Clinical trial NCT00054327: Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
Official title: Hematopoietic Stem Cell Transplantation Using Bone Marrow Or Peripheral Blood Stem Cells From Matched, Unrelated, Volunteer Donors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Keywords: adult acute myeloid leukemia in remission
childhood acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
adult acute lymphoblastic leukemia in remission
childhood acute lymphoblastic leukemia in remission
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 3 follicular lymphoma
secondary acute myeloid leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent mantle cell lymphoma
refractory anemia with ringed sideroblasts
refractory anemia
chronic myelomonocytic leukemia
refractory cytopenia with multilineage dysplasia
previously treated myelodysplastic syndromes
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
relapsing chronic myelogenous leukemia
childhood chronic myelogenous leukemia
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
juvenile myelomonocytic leukemia
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)
childhood myelodysplastic syndromes
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-02-06
Enrollment: 34
Sex: ALL
Maximum age (years): 55
Standard ages: CHILD
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 and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related donor, that do not exactly match the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This phase II trial is studying how well giving chemotherapy with or without radiation therapy followed by donor stem cell transplant works in treating patients with hematologic cancer.

Detailed description: OBJECTIVES:

* Determine a standard approach to hematopoietic stem cell transplantation with matched unrelated donors in patients with hematologic malignancies.
* Determine the toxicity of this regimen in these patients.
* Determine the relapse rate and survival rate in patients treated with this regimen.
* Correlate incidence and severity of graft-versus-host disease with relapse and survival in patients treated with this regimen.

OUTLINE: Patients receive 1 of the following preparative regimens:

* Regimen A: Patients receive cytarabine IV over 1 hour twice daily on days -9 to -7 and cyclophosphamide IV over 2 hours on days -6 and -5. Patients also undergo total body irradiation (TBI) twice daily on days -4 to -1.
* Regimen B-1: Patients receive cyclophosphamide IV and TBI as in regimen A.
* Regimen B-2: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4. Patients also undergo TBI twice daily on days -3 to -1.
* Regimen B-3: Patients receive TBI on days -7 to -5. Patients receive cyclophosphamide IV over on days -4 to -3.
* Regimen C: Patients receive oral busulfan 4 times daily on days -8 to -5 and cyclophosphamide IV over 2 hours on days -4 to -2.
* Regimen D: Patients receive TBI on days -6 to -4. Patients receive etoposide infusion on day -3.

All patients undergo stem cell transplantation from a matched, unrelated donor on day 0.

Patients are followed weekly for 100 days, at 6 months, and then every 6 months for 2.5 years.

PROJECTED ACCRUAL: 50

Eligibility criteria: Eligibility Criteria:

1. Patients with histologic confirmation of the following diseases are eligible:

   1. AML in first, second or greater remission
   2. AML in early relapse, defined at \<30% marrow blasts
   3. ALL in second or greater complete remission
   4. High risk ALL in first complete remission, with high risk being defined by the presence of t(4;11), t(9;22), or t(8;14) translocation, or patients presenting with extreme hyperleukocytosis (initial WBC \>500 K/ml) or failure to achieve a complete remission after standard induction therapy.
   5. CML
   6. Myelodysplastic syndromes (including evolution to AML, e.g., Refractory Anemia with Excess Blasts (RAEB), or Refractory Anemia with Excess Blasts in transformation (RAEB-t).
   7. Lymphoma (intermediate and high grade) chemosensitive (CR or PR) after first or greater relapse or chemosensitive to first line therapy but only achieving PR.
   8. Hematologic Disease and Inherited Immunodeficiencies
   9. Hodgkin's disease, relapsed or refractory to standard treatments.
2. Patients must be less than or equal to 55 years of age.
3. Patients (or guardians if minor) must be able to give informed consent. Children older than 11 years of age must assent to the process.
4. Patients or their guardians must demonstrate proof-of-payment.
5. Patients must have an ECOG Performance Status of 2 or less. (See Appendix I)
6. Patients must have no evidence of active infection at the time of transplantation.
7. Patients must be HIV nonreactive.
8. Patients must have a pre-transplant, multi-organ assessment prior to transplantation with the following outcome:

   1. resting ejection fraction of 50% or greater (or shortening fraction greater than 28% for small children).
   2. Diffusion capacity of 50% or greater of predicted, a FEV1 of 50% or greater, and a P2O of 80 mm Hg as demonstrated on pulmonary function testing.
   3. serum creatinine of less than or equal to 2.0 mg/dL and/or a corrected creatinine clearance of 50 ml/min or greater on 24 hr urine.
   4. A total bilirubin of less than 2.5 mg/dL and an AST less than 4 times the upper limits of normal.
9. Females who are childbearing age may not be pregnant or lactating and must have a current negative pregnancy test

Ineligibility Criteria:

* Patients who have a life expectancy of less than three months with therapy.
* Patients who have an ECOG performance status greater than 2, (See Appendix I) or Lansky Scale \< 70%.
* Patients who have angina and/or congestive heart failure requiring treatment, or who have had a myocardial infarction within the past year.
* Patients who have a resting ejection of less than 50% (or shortening fraction less than 28%) and who have not been cleared for transplant by cardiology
* Patients who have severe renal disease as demonstrated by a serum creatinine greater than 2.0 mg/dL and/or a corrected creatinine clearance less than 50 ml/min. (corrected for BSA of 1.73 m¬2)
* Patients who have had any complication that makes the risk of death during transplantation from non-malignant causes greater than the risk of relapse.
* Patients who have any active infection such as a soft tissue infection, sinus infection, dental infection, fungal infection or hepatitis including chronic active hepatitis; if the infection is successfully treated, the patient may be reconsidered for transplantation at a later date.
* Patients who have decreased pulmonary function due to any disorder as demonstrated by a diffusion capacity of less than 50% of predicted, a FEV1 of less than 50% of predicted or a PO2 of less than 80 mm Hg pulmonary function testing.
* Patients who have decreased liver function as demonstrated by a total bilirubin of greater than 2.5 mg/dL and/or an AST greater than 4 times the upper limits of normal.
* Patients who have diabetes mellitus will be considered on a case-by-case basis. However, patients with diabetes who are not controlled by medical management will be ineligible.

-Patients who have a significant psychiatric illness will be considered on a case- by-case basis. With the patient's consent, their Mental Health Care worker will assist the managing transplant physicians in determining if the patient can safely undergo transplantation and comply with followup recommendations.

* Psychosocial assessment by the bone marrow transplant team may identify individuals for whom this form of therapy may be contraindicated. This decision will be based upon estimated adequacy of patient support systems and prediction of patient's compliance with medications, required diagnostic procedures and/or follow-up care.
* Females who are childbearing age may not be pregnant or lactating and must have a current negative pregnancy test
* Patients who had a stem cell transplant less than one year earlier

Primary outcomes:
measure: Rates of Durable Engraftment
timeFrame: at day 42
Secondary outcomes:
measure: Graft-versus-host Disease (GVHD)
timeFrame: at 100 days post transplant
measure: Incidence of Recurrent Disease
timeFrame: at day 100 post transplant
measure: Toxicity as Measured by CTC v2.0
timeFrame: at 100 days post transplant
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
name: Kenneth Cooke, MD
role: PRINCIPAL_INVESTIGATOR
References: