feasibility (i.e., risk of treatment-related mortality during the first 6 months after transplantation) of administering reduced-intensity allogeneic hematopoietic stem cell transplantation to patients with hematologic cancer or other diseases. Secondary - Determine the response rate (partial and complete response), 6- and 12-month probabilities of response, and time to progression in patients treated with this regimen. - Determine the risk of acute and chronic graft-versus-host disease in patients treated with this regimen. - Determine other toxicities of this regimen in these patients. - Determine the overall survival and disease-free survival of patients treated with this regimen. - Determine the impact of iron status on overall and disease-free survival. - Determine the influence of quality of life (at time of transplantation) on overall survival. OUTLINE: - Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3. Patients also receive busulfan IV over 2 hours every 6 hours on days -4 and -3 or melphalan IV over 2 hours on day -3. - Graft-versus-host disease (GVHD) prophylaxis: Patients with matched related donors receive oral tacrolimus twice daily on days -1 to 90 followed by a taper until day 180. Patients also receive methotrexate IV on days 1, 3, and 6. Patients with matched unrelated and 9/10 matched related donors receive oral tacrolimus twice daily on days -1 to 180 followed by a taper; methotrexate IV on days 1, 3, 6, and 11; and oral mycophenolate mofetil twice daily on days -2 to 60 followed by a taper. All patients also receive antithymocyte globulin IV over 4 to 6 hours once a day on days -4 to -1. - Allogeneic stem cell transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. Patients receive filgrastim (G-CSF) beginning on day 7 and continuing until blood counts recover. - Lymphocyte infusion: Patients with progressive or stable disease while off immunosuppression and no active GVHD may receive up to 3 donor lymphocyte infusions from the original donor at 8-week intervals beginning on day 180 or 210 . Quality of life is assessed at baseline. After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for up to 3 years. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Trial information was received from ClinicalTrials.gov and was last updated in February 2017.
Information provided to ClinicalTrials.gov by Wake Forest University Health Sciences.