Transplantation of Unrelated Donor Hematopoietic Stem Cells for the Treatment of Hematological Malignancies
N/A
60 Years
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms, Unusual Cancers of Childhood
Trial Information
Transplantation of Unrelated Donor Hematopoietic Stem Cells for the Treatment of Hematological Malignancies
OBJECTIVES:
Primary
- Determine the effectiveness of unrelated donor allogeneic hematopoietic stem cells for
transplantation after conditioning for the treatment of patients with high-risk
hematologic malignancies.
- Compare survival, disease-free survival (DFS), response rate, and toxicity rates in
these patients with historical controls.
- Compare the rate and severity of acute and chronic GVHD after allogeneic hematopoietic
stem cell transplantation in patients with hematopoietic malignancies with historical
controls transplanted with stem cells from related sibling donors
- Assess engraftment, long-term hematopoietic recovery, relapse rate, and disease-free
survival when allogeneic hematopoietic stem cells are used as a source of stem cells
for transplantation in patients with high-risk hematological malignancies.
- Assess engraftment, long-term hematopoietic recovery, and overall survival when
allogeneic hematopoietic stem cells are used as a source of stem cells for
transplantation in patients who have graft failure or graft rejection.
- Compare engraftment, long-term hematopoietic recovery, rate of GVHD, rate of relapse,
toxicity rates, overall disease-free survival and overall survival when donor leukocyte
infusions (DLI) are given for patients who have disease recurrence, progression, or low
donor chimerisms after unrelated stem cell transplantation or before DLI with
historical controls of other donor leukocyte infusions.
Secondary
- Determine the quality of life of patients undergoing hematopoietic stem cell
transplantation or donor leukocyte infusions from unrelated HLA genotypically-identical
donors.
OUTLINE: Patients are assigned to 1 of 8 treatment groups.
- Group 1*: Patients undergo total body irradiation (TBI) twice a day on days -7 to -4.
Patients then receive cyclophosphamide IV over 1 hour on days -3 and -2. On day 0
patients undergo stem cell transplantation (SCT). Beginning on day 7, patients receive
filgrastim (G-CSF) IV once daily until blood counts recover.
- Group 2 (patients who have previously experienced dose-limiting radiotherapy): Patients
receive oral busulfan 4 times daily on days -7 to -4 and cyclophosphamide IV over 1
hour on days -3 and -2. On day 0 patients undergo SCT. Beginning on day 7, patients
receive G-CSF IV once daily until blood counts recover.
- Group 3 (pediatric patients only): Patients receive busulfan IV 4 times daily on days
-9 to -6 and cyclophosphamide IV over 1 hour and fludarabine IV over 30 minutes on days
-5 to -2. On day 0 patients undergo SCT. Beginning on day 7, patients may receive G-CSF
IV once daily until blood counts recover.
- Group 4 (second SCT for patients who have experienced graft rejection or failure)*:
Patients receive low-dose fludarabine IV over 30 minutes on days -4 to -2. Patients
then undergo low-dose TBI once followed by SCT on day 0. Beginning on day 7, patients
may receive G-CSF IV once daily until blood counts recover.
- Group 5 (patients who developed grade 3 cystitis after prior
cyclophosphamide-containing therapy): Patients receive carmustine IV over 2 hours on
day -6, etoposide IV over 2 hours and cytarabine IV over 30 minutes on days -5 to -2,
and melphalan IV over 30 minutes on day -1 (BEAM). On day 0, patients undergo SCT.
Beginning on day 7, patients receive G-CSF IV once daily until blood counts recover.
- Group 6 (cord blood transplantation): Patients receive anti-thymocyte globulin IV once
daily and methylprednisolone IV twice daily on days -3 to -1. On day 0, patients
undergo an umbilical cord blood SCT.
- Group 7 (patients with relapsing or progressive disease after prior transplants or low
donor chimerisms)*: Patients must not have existing graft-versus-host disease (GVHD).
Patients receive donor lymphocyte infusions with conditioning chemotherapy and/or
radiotherapy at the discretion of the investigator.
- Group 8 (pediatric patients only)*: Patients undergo TBI twice a day on days -7 to -5.
Patients also receive etoposide IV over 24 hours on day -4 and cyclophosphamide IV over
1 hour on days -3 and -2. On day 0, patients undergo SCT. Beginning on day 7, patients
may receive G-CSF IV once daily until blood counts recover.
NOTE: *Patients who have received > 3000 cGy to the central nervous system or > 2000 cGy to
the lung or liver may not receive any regimen containing total body irradiation (TBI)
All patients receive GVHD prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11;
cyclosporine and/or tacrolimus on days -2 to 100; and/or methylprednisolone IV on days 7 to
100.
Patients with an unrelated donor who experience a relapse prior to transplantation, may
proceed directly to transplantation. However, if immediate transplantation from the
unrelated donor is not possible, the patient must be re-induced into a complete
hematological remission. Patients who experience graft failure or graft rejection after
allogeneic transplantation are eligible for a second stem cell infusion from the original
donor.
Quality of life is assessed at baseline and at 7 days, 3 months, and 1 year after
transplantation.
After completion of study treatment, patients are followed periodically for survival.
PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following*:
- Acute lymphoblastic leukemia in any disease phase
- Patients with any of the following high-risk features are encouraged to
enroll:
- Philadelphia chromosome positive disease
- L3 morphology, especially in the presence of t(8;14), t(8;22), or
t(2;8)
- Patients not in remission at day 28 of first induction
- High LDH (i.e., ≥ 300 IU/mL at presentation)
- Pre-B-cell, mixed lineage, or Burkitt's markers
- Relapsed in the marrow while receiving continuous chemotherapy
- Within 6 months after stopping chemotherapy
- Relapse in one organ or extramedullary relapses in more than one organ
while still receiving chemotherapy
- Hodgkin's or non-Hodgkin's lymphoma beyond first complete remission (CR) or in
first CR with features of high-risk disease, including, but not limited to:
- Lymphoma not in CR after 3 courses of primary therapy
- Patients with bulky disease at presentation, especially bulky mediastinal
disease
- Patients with LDH ≥ 300 IU/mL at presentation
- Patients with extranodal disease
- Patients with first remission within less than 1 year
- Stage IV disease at presentation, especially with marrow involvement
- Patients with high-intermediate or high International Index Scores
- Acute myeloid leukemia (AML) meeting the following criteria:
- Beyond first remission or high-risk disease in first CR
- Required multiple courses of induction therapy to achieve a remission
- Had residual leukemia on day 14-28 bone marrow examination after initial
induction
- Patients with any cytogenetic abnormality except inv 16 or t(8;21)
- Chronic myelogenous leukemia in the chronic or early accelerated phase of the
disease
- Patients with blast crisis that can be induced back into chronic phase may
be transplanted in second chronic phase
- Myelodysplastic syndromes (MDS) meeting the following requirements:
- Transfusion-dependent refractory anemia (RA), RA with excess blasts (RAEB),
RAEB in transformation, or chronic myelomonocytic leukemia (CMML)
- Patients with MDS that present with or evolve to AML must be re-induced
back to remission prior to initiating a search for an unrelated donor NOTE:
*Patients with other hematologic malignancies not listed above, including
diseases such as chronic lymphocytic leukemia (CLL), multiple myeloma, or
rare pediatric malignancies, or patients who are felt to be at high-risk
for relapse but who do not have features listed, may be allowed at the
discretion of the investigator.
- Must have failed prior stem cell transplantation
- Must have a suitable unrelated allogeneic hematopoietic stem cell donor
- A 5/6 match degree is acceptable for unrelated bone marrow donors
- A 4/6 match degree is acceptable for unrelated cord blood units
PATIENT CHARACTERISTICS:
- SWOG performance status (PS) 0-2 OR
- Karnofsky PS 50-100% OR
- Lansky PS 50-100%
- Creatinine clearance ≥ 45 mL/min
- Creatinine ≤ 2.5 mg/dL
- Bilirubin ≤ 2 mg/dL (abnormally high liver function tests allowed if the only source
for the elevation is due to lymphoma of the liver)
- AST or ALT ≤ 2 times normal (abnormally high liver function tests allowed if the only
source for the elevation is due to lymphoma of the liver)
- No patients at high risk of veno-occlusive disease
- Not pregnant or nursing
- Negative serum pregnancy test
- Fertile patients must use an effective contraceptive method
- DLCO ≥ 50% of predicted
- FEV_1/FVC ≥ 65% of predicted
- No current congestive heart failure (CHF) and/or LVEF ≥ 45%
- No myocardial infarction within the past 6 months
- No unstable angina within the past 6 months
- HIV negative
- Life expectancy must not be limited by disease other than malignancy
- No allergy to any chemotherapeutic agent included in the regimen
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of Participants With Disease Free Survival (DFS).
Outcome Description:
Determine the effectiveness of unrelated donor allogeneic hematopoietic stem cells for transplantation after conditioning for the treatment of high-risk hematopoietic malignancies. Disease-free survival: The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer.
Outcome Time Frame:
Duration of the study; Up to 2 years
Safety Issue:
No
Principal Investigator
Richard Maziarz, MD
Investigator Role:
Study Chair
Investigator Affiliation:
OHSU Knight Cancer Institute
Authority:
United States: Institutional Review Board
Study ID:
CDR0000452794
NCT ID:
NCT00281879
Start Date:
February 2006
Completion Date:
March 2008
Related Keywords:
- Chronic Myeloproliferative Disorders
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- Unusual Cancers of Childhood
- adult acute lymphoblastic leukemia in remission
- L1 adult acute lymphoblastic leukemia
- L2 adult acute lymphoblastic leukemia
- L3 adult acute lymphoblastic leukemia
- recurrent adult acute lymphoblastic leukemia
- accelerated phase chronic myelogenous leukemia
- blastic phase chronic myelogenous leukemia
- chronic phase chronic myelogenous leukemia
- relapsing chronic myelogenous leukemia
- childhood acute lymphoblastic leukemia in remission
- L1 childhood acute lymphoblastic leukemia
- L2 childhood acute lymphoblastic leukemia
- L3 childhood acute lymphoblastic leukemia
- recurrent childhood acute lymphoblastic leukemia
- recurrent adult Hodgkin lymphoma
- recurrent/refractory childhood Hodgkin lymphoma
- stage IV adult Hodgkin lymphoma
- stage IV childhood Hodgkin lymphoma
- adult acute myeloid leukemia in remission
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- childhood acute myeloid leukemia in remission
- recurrent adult acute myeloid leukemia
- recurrent childhood acute myeloid leukemia
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- secondary acute myeloid leukemia
- refractory anemia with excess blasts in transformation
- refractory anemia with excess blasts
- refractory anemia
- chronic myelomonocytic leukemia
- childhood chronic myelogenous leukemia
- chronic eosinophilic leukemia
- primary myelofibrosis
- chronic neutrophilic leukemia
- de novo myelodysplastic syndromes
- atypical chronic myeloid leukemia, BCR-ABL negative
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- juvenile myelomonocytic leukemia
- nodal marginal zone B-cell lymphoma
- 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 immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent childhood large cell lymphoma
- recurrent childhood lymphoblastic lymphoma
- recurrent childhood small noncleaved 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 chronic lymphocytic leukemia
- refractory hairy cell leukemia
- refractory multiple myeloma
- splenic marginal zone lymphoma
- stage I multiple myeloma
- stage II multiple myeloma
- stage III adult Burkitt lymphoma
- stage III adult Hodgkin 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 immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage III chronic lymphocytic leukemia
- 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 multiple myeloma
- stage III small lymphocytic 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 chronic lymphocytic leukemia
- 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
- stage III childhood Hodgkin lymphoma
- stage III childhood large cell lymphoma
- stage III childhood lymphoblastic lymphoma
- stage III childhood small noncleaved cell lymphoma
- stage IV childhood large cell lymphoma
- stage IV childhood lymphoblastic lymphoma
- stage IV childhood small noncleaved cell lymphoma
- unusual cancers of childhood
- childhood myelodysplastic syndromes
- Neoplasms
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Lymphoma, Large-Cell, Immunoblastic
- Hematologic Neoplasms
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| OHSU Knight Cancer Institute | Portland, Oregon 97239 |
