Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other Disorders

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00544115
• Other study ID #: 01089
• Secondary ID: P30CA033572CHNMC
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 16, 2001
• Est. completion date: December 30, 2024

Study information

• Verified date: March 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• 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 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 260
• Est. completion date: December 30, 2024
• Est. primary completion date: March 13, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Graft Versus Host Disease
• Graft vs Host Disease
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Diseases
• Myeloproliferative Disorders
• Neoplasms, Plasma Cell
• Plasmacytoma
• Precancerous Conditions
• Precancerous/Nonmalignant Condition
• Preleukemia
• Syndrome

Intervention

Drug:
• busulfan

• cyclophosphamide

• cyclosporine

• etoposide

• fludarabine phosphate

• melphalan

• methotrexate

• mycophenolate mofetil

• sirolimus

• tacrolimus

Procedure:
• allogeneic hematopoietic stem cell transplantation

• peripheral blood stem cell transplantation

Radiation:
• total-body irradiation

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neutrophil Engraftment - The Days Till ANC Recovery	The primary engraftment endpoint, neutrophil engraftment, is defined as the first of three consecutive days on which the absolute neutrophil count is > 500/µL. The duration and extent of neutrophil engraftment is the time from transplant to neutrophil engraftment.	Up to 180 days post transplant
Secondary	Two-year Overall Survival	Overall survival (OS) was measured from peripheral stem cell infusion to death from any cause. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula. Participants were followed up to 2 years after transplant and Kaplan-Meier survival analysis was used to generate the two-year Overall Survival estimate presented.	Up to 2 years post transplant