Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

Lymphoma Clinical Trial

Official title:

Hematopoietic Stem Cell Transplantation Using Bone Marrow Or Peripheral Blood Stem Cells From Matched, Unrelated, Volunteer Donors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00054327
• Other study ID #: CWRU1Y00
• Secondary ID: P30CA043703CASE-
• Status: Completed
• Phase: Phase 2
• First received: February 5, 2003
• Last updated: June 19, 2013
• Start date: November 2000
• Est. completion date: September 2011

Study information

• Verified date: June 2013
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 55 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Diseases
• Myeloproliferative Disorders
• Preleukemia

Intervention

Drug:
• busulfan
Given orally 1mg/kg/dose (or 40mg/m2/dose for young children)
• cyclophosphamide
Given IV
• cytarabine
Given IV

Radiation:
• radiation therapy
Patients undergo total body irradiation

Drug:
• Etoposide
infusion

Procedure:
• Stem Cell Transfusion

Locations

Country	Name	City	State
United States	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rates of Durable Engraftment	Number of days that patients take to reach engraftment defined as time to hematologic engraftment will be defined as ANC >500/µl and platelets >20K/µl without transfusion support.	at day 42	No
Secondary	Graft-versus-host Disease (GVHD)	Number of patients that develop acute graft-versus-host disease by grades 0-4. Grade O is no development of GVHD. Grade 1-4 is increase severity of skin, liver and gut involvement with 1 being least severe and 4 being most severe.	at 100 days post transplant	No
Secondary	Incidence of Recurrent Disease	Number of patients that have disease recurrence.	at day 100 post transplant	No
Secondary	Toxicity as Measured by CTC v2.0	Number of patients that experience grade 3 or above toxicity. See serious adverse event list for toxicities.	at 100 days post transplant	Yes