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Donor Stem Cell Transplant in Treating Older or Frail Patients With Hematologic Cancer

Primary Purpose

Chronic Myeloproliferative Disorders, Leukemia, Lymphoma

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
anti-thymocyte globulin
filgrastim
therapeutic allogeneic lymphocytes
busulfan
fludarabine phosphate
methotrexate
tacrolimus
nonmyeloablative allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, stage III adult diffuse small cleaved cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, noncontiguous stage II marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, noncontiguous stage II adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage IV adult diffuse mixed cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, noncontiguous stage II mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, stage II multiple myeloma, stage III multiple myeloma, chronic phase chronic myelogenous leukemia, primary myelofibrosis, polycythemia vera, prolymphocytic leukemia, stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, chronic myelomonocytic leukemia, adult acute myeloid leukemia in remission, secondary acute myeloid leukemia, Waldenström macroglobulinemia, essential thrombocythemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, 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), noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, stage I multiple myeloma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of a high-risk indolent hematologic malignancy meeting the following criteria: Chronic lymphocytic leukemia (CLL) meeting 1 of the following criteria: In second or subsequent remission Failed to achieve a complete remission (CR) after chemotherapy Non-Hodgkin's lymphoma (NHL) meeting 1 of the following criteria: Low-grade NHL meeting 1 of the following criteria: Standard-risk disease in second or subsequent remission Standard-risk disease and failed to achieve a CR after chemotherapy In first or subsequent remission with adverse International Prognostic Index (IPI) prognostic features, as defined by the presence of ≥ 3 of the following: Age > 60 years Tumor stage III or IV Extranodal disease at > 1 site ECOG performance status ≥ 2 Serum lactic dehydrogenase (LDH) > upper limit of normal (ULN) Intermediate- or high-grade NHL meeting 1 of the following criteria: In second or subsequent remission Failed to achieve a CR after initial chemotherapy Waldenstrom's macroglobulinemia meeting 1 of the following criteria: In second or subsequent remission Failed to achieve a CR after initial chemotherapy Multiple myeloma meeting 1 of the following criteria: In first or subsequent remission Failed to achieve a CR after initial chemotherapy Myeloproliferative disorders, including any of the following: Chronic myelogenous leukemia in first or subsequent chronic phase Myelofibrosis Essential thrombocytopenia that is poorly responsive to standard therapy Polycythemia vera that is poorly responsive to standard therapy or is in spent phase Prolymphocytic leukemia meeting 1 of the following criteria: In first or subsequent remission Failed to achieve a CR after initial chemotherapy Mantle cell lymphoma meeting 1 of the following criteria: In first or subsequent remission Failed to achieve a CR after initial chemotherapy Hodgkin's lymphoma meeting the following criteria: In second or subsequent remission Prior remission duration > 6 months No radiation therapy as the only prior primary therapy Myelodysplastic syndromes (MDS) meeting 1 of the following criteria: Refractory anemia with excess blasts (RAEB) RAEB in transformation Chronic myelomonocytic leukemia Any MDS with transfusion dependence Any MDS with ≥ 2 significant infections Acute myeloid leukemia in morphologic remission In CR or partial remission or stabilization of disease after standard chemotherapy No progressive or refractory disease Not eligible for standard allogeneic bone marrow transplantation Meets 1 of the following criteria: Age 60 to 75 years old AND no co-morbid illness Younger patients with any of the following comorbidities: Decreased cardiac ejection fraction Pulmonary dysfunction Elevated liver function tests Hepatitis C infection Poor performance status Sibling or related donor available Matched ≥ 5/6 HLA loci (A, B, and DR) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: See Disease Characteristics ECOG performance status 0-2 Creatinine < 2.0 mg/dL Creatinine clearance > 40 mL/min Ejection fraction > 30% by echocardiogram or MUGA Bilirubin < 3.0 mg/dL (if total bilirubin is elevated and Gilbert's disease is suspected, direct bilirubin must be normal) Alkaline phosphatase < 4 times ULN AST < 4 times ULN HIV negative Hepatitis B and/or C virus allowed if a liver biopsy (performed within the past 3 months) shows ≤ grade 2 inflammation No active infection PRIOR CONCURRENT THERAPY: See Disease Characteristics

Sites / Locations

  • Alta Bates Comprehensive Cancer Center
  • UCSF Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

stem cell transplant

Arm Description

Outcomes

Primary Outcome Measures

Toxicity and survival

Secondary Outcome Measures

Full Information

First Posted
February 23, 2006
Last Updated
October 2, 2012
Sponsor
University of California, San Francisco
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00296023
Brief Title
Donor Stem Cell Transplant in Treating Older or Frail Patients With Hematologic Cancer
Official Title
Low-Dose Allogeneic Peripheral Blood Stem Cell Transplantation for High-Risk Low Grade Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
January 1999 (undefined)
Primary Completion Date
June 2007 (Actual)
Study Completion Date
June 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and methotrexate and tacrolimus after the transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects of donor stem cell transplant in treating older or frail patients with hematologic cancer.
Detailed Description
OBJECTIVES: Primary Determine the safety of non-myeloablative allogeneic peripheral blood stem cell transplantation, in terms of regimen-related organ toxicity and toxicity from acute graft-vs-host disease (GVHD), in older or medically frail patients with high-risk indolent hematologic malignancies. Determine overall survival, disease-free survival, and relapse risk at 1, 2, and 3 years post-transplantation in these patients. Secondary Determine the engraftment of donor hematopoiesis at 6 weeks, 3 and 6 months, and 1 year post-transplantation in these patients. Determine the incidence and severity of chronic GVHD in older and medically infirm patients treated with this regimen. Determine the safety and efficacy of collecting peripheral blood stem cells from older donors (age > 60 years). Determine the need and efficacy of donor lymphocyte infusions in patients with residual disease after transplant. OUTLINE: Non-myeloablative preparative regimen:Patients receive fludarabine IV over 30 minutes on days -7 to -3, busulfan IV over 2 hours every 8 hours on days -4 and -3, and anti-thymocyte globulin IV over 8 hours on days -4 to -1. Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts recover. Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus orally every 12 hours or IV continuously beginning on day -2 and continuing until day 90, followed by a taper until day 180. Patients also receive methotrexate IV over 15-30 minutes on days 1, 3, 6, and 11. Donor lymphocyte infusions (DLIs): Patients with residual disease ≥ 6 months post-transplantation who are off immunosuppression for ≥ 30 days with no evidence of GVHD may receive DLIs. DLIs are administered ≥ 12 weeks apart in the presence of persistent disease, absence of severe (grade 3-4) GVHD, and absence of persistent GVHD after the first DLI. After completion of study therapy, patients are followed periodically for 5 years. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
Keywords
stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, stage III adult diffuse small cleaved cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, noncontiguous stage II marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, noncontiguous stage II adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage IV adult diffuse mixed cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, noncontiguous stage II mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, stage II multiple myeloma, stage III multiple myeloma, chronic phase chronic myelogenous leukemia, primary myelofibrosis, polycythemia vera, prolymphocytic leukemia, stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, chronic myelomonocytic leukemia, adult acute myeloid leukemia in remission, secondary acute myeloid leukemia, Waldenström macroglobulinemia, essential thrombocythemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, 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), noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, stage I multiple myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
stem cell transplant
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
anti-thymocyte globulin
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Biological
Intervention Name(s)
therapeutic allogeneic lymphocytes
Intervention Type
Drug
Intervention Name(s)
busulfan
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Type
Drug
Intervention Name(s)
tacrolimus
Intervention Type
Procedure
Intervention Name(s)
nonmyeloablative allogeneic hematopoietic stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Primary Outcome Measure Information:
Title
Toxicity and survival
Time Frame
up to 36 months post transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of a high-risk indolent hematologic malignancy meeting the following criteria: Chronic lymphocytic leukemia (CLL) meeting 1 of the following criteria: In second or subsequent remission Failed to achieve a complete remission (CR) after chemotherapy Non-Hodgkin's lymphoma (NHL) meeting 1 of the following criteria: Low-grade NHL meeting 1 of the following criteria: Standard-risk disease in second or subsequent remission Standard-risk disease and failed to achieve a CR after chemotherapy In first or subsequent remission with adverse International Prognostic Index (IPI) prognostic features, as defined by the presence of ≥ 3 of the following: Age > 60 years Tumor stage III or IV Extranodal disease at > 1 site ECOG performance status ≥ 2 Serum lactic dehydrogenase (LDH) > upper limit of normal (ULN) Intermediate- or high-grade NHL meeting 1 of the following criteria: In second or subsequent remission Failed to achieve a CR after initial chemotherapy Waldenstrom's macroglobulinemia meeting 1 of the following criteria: In second or subsequent remission Failed to achieve a CR after initial chemotherapy Multiple myeloma meeting 1 of the following criteria: In first or subsequent remission Failed to achieve a CR after initial chemotherapy Myeloproliferative disorders, including any of the following: Chronic myelogenous leukemia in first or subsequent chronic phase Myelofibrosis Essential thrombocytopenia that is poorly responsive to standard therapy Polycythemia vera that is poorly responsive to standard therapy or is in spent phase Prolymphocytic leukemia meeting 1 of the following criteria: In first or subsequent remission Failed to achieve a CR after initial chemotherapy Mantle cell lymphoma meeting 1 of the following criteria: In first or subsequent remission Failed to achieve a CR after initial chemotherapy Hodgkin's lymphoma meeting the following criteria: In second or subsequent remission Prior remission duration > 6 months No radiation therapy as the only prior primary therapy Myelodysplastic syndromes (MDS) meeting 1 of the following criteria: Refractory anemia with excess blasts (RAEB) RAEB in transformation Chronic myelomonocytic leukemia Any MDS with transfusion dependence Any MDS with ≥ 2 significant infections Acute myeloid leukemia in morphologic remission In CR or partial remission or stabilization of disease after standard chemotherapy No progressive or refractory disease Not eligible for standard allogeneic bone marrow transplantation Meets 1 of the following criteria: Age 60 to 75 years old AND no co-morbid illness Younger patients with any of the following comorbidities: Decreased cardiac ejection fraction Pulmonary dysfunction Elevated liver function tests Hepatitis C infection Poor performance status Sibling or related donor available Matched ≥ 5/6 HLA loci (A, B, and DR) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: See Disease Characteristics ECOG performance status 0-2 Creatinine < 2.0 mg/dL Creatinine clearance > 40 mL/min Ejection fraction > 30% by echocardiogram or MUGA Bilirubin < 3.0 mg/dL (if total bilirubin is elevated and Gilbert's disease is suspected, direct bilirubin must be normal) Alkaline phosphatase < 4 times ULN AST < 4 times ULN HIV negative Hepatitis B and/or C virus allowed if a liver biopsy (performed within the past 3 months) shows ≤ grade 2 inflammation No active infection PRIOR CONCURRENT THERAPY: See Disease Characteristics
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas G. Martin, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Willis Navarro, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Charles A. Linker, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Alta Bates Comprehensive Cancer Center
City
Berkeley
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Name
UCSF Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-0324
Country
United States

12. IPD Sharing Statement

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Donor Stem Cell Transplant in Treating Older or Frail Patients With Hematologic Cancer

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