High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

Recurrent Mantle Cell Lymphoma Clinical Trial

Official title:

High-dose Busulfan, High-dose Cyclophosphamide, and Allogeneic Bone Marrow Transplantation for Leukemia, Myelodysplastic Syndromes, Multiple Myeloma and Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01177371
• Other study ID #: CWRU1494T
• Secondary ID: NCI-2010-01793
• Status: Completed
• Phase: Phase 2
• First received: August 5, 2010
• Last updated: August 5, 2010
• Start date: March 1988
• Est. completion date: February 2010

Study information

• Verified date: August 2010
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Giving high doses of chemotherapy drugs, such as busulfan and cyclophosphamide, before a donor bone marrow transplant helps stop the growth of cancer cells. It may also 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 cyclosporine, methylprednisolone, and methotrexate after transplant may stop this from happening.

PURPOSE: This clinical trial studies high-dose busulfan and high-dose cyclophosphamide followed by donor bone marrow transplant in treating patients with leukemia, myelodysplastic syndrome, multiple myeloma, or recurrent Hodgkin or Non-Hodgkin lymphoma.

Description:

OBJECTIVES:

I. To determine the toxicity and efficacy of the high-dose chemotherapy regimen which employs busulfan, cyclophosphamide, and allogeneic bone marrow transplantation.

II. To ascertain feasibility (safety) and efficacy of the use of intensive chemotherapy regimen (busulfan and cyclophosphamide) followed by allogeneic bone marrow transplantation in patients with leukemia, myelodysplastic syndromes, multiple myeloma, and lymphoma.

OUTLINE:

HIGH-DOSE CHEMOTHERAPY: Patients receive oral busulfan every 6 hours on days -8 to -5 and cyclophosphamide IV over 2 hours on days -4 and -3, or -4 to -2 .

TRANSPLANTATION: Patients undergo allogeneic bone marrow transplant IV over 2-3 hours on day 0.

GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine IV over 6 hours on day -1, over 10 hours twice daily on days 0-20, and then orally every 12 hours beginning on day 21 and continuing for 12 months with taper at 9 months. Patients also receive methylprednisolone IV or orally beginning on day 8 and continuing for 7 months with taper at 4 months. Some patients may also receive methotrexate IV on days 1, 3 and 6 .

After completion of study treatment, patients are followed up periodically.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: February 2010
• Est. primary completion date: February 2000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Criteria

• Acute non-lymphocytic leukemia (FAB types M1-M7) in first, or second remission, or early first or second bone or marrow relapse (>31% marrow blasts and no circulating peripheral blasts)

• All patients with acute promyelocytic leukemia in first complete remission who have received retinoic acid and chemotherapy are not eligible

• Acute lymphocytic leukemia in first or second remission, or early first or second bone marrow relapse (31% marrow blasts and no circulating peripheral blasts)

• Pediatric ALL patients in first complete remission are not eligible

• Chronic myelogenous leukemia in first or second chronic phase, or accelerated phase

• Myelodysplastic syndrome =< 50 years

• Lymphoma patients age =< 50 years (non Hodgkins or Hodgkins) in first or second relapse, or refractory disease, who are ineligible for autologous bone marrow transplantation because of tumor in the bone marrow

• Multiple myeloma patients age =< 50 who have relapsed or are refractory to at least 2 chemo-radiation or chemotherapy regimens

• Patients who have failed a previous allogeneic bone marrow transplant

• Patients with inborn errors of metabolism

• ECOG performance status of 0 or 1

• Karnofsky performance status of >= 70%

• Patients must be HTLV-III (HIV) anti-body negative

• Acute and chronic leukemia patients must be age =< 50 years; patients up to age 60 years for any of these diseases who have a syngeneic donor are eligible

• Patients (or bone marrow donors) who are HTLV-III (HIV) antibody positive are ineligible for this study

• Patients must not have active infection

• Patients must not have cytotoxic chemotherapeutic agents for at least 4 weeks before the transplant conditioning regimen is to begin

• It is recommended but not required that acute leukemia patients undergoing transplantation in first remission must have received at least one course of consolidation therapy

• Patients undergoing transplant in early relapse are eligible for transplant in first and second relapse only

• Patients must have no history of acute myocardial infarction in the 6 months prior to transplantation, angina pectoris requiring nitrate therapy, uncontrolled major ventricular dysrhythmia, uncontrolled hypertension, or uncontrolled congestive heart failure

• A gated-pool radionuclide scan fraction must be >= 50%

• Serum creatinine must be =< 1.8% and a 24 hour creatinine clearance must be >= 60ml/min

• Serum direct bilirubin >= 1.8mg%, or serum SGOT or SGPT > twice normal will exclude patients from this study

• Severe symptomatic CNS disease of any etiology other than CNS leukemia will exclude patients from study

• FEV1 and DLco (corrected) must be >= 60% of normal

• pO2 > 60mmHg

• Insulin-dependent diabetes mellitus or uncompensated major thyroid or adrenal dysfunction render patients ineligible

• Written informed consent must be obtained

• Patients treated previously with radiation therapy in excess of 1000 cGy (rads) to any thoracic or abdominal port, or in excess of 3000 cGy (rads) to cranial-spinal ports, who are not eligible for other protocols are eligible for this study

• DONOR: All genotypically HLA- or D/DR identical siblings are eligible to be bone marrow donors so long as their general medical condition permits the safe use of general or spinal anesthesia; selected donors who are not HLA-identical may be considered for use as long as they are D/DR identical, MLC compatible, and are in good condition to safely undergo spinal or general anesthesia

• DONOR: This protocol will allow the use of donors who are unrelated but are HLA-A, b, C, D/Dr identical and MLC (mixed lymphocyte culture) compatible

• Patient must have adequate insurance to cover the cost of the transplant and hospitalization

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Accelerated Phase Chronic Myelogenous Leukemia
• Adult Acute Lymphoblastic Leukemia in Remission
• Adult Acute Megakaryoblastic Leukemia (M7)
• Adult Acute Monoblastic Leukemia (M5a)
• Adult Acute Monocytic Leukemia (M5b)
• Adult Acute Myeloblastic Leukemia With Maturation (M2)
• Adult Acute Myeloblastic Leukemia Without Maturation (M1)
• Adult Acute Myeloid Leukemia in Remission
• Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
• Adult Acute Myeloid Leukemia With Del(5q)
• Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
• Adult Acute Myeloid Leukemia With T(15;17)(q22;q12)
• Adult Acute Myeloid Leukemia With T(16;16)(p13;q22)
• Adult Acute Myeloid Leukemia With T(8;21)(q22;q22)
• Adult Acute Myelomonocytic Leukemia (M4)
• Adult Acute Promyelocytic Leukemia (M3)
• Adult Erythroleukemia (M6a)
• Adult Nasal Type Extranodal NK/T-cell Lymphoma
• Adult Pure Erythroid Leukemia (M6b)
• Anaplastic Large Cell Lymphoma
• Angioimmunoblastic T-cell Lymphoma
• Burkitt Lymphoma
• Childhood Acute Erythroleukemia (M6)
• Childhood Acute Lymphoblastic Leukemia in Remission
• Childhood Acute Megakaryocytic Leukemia (M7)
• Childhood Acute Monoblastic Leukemia (M5a)
• Childhood Acute Monocytic Leukemia (M5b)
• Childhood Acute Myeloblastic Leukemia With Maturation (M2)
• Childhood Acute Myeloblastic Leukemia Without Maturation (M1)
• Childhood Acute Myeloid Leukemia in Remission
• Childhood Acute Myelomonocytic Leukemia (M4)
• Childhood Acute Promyelocytic Leukemia (M3)
• Childhood Chronic Myelogenous Leukemia
• Childhood Myelodysplastic Syndromes
• Chronic Phase Chronic Myelogenous Leukemia
• Cutaneous B-cell Non-Hodgkin Lymphoma
• De Novo Myelodysplastic Syndromes
• Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
• Hepatosplenic T-cell Lymphoma
• Hodgkin Disease
• Intraocular Lymphoma
• Leukemia
• Leukemia, Erythroblastic, Acute
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Megakaryoblastic, Acute
• Leukemia, Monocytic, Acute
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myeloid, Chronic-Phase
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Promyelocytic, Acute
• Leukemia, T-Cell
• Leukemia-Lymphoma, Adult T-Cell
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Extranodal NK-T-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, Large-Cell, Immunoblastic
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Lymphoma, T-Cell, Peripheral
• Lymphomatoid Granulomatosis
• Lymphoproliferative Disorders
• Multiple Myeloma
• Mycosis Fungoides
• Myelodysplastic Syndromes
• Neoplasms, Plasma Cell
• Nodal Marginal Zone B-cell Lymphoma
• Peripheral T-Cell Lymphoma
• Post-transplant Lymphoproliferative Disorder
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• Previously Treated Myelodysplastic Syndromes
• Recurrent Adult Acute Lymphoblastic Leukemia
• Recurrent Adult Acute Myeloid Leukemia
• 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 Grade III Lymphomatoid Granulomatosis
• Recurrent Adult Hodgkin Lymphoma
• Recurrent Adult Immunoblastic Large Cell Lymphoma
• Recurrent Adult Lymphoblastic Lymphoma
• Recurrent Adult Non-Hodgkin Lymphoma
• Recurrent Adult T-cell Leukemia/Lymphoma
• Recurrent Childhood Acute Lymphoblastic Leukemia
• Recurrent Childhood Acute Myeloid Leukemia
• Recurrent Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome
• Recurrent Small Lymphocytic Lymphoma
• Refractory Multiple Myeloma
• Relapsing Chronic Myelogenous Leukemia
• Secondary Myelodysplastic Syndromes
• Sezary Syndrome
• Small Intestine Lymphoma
• Splenic Marginal Zone Lymphoma
• Syndrome
• Testicular Lymphoma
• Waldenstrom Macroglobulinemia

Intervention

Drug:
• busulfan
Given orally
• cyclophosphamide
Given IV

Procedure:
• allogeneic bone marrow transplantation
Patients undergo allogeneic bone marrow transplant IV over 2-3 hours on day 0.

Drug:
• methylprednisolone
Given IV or orally
• methotrexate
Given IV
• cyclosporine
Given IV or orally

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate	no evidence of leukemia as judged by two peripheral blood smears and two bone marrow aspirates and biopsies. Disease-free and overall survival data will be computed from the day of marrow infusion.	obtained at least one month apart beginning no earlier than two month after marrow infusion	No
Primary	Toxicity as assessed by NCI CTC and engraftment (bone marrow) toxicity criteria		twice weekly	Yes