Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Cancer

• Status: Terminated
• Trial end date: 2012-03-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a monoclonal antibody, such as alemtuzumab, before transplant and tacrolimus and methotrexate after transplant may stop this from happening.

PURPOSE: This phase II trial is studying the side effects of donor stem cell transplant and to see how well it works in treating patients with high-risk hematologic cancer.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Northside Hospital, Inc.
• Collaborator: Blood and Marrow Transplant Group of Georgia
• Treatments: Alemtuzumab; Busulfan; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Methotrexate; Rituximab; Tacrolimus

Criteria

• Diagnosis of one of the following hematological malignancies:

• CML, with 1 of the following:

• In first CP AND failed imatinib mesylate therapy, defined as failure to obtain a hematologic remission at 3 months or a major cytogenetic response (i.e., Ph+ cells < 35%) at 6 months or demonstrated clonal evolution or disease progression during therapy

• In accelerated phase with < 15% blasts

• In blast crisis that has entered into a second CP following induction chemotherapy

• AML, with 1 of the following:

• In second or subsequent complete remission (CR) (i.e., < 5% blasts by morphology, no residual leukemia by flow cytometry, and absence of cytogenetic abnormalities)

• Failed primary induction chemotherapy, but subsequently entered into a CR with ≤ 2 subsequent re-induction chemotherapy treatment(s)

• In first CR with intermediate-risk or poor-risk cytogenetics

• ALL with 1 of the following:

• In second or subsequent CR

• In first CR AND presence of t(9;22)

• MDS, with the following:

• High-risk disease, defined by IPSS score of ≥ 1.5 at diagnosis AND meets 1 of the following criteria:

• ≤ 10% blasts at diagnosis

• In morphologic CR (< 5% blasts) following cytoreductive chemotherapy

• CMML, with 1 of the following:

• ≤ 10% blasts at diagnosis

• In morphologic CR (< 5% blasts) following cytoreductive chemotherapy

• CLL/PLL with the following:

• Rai stage I-IV disease

• Failed ≥ 1 prior chemotherapy regimen (including fludarabine phosphate) or ASCT

• Documented chemosensitive or stable, non-bulky disease prior to transplant, defined as < 20% bone marrow involvement AND lymph node size < 3 cm in axial diameter

• No bulky tumor masses, elevated lactate dehydrogenase (LDH), B symptoms, or progressive disease prior to transplant

• Low-grade non-Hodgkin lymphoma (NHL) (i.e., small lymphocytic lymphoma, follicular center lymphoma [grade 1 or 2], marginal zone lymphoma, or B-cell lymphoma), with the following criteria:

• Failed ≥ 1 prior chemotherapy regimen or ASCT

• Documented chemosensitive or stable, non-bulky disease prior to transplant, defined as < 20% bone marrow involvement AND lymph node size < 3 cm in axial diameter

• Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and involved-field radiotherapy are not considered a prior regimen)

• No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant

• Mantle cell lymphoma, with the following:

• Failed to achieve remission or recurred after either conventional chemotherapy or ASCT

• Responsive or stable disease to most recent prior therapy

• No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant

• Intermediate-grade NHL (i.e., follicular center lymphoma [grade 3] or diffuse large cell lymphoma), meeting the following criteria:

• Failed to achieve remission or recurred after either conventional chemotherapy or ASCT

• Documented chemosensitive, non-bulky disease prior to transplant, defined as at least a partial remission to salvage chemotherapy (≥ 50% reduction in diameter of all disease sites)

• No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant

• Hodgkin lymphoma, with the following:

• Relapsed after prior ASCT OR after ≥ 2 combination chemotherapy regimens and ineligible for ASCT

• Documented chemosensitive, non-bulky disease prior to transplant, defined as at least a partial remission to salvage chemotherapy (≥ 50% reduction in diameter of all disease sites)

• No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant

• Peripheral T-cell NHL, with the following:

• Failed to achieve remission or recurred after either conventional chemotherapy or ASCT

• Documented chemosensitive, non-bulky disease prior to transplant, defined as at least a partial remission to salvage chemotherapy (≥ 50% reduction in diameter of all disease sites)

• No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant

• Myeloproliferative syndrome with poor risk features, meeting 1 of the following criteria:

• < 55 years old AND Lille score of 1

• Lille score of 2

• HgB < 10 g/dL AND abnormal karyotype

• High-risk disease, with 1 of the following:

• Age 40-72 years

• Any age AND deemed to be at significantly increased risk of morbidity and death following a standard, myeloablative unrelated donor stem cell transplant (e.g., received extensive prior therapy, including ASCT)

• HLA-matched unrelated donor available, with 1 of the following:

• 8/8 match at HLA-A, B, C, or DR loci by high-resolution genotyping

• Single allelic mismatch at either the HLA-B or HLA-C loci donor by high-resolution molecular typing

• No single allelic mismatch at HLA-A or HLA-DR loci

• KPS 80-100%

• Adapted weighted Charlson Comorbidity Index < 3

• Serum creatinine ≤ 2.0 mg/dL

• AST or ALT < 3 times upper limit of normal (ULN)

• Total bilirubin < 1.5 times ULN

• LVEF ≥ 45%

• DLCO > 50%

• No hypoxia at rest with oxygen saturation < 92% on room air (corrected with bronchodilator therapy)

• No other severe pulmonary function abnormalities

• No HIV infection

• No active hepatitis B or C infection that, in the opinion of a gastroenterologist or the transplant committee, places the patient at moderate to high risk for developing severe hepatic disease

• No active opportunistic infection (e.g., fungal pneumonia, tuberculosis, or viral infection)