Allogeneic Bone Marrow Transplantation With Matched Unrelated Donors for Patients With Hematologic Malignancies

Allogeneic Bone Marrow Transplantation With Matched Unrelated Donors for Patients With Hematologic Malignancies Using a Preparative Regimen of Busulfan, Cyclophosphamide, and Fludarabine

Patients who have cancer of the bone marrow (leukemia) or lymph gland (lymphomas) are being asked to take part in this study. This study uses a new chemotherapy regimen and matched volunteer stem cell transplant to treat patients with cancers of this kind.

Study Overview

• Status: Completed
• Conditions: Hematologic Malignancies
• Intervention / Treatment: Drug: Busulfan, Cyclophosphamide and Fludarabine

Detailed Description

Patients who have cancer of the bone marrow (leukemia) or lymph gland (lymphomas) are being asked to take part in this study. This study uses a new chemotherapy regimen and matched volunteer stem cell transplant to treat patients with cancers of this kind.

High dose chemotherapy, followed by a transplant of stem cells collected from either bone marrow (BMT) or peripheral blood of an HLA (tissue type) matched unrelated donor, offers a potential cure for several serious blood diseases including acute and chronic leukemia, myelodysplastic syndrome and lymphoma.

However, the success of allogeneic (unrelated volunteer matched donor) transplant is limited by treatment related illness, death, and relapse in patients with refractory (resistant) disease and/or advanced age (older than 40 years).

Patients being sought for this study do not have an HLA-matched relative to donate stem cell; however, through The National Marrow Donor Program or International Registries, an HLA-matched unrelated donor has been found to donate stem cells. Preliminary data shows that the outcome is comparable between bone marrow and peripheral blood stem cell transplantations, and donor preference will determine which type of cells the patient receives.

To carry out an unrelated transplant, a normal person with similar HLA type must be available to donate cells. The patient must be prepared to accept the donor cells by decreasing the body's immune systems. In addition, the malignant (cancerous) cells must be destroyed to allow growth and repopulation of healthy donor cells. This is usually done by giving total body irradiation and chemotherapy, which is associated with severe side effects in patients over age 40.

In other studies, it has been found that treating the patient with two anticancer drugs, Busulfan and Cyclophosphamide, without total body irradiation, is safe and sufficiently immunosuppressive. High dose Busulfan and Cyclophosphamide are frequently used in combination prior to matched related bone marrow transplant in case of acute leukemia, myelodysplastic syndrome (MDS), Hodgkin's disease (HD), and chronic myeloid leukemia (CML). Fludarabine (another anticancer drug) suppresses the immune system and has strong anticancer effect against chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). Researchers are studying a new chemotherapy regimen that includes fludarabine, along with busulfan and cyclophosphamide, to provide more immunosuppression and anti-cancer effect without increasing the chemotherapy related toxicity in patients with CML, acute leukemia and MDS, CLL, NHL, and HD.

The purposes of this study are: 1) to decrease the side effects due to the chemotherapy used to treat the bone marrow; and 2) to increase the number of tumor cells killed. There will be up to 55 patients enrolled in this study at Emory University. The expected duration of each subject's participation in this study will be for two years.

• Study Type: Interventional
• Enrollment (Anticipated): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Universtiy Winship Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients eligible to participate in this study must have CML in the first chronic phase, AML in the first complete remission, AML in second remission, ALL or hybrid leukemia in the first complete remission, ALL in second remission, or advanced MDS. Final eligibility for this study will be determined by the health professionals conducting the trial.

Exclusion Criteria:

• Patients with active CNS malignant disease, or an invasive/systemic fungal infection are not eligible to participate in this study. Patients who are lactating, or who have an HLA identical or 1 antigen mismatched relative who is eligible and willing to donate bone marrow will also be excluded from the study. Final eligibility for this study will be determined by the health professionals conducting the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1; Chemotherapy-only conditioning regimen comprising busulfan (Bu), cyclophosphamide (Cy) and fludarabine (FLUDARA) followed by an allogeneic stem cell transplant.	Drug: Busulfan, Cyclophosphamide and Fludarabine; Bulsufan 1mg/kg/dose P.O. every 6 hours for 4 days. If intravenous, busulfan dose will be 0.8 mg/kg every 6 hours for 16 doses.; Fludarabine 40 mg/m2 a day for 5 days via IV over 2 hours, dose based on weight.; Cyclophosphamide given via IV over 1 hour at dose of 60 mg/kg/day for 2 consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assess activity of preparative regimen in patients with CML, AML, RAEB, RAEB-t, CLL, NHL, HD, in all patients with refractory anemia, ringed sideroblasts, undergoing allogeneic stem cell transplantation from volunteer matched unrelated donor (VUD).	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine disease-free and overall survival.	2 years+

Collaborators and Investigators

• Sponsor: Emory University

Study record dates

Study Major Dates

• Study Start: July 1, 1998
• Primary Completion (ACTUAL): October 1, 2007
• Study Completion (ACTUAL): October 1, 2007

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (ESTIMATE): September 21, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): April 6, 2012
• Last Update Submitted That Met QC Criteria: April 5, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Hematologic Malignancies
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine; Busulfan
• Other Study ID Numbers: 0709-1997