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

Case Comprehensive Cancer Center (Case CCC)

Status and phase: Completed; Phase 2

Conditions: Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Splenic Marginal Zone Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With T(15;17)(q22;q12); Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Childhood Myelodysplastic Syndromes; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Post-transplant Lymphoproliferative Disorder; Peripheral T-Cell Lymphoma; Adult Acute Myelomonocytic Leukemia (M4); Small Intestine Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Adult Acute Monocytic Leukemia (M5b); Childhood Chronic Myelogenous Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Recurrent Small Lymphocytic Lymphoma; Childhood Acute Monocytic Leukemia (M5b); Recurrent Grade 2 Follicular Lymphoma; Adult Acute Myeloid Leukemia With T(8;21)(q22;q22); Childhood Acute Monoblastic Leukemia (M5a); Accelerated Phase Chronic Myelogenous Leukemia; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Adult Acute Myeloid Leukemia With T(16;16)(p13;q22); Adult Acute Myeloblastic Leukemia With Maturation (M2); Recurrent Mycosis Fungoides/Sezary Syndrome; Hepatosplenic T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Acute Myelomonocytic Leukemia (M4); Childhood Acute Erythroleukemia (M6); Waldenstrom Macroglobulinemia; Recurrent Adult Hodgkin Lymphoma; Childhood Acute Promyelocytic Leukemia (M3); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Refractory Multiple Myeloma; Adult Pure Erythroid Leukemia (M6b); Recurrent Childhood Acute Lymphoblastic Leukemia; Previously Treated Myelodysplastic Syndromes; Anaplastic Large Cell Lymphoma; De Novo Myelodysplastic Syndromes; Relapsing Chronic Myelogenous Leukemia; Adult Acute Monoblastic Leukemia (M5a); Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Testicular Lymphoma; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Adult Acute Myeloblastic Leukemia Without Maturation (M1); Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Burkitt Lymphoma; Intraocular Lymphoma; Adult Acute Myeloid Leukemia With Del(5q); Adult Erythroleukemia (M6a); Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Diffuse Large Cell Lymphoma; Adult Acute Lymphoblastic Leukemia in Remission; Secondary Myelodysplastic Syndromes; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult T-cell Leukemia/Lymphoma; Childhood Acute Myeloblastic Leukemia With Maturation (M2)

Treatments: Procedure: allogeneic bone marrow transplantation; Drug: busulfan; Drug: methotrexate; Drug: cyclophosphamide; Drug: methylprednisolone; Drug: cyclosporine

Study type: Interventional

Funder types: Other

Identifiers

NCT01177371

NCI-2010-01793

CWRU1494T

Details and patient eligibility

About

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.

Full 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.

Enrollment: 13 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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13 participants in 1 patient group

Arm I

Experimental group

Description:

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.

Treatment:

Drug: cyclosporine

Drug: methylprednisolone

Drug: cyclophosphamide

Drug: methotrexate

Drug: busulfan

Procedure: allogeneic bone marrow transplantation