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HLA Matched Related and Unrelated Bone Marrow Transplantation With Busulfan/Cyclophosphamide and Post Transplantation Cyclophosphamide for Hematological Malignancies


Phase 2
N/A
65 Years
Not Enrolling
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

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Trial Information

HLA Matched Related and Unrelated Bone Marrow Transplantation With Busulfan/Cyclophosphamide and Post Transplantation Cyclophosphamide for Hematological Malignancies


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 1 of the following immunosuppressive
treatment regimens:

- Regimen 1: Patients receive high-dose cyclophosphamide IV over 1 hour on day 3.

- Regimen 2: Patients receive high-dose cyclophosphamide IV over 1 hour on days 3
and 4.

- Regimen 3: Patients receive high-dose cyclophosphamide as in regimen 2 and oral
mycophenolate mofetil three times daily on days 5-35.

- Regimen 4: Patients receive high-dose cyclophosphamide as in regimen 2 and
mycophenolate mofetil as in regimen 3. Patients also receive tacrolimus IV or
orally twice daily on days 5-50.

After completion of study transplantation, patients are followed at 30 and 60 days, 6
months, 1 year, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 30-60 patients (approximately 5 per immunosuppressive
treatment regimen) will be accrued for this study.

Inclusion 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)

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose Finding

Outcome Description:

To find the optimal dose of post-grafting immunosuppression with high-dose cyclophosphamide (Cy), FK-506 and MMF following myeloablative fully HLA-matched related or unrelated BMT for the patients with hematological malignancies who are at high risk of relapse. To estimate the incidence and severity of acute GVHD and other toxicities following myeloablative fully HLA-matched related or unrelated BMT using this approach for the patients with hematological malignancies

Outcome Time Frame:

Day 100

Safety Issue:

Yes

Principal Investigator

Leo Luznik, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000440164, J0373

NCT ID:

NCT00134017

Start Date:

May 2004

Completion Date:

January 2010

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • 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
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Lymphoma, Large-Cell, Immunoblastic
  • Hematologic Neoplasms

Name

Location

Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410