Clinical trial NCT00134017: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-08-24
Enrollment: 142
Sex: ALL
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Percentage of Participants Who Develop Acute Graft-versus-host Disease (GVHD)
timeFrame: Day 100
Secondary outcomes:
measure: Days to Engraftment
timeFrame: Up to one year
measure: Chimerism
timeFrame: Day 30, Day 60
measure: Non-relapse Mortality
timeFrame: Day 100, 2 years
measure: Relapse
timeFrame: 2 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Leo Luznik, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.