Clinical trial NCT00818961
Conditions: Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases
Keywords: accelerated phase chronic myelogenous leukemia adult acute lymphoblastic leukemia in remission adult acute myeloid leukemia in remission adult AML with 11q23 (MLL) abnormalities blastic phase chronic myelogenous leukemia chronic myelomonocytic leukemia chronic phase chronic myelogenous leukemia prolymphocytic leukemia recurrent adult T-cell leukemia/lymphoma refractory chronic lymphocytic leukemia relapsing chronic myelogenous leukemia secondary acute myeloid leukemia stage I adult T-cell leukemia/lymphoma stage I chronic lymphocytic leukemia stage II adult T-cell leukemia/lymphoma stage II chronic lymphocytic leukemia stage III adult T-cell leukemia/lymphoma stage III chronic lymphocytic leukemia stage IV adult T-cell leukemia/lymphoma stage IV chronic lymphocytic leukemia recurrent adult Hodgkin lymphoma anaplastic large cell lymphoma angioimmunoblastic T-cell lymphoma cutaneous B-cell non-Hodgkin lymphoma recurrent cutaneous T-cell NHL stage I cutaneous T-cell NHL stage II cutaneous T-cell NHL stage III cutaneous T-cell NHL stage IV cutaneous T-cell NHL extranodal marginal zone B-cell lymphoma of mucosal tissue nodal marginal zone B-cell lymphoma splenic marginal zone lymphoma contiguous st II adult diffuse large cell lymphoma contiguous st II adult diffuse mixed cell lymphoma contiguous st II adult diffuse sm cleaved cell lymphoma contiguous st II grade 1 follicular lymphoma contiguous st II grade 2 follicular lymphoma contiguous st II grade 3 follicular lymphoma contiguous st II mantle cell lymphoma contiguous st II marginal zone lymphoma contiguous st II small lymphocytic lymphoma stage I adult diffuse large cell lymphoma stage I adult diffuse mixed cell lymphoma stage I adult diffuse small cleaved cell lymphoma stage I grade 1 follicular lymphoma stage I grade 2 follicular lymphoma stage I grade 3 follicular lymphoma stage I mantle cell lymphoma stage I marginal zone lymphoma stage I small lymphocytic lymphoma noncontiguous st II adult diffuse large cell lymphoma noncontiguous st II adult diffuse mixed cell lymphoma noncontiguous st II adult diffuse sm cleaved cell lymphoma noncontiguous st II grade 1 follicular lymphoma noncontiguous st II grade 2 follicular lymphoma noncontiguous st II grade 3 follicular lymphoma noncontiguous st II mantle cell lymphoma noncontiguous st II marginal zone lymphoma noncontiguous st II small lymphocytic lymphoma stage III adult diffuse large cell lymphoma stage III adult diffuse mixed cell lymphoma stage III adult diffuse small cleaved cell lymphoma stage III grade 1 follicular lymphoma stage III grade 2 follicular lymphoma stage III grade 3 follicular lymphoma stage III mantle cell lymphoma stage III marginal zone lymphoma stage III small lymphocytic lymphoma stage IV adult diffuse large cell lymphoma stage IV adult diffuse mixed cell lymphoma stage IV adult diffuse small cleaved cell lymphoma stage IV grade 1 follicular lymphoma stage IV grade 2 follicular lymphoma stage IV grade 3 follicular lymphoma stage IV mantle cell lymphoma stage IV marginal zone lymphoma stage IV small lymphocytic lymphoma recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult gr III lymphomatoid granulomatosis recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent mantle cell lymphoma recurrent marginal zone lymphoma recurrent small lymphocytic lymphoma de novo MDS previously treated MDS secondary myelodysplastic syndromes Waldenstrom macroglobulinemia myelodysplastic/myeloproliferative disease
Sponsor: Northside Hospital, Inc.
Start date: 2005-05-01; Completion date: 2012-03-01
Enrollment: 36 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Detailed description:
OBJECTIVES:

* To evaluate the safety and toxicity of a reduced-intensity conditioning regimen followed by allogeneic bone marrow or peripheral blood stem cell transplantation from an HLA-matched unrelated donor in patients with high-risk hematologic malignancies.
* To evaluate engraftment by peripheral blood chimerism analysis.
* To determine the incidence and severity of acute and chronic graft-versus-host disease following the transplant.
* To examine the possibility of controlling hematologic malignancies by induction of a graft-versus-leukemia/tumor effect.
* To determine the disease-free survival, relapse, transplant-related mortality, and death from all causes.

OUTLINE:

* Reduced-intensity conditioning regimen: Patients receive 1 of 2 conditioning regimens according to diagnosis.

  * Regimen 1 (acute leukemia, myelodysplastic syndromes, myeloproliferative syndrome, or chronic myelogenous leukemia): Patients receive fludarabine phosphate IV over 30 minutes and busulfan IV over 3 hours on days -6 to -3 or orally 4 times daily on days -7 to -3.
  * Regimen 2 (lymphoproliferative malignancies): Patients receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 1 hour on days -5 to -3. Patients with CD20+ malignancies also receive rituximab IV over 4-6 hours on days -13, -6, 1, and 8.
* Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
* Graft-versus-host disease (GVHD) prophylaxis: Patients receive low-dose alemtuzumab subcutaneously on days -11 to -9 and tacrolimus IV over 24 hours beginning on day -3 and then orally twice daily beginning on day 14 and continuing until day 60, followed by a taper until day 180 in the absence of clinically significant GVHD. Patients also receive methotrexate on days 1, 3, and 6.

Patients who exhibit persistent mixed chimerism or disease relapse/progression despite full withdrawal of immunosuppression may receive up to 3 donor lymphocyte infusions.

Blood samples are taken on days 30, 60, and 100 and then every 4 weeks thereafter for chimerism studies by PCR analysis.

After completion of study therapy, patients are followed periodically for up to 60 months.

Arms: arm 1: All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on donor type
Interventions: intervention 1: alemtuzumab intervention 2: graft-versus-tumor induction therapy intervention 3: rituximab intervention 4: busulfan intervention 5: cyclophosphamide intervention 6: fludarabine phosphate intervention 7: methotrexate intervention 8: tacrolimus intervention 9: allogeneic bone marrow transplantation
Intervention descriptions: intervention 1: 43 mg subcutaneously over 3 days (3 mg on day -11, 10 mg on day -10, 30 mg on day -9) intervention 2: curative potential of allogeneic transplant results from the immune anti-tumor effect of donor cells or GVT/GVL intervention 3: in patients with Cd20+ malignancies: rituximab 375 mg/m\*2 day -13. rituximab 1000 mg/m\*2 on days, -6, +1, +8. intervention 4: For patients with AML, CML, MDS, MPS and ALL only: IV or oral busulfan may be given IV busulfan: 130 mg/m2 over 3 hours once daily on days -6, -5, -4 and -3 Oral busulfan: taken every 6 hours x 15 doses beginning on day -7 at 6pm and continuing through day -3 at 6am. 1 mg/kg test dose will be given prior to day -7 and PK samples will be drawn to calculate AUC. intervention 5: 750 mg/m2 infused over 1 hour once daily on days -5, -4 and -3. Cyclophosphamide will be started approximately 4 hours after the start of Fludarabine intervention 6: For patients with CLL, NHL \& HD: 30 mg/m2 infused over 30 minutes once daily on days -5, -4 and -3 For patients with AML, CML, MDS, MPS and ALL: 40 mg/m2 infused over 30 minutes once daily on days -6, -5, -4 and -3. intervention 7: 5 mg/m2 administered on days +1, +3 and +6 intervention 8: 0.03mg/kg/day infused over 24 hours starting on day -1 and switched to oral (twice daily divided dose) on day 14 or when able to tolerate PO intervention 9: Recipients will receive an allogeneic transplant on day 0 after receiving high-dose chemotherapy. This trial uses matched unrelated donor stem cells.

Protocol documents: