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Combination Chemotherapy, Bone Marrow Transplant, and Post Transplant Cyclophosphamide for Hematologic Cancer

Primary Purpose

Chronic Myeloproliferative Disorders, Leukemia, Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Busulfan
Cyclophosphamide
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring adult acute myeloid leukemia in remission, refractory anemia with excess blasts, 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), childhood acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia, de novo myelodysplastic syndromes, adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, chronic eosinophilic leukemia, chronic idiopathic myelofibrosis, chronic neutrophilic leukemia, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, stage II multiple myeloma, stage III multiple myeloma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, previously treated myelodysplastic syndromes, 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 immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent/refractory childhood Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, recurrent small lymphocytic lymphoma, recurrent marginal zone lymphoma, stage III adult Burkitt 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 adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult Burkitt 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 adult immunoblastic large cell 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, stage III mantle cell lymphoma, stage III marginal zone lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, chronic myelomonocytic leukemia, refractory chronic lymphocytic leukemia, refractory multiple myeloma, secondary myelodysplastic syndromes, stage IV adult lymphoblastic lymphoma, childhood myelodysplastic syndromes

Eligibility Criteria

6 Months - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of 1 of the following hematologic malignancies: Acute myeloid leukemia (AML), meeting 1 of the following criteria: AML beyond first complete remission (CR1) Refractory AML AML arising from myelodysplastic syndromes (MDS) Secondary AML MDS Refractory anemia with excess blasts with > 10% blasts in bone marrow Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria: ALL in CR1 with 1 of the following high-risk features: Philadelphia chromosome (Ph)-positive disease Less than 1 year of age at diagnosis Cytogenetic abnormalities involving chromosome 11q23 ALL beyond CR1 Refractory ALL Chronic myeloid leukemia beyond first chronic phase Chronic myelomonocytic leukemia Chronic lymphocytic leukemia Stage III-IV disease Does not meet criteria for other bone marrow transplantation (BMT) studies Myeloproliferative disorders Ph-negative disease Hodgkin's or non-Hodgkin's lymphoma Chemotherapy-resistant disease Paroxysmal nocturnal hemoglobinuria with life-threatening thrombosis Multiple myeloma Stage II or III disease Very high-risk disease Having an unrelated donor is considered a high-risk condition Meets medical criteria for myeloablative BMT for the Sidney Kimmel Comprehensive Cancer Center Bone marrow donor available, meeting 1 of the following criteria: Genotypically HLA-identical sibling Phenotypically matched first-degree relative Unrelated donor molecularly matched at HLA-A, -B, -C, -DRB1, and -DQB1 PATIENT CHARACTERISTICS: Age 6 months to 65 years Performance status Not specified Life expectancy Not specified Hematopoietic See Disease Characteristics Hepatic Not specified Renal Not specified Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics Endocrine therapy No concurrent dexamethasone as an antiemetic during immunosuppression therapy Radiotherapy Not specified Surgery Not specified Other No concurrent immunosuppressants until ≥ 24 hours after the completion of cyclophosphamide (post-transplantation)

Sites / Locations

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bone marrow transplant

Arm Description

Myeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis

Outcomes

Primary Outcome Measures

Percentage of Participants Who Develop Acute Graft-versus-host Disease (GVHD)
Percentage of participants who developed grades II-IV and grades III-IV acute GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).

Secondary Outcome Measures

Days to Engraftment
Median number of days to neutrophil and platelet engraftment.
Chimerism
Number of patients who achieved 100% donor chimerism.
Non-relapse Mortality
Percentage of participants who died for BMT-related reasons.
Relapse
Percentage of participants who developed relapse or progressive disease.

Full Information

First Posted
August 22, 2005
Last Updated
August 29, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00134017
Brief Title
Combination Chemotherapy, Bone Marrow Transplant, and Post Transplant Cyclophosphamide for Hematologic Cancer
Official Title
HLA Matched Related and Unrelated Bone Marrow Transplantation With Busulfan/Cyclophosphamide and Post Transplantation Cyclophosphamide for Hematological Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
June 2004 (Actual)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
February 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)

4. Oversight

Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer and abnormal cells and helps 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 cyclophosphamide, mycophenolate mofetil, or tacrolimus after transplant may stop this from happening. PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with tacrolimus and mycophenolate mofetil works in treating patients who are undergoing a donor bone marrow transplant for hematologic cancer.
Detailed Description
OBJECTIVES: Primary Determine the optimal dose of post-transplant immunosuppression comprising high-dose cyclophosphamide, tacrolimus, and mycophenolate mofetil administered after myeloablative conditioning chemotherapy comprising busulfan and cyclophosphamide followed by allogeneic bone marrow transplantation in patients with high-risk hematologic malignancies. Determine the incidence and severity of acute graft-versus-host disease in patients treated with this regimen. Determine other toxic effects of this regimen in these patients. Secondary Determine immune reconstitution in patients treated with this regimen. Determine disease control in patients treated with this regimen. OUTLINE: This is a pilot study. Patients are stratified according to age (≤ 19 years old vs > 19 years old). Myeloablative conditioning chemotherapy: Patients receive busulfan IV or orally 4 times daily on days -7 to -4 OR days -6 to -3 and cyclophosphamide IV over 1 hour once daily on days -3 to -1 OR days -2 and -1. Allogeneic bone marrow transplantation: Patients undergo allogeneic bone marrow transplantation on day 0. Immunosuppression therapy: Patients receive high-dose cyclophosphamide IV over 1 hour on days 3 and 4. After completion of study transplantation, patients are followed at 30 and 60 days, 6 months, 1 year, and then annually thereafter.

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
adult acute myeloid leukemia in remission, refractory anemia with excess blasts, 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), childhood acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia, de novo myelodysplastic syndromes, adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, chronic eosinophilic leukemia, chronic idiopathic myelofibrosis, chronic neutrophilic leukemia, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, stage II multiple myeloma, stage III multiple myeloma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, previously treated myelodysplastic syndromes, 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 immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent/refractory childhood Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, recurrent small lymphocytic lymphoma, recurrent marginal zone lymphoma, stage III adult Burkitt 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 adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult Burkitt 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 adult immunoblastic large cell 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, stage III mantle cell lymphoma, stage III marginal zone lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, chronic myelomonocytic leukemia, refractory chronic lymphocytic leukemia, refractory multiple myeloma, secondary myelodysplastic syndromes, stage IV adult lymphoblastic lymphoma, childhood myelodysplastic syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
142 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bone marrow transplant
Arm Type
Experimental
Arm Description
Myeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Myleran, Busulfex
Intervention Description
Days -7 to -4: 4 mg/kg PO daily OR 3.2 mg/kg IV daily OR 160 mg/m^2 daily (for pediatric recipients)
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan, CTX
Intervention Description
Days -3, -2, +3, +4: 50 mg/kg IV daily
Primary Outcome Measure Information:
Title
Percentage of Participants Who Develop Acute Graft-versus-host Disease (GVHD)
Description
Percentage of participants who developed grades II-IV and grades III-IV acute GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).
Time Frame
Day 100
Secondary Outcome Measure Information:
Title
Days to Engraftment
Description
Median number of days to neutrophil and platelet engraftment.
Time Frame
Up to one year
Title
Chimerism
Description
Number of patients who achieved 100% donor chimerism.
Time Frame
Day 30, Day 60
Title
Non-relapse Mortality
Description
Percentage of participants who died for BMT-related reasons.
Time Frame
Day 100, 2 years
Title
Relapse
Description
Percentage of participants who developed relapse or progressive disease.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of 1 of the following hematologic malignancies: Acute myeloid leukemia (AML), meeting 1 of the following criteria: AML beyond first complete remission (CR1) Refractory AML AML arising from myelodysplastic syndromes (MDS) Secondary AML MDS Refractory anemia with excess blasts with > 10% blasts in bone marrow Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria: ALL in CR1 with 1 of the following high-risk features: Philadelphia chromosome (Ph)-positive disease Less than 1 year of age at diagnosis Cytogenetic abnormalities involving chromosome 11q23 ALL beyond CR1 Refractory ALL Chronic myeloid leukemia beyond first chronic phase Chronic myelomonocytic leukemia Chronic lymphocytic leukemia Stage III-IV disease Does not meet criteria for other bone marrow transplantation (BMT) studies Myeloproliferative disorders Ph-negative disease Hodgkin's or non-Hodgkin's lymphoma Chemotherapy-resistant disease Paroxysmal nocturnal hemoglobinuria with life-threatening thrombosis Multiple myeloma Stage II or III disease Very high-risk disease Having an unrelated donor is considered a high-risk condition Meets medical criteria for myeloablative BMT for the Sidney Kimmel Comprehensive Cancer Center Bone marrow donor available, meeting 1 of the following criteria: Genotypically HLA-identical sibling Phenotypically matched first-degree relative Unrelated donor molecularly matched at HLA-A, -B, -C, -DRB1, and -DQB1 PATIENT CHARACTERISTICS: Age 6 months to 65 years Performance status Not specified Life expectancy Not specified Hematopoietic See Disease Characteristics Hepatic Not specified Renal Not specified Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics Endocrine therapy No concurrent dexamethasone as an antiemetic during immunosuppression therapy Radiotherapy Not specified Surgery Not specified Other No concurrent immunosuppressants until ≥ 24 hours after the completion of cyclophosphamide (post-transplantation)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leo Luznik, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-2410
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
20124511
Citation
Luznik L, Bolanos-Meade J, Zahurak M, Chen AR, Smith BD, Brodsky R, Huff CA, Borrello I, Matsui W, Powell JD, Kasamon Y, Goodman SN, Hess A, Levitsky HI, Ambinder RF, Jones RJ, Fuchs EJ. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010 Apr 22;115(16):3224-30. doi: 10.1182/blood-2009-11-251595. Epub 2010 Feb 2.
Results Reference
result

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Combination Chemotherapy, Bone Marrow Transplant, and Post Transplant Cyclophosphamide for Hematologic Cancer

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