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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00134017
• Other study ID #: J0373
• Secondary ID: P01CA015396P30CA
• Status: Completed
• Phase: Phase 2
• Start date: June 2004
• Est. completion date: February 2010

Study information

• Verified date: August 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myeloproliferative Disorders
• Neoplasms, Plasma Cell
• Plasmacytoma
• Preleukemia
• Syndrome

Intervention

Drug:
• Busulfan
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)
• Cyclophosphamide
Days -3, -2, +3, +4: 50 mg/kg IV daily

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Luznik L, Bolaños-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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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+).	Day 100
Secondary	Days to Engraftment	Median number of days to neutrophil and platelet engraftment.	Up to one year
Secondary	Chimerism	Number of patients who achieved 100% donor chimerism.	Day 30, Day 60
Secondary	Non-relapse Mortality	Percentage of participants who died for BMT-related reasons.	Day 100, 2 years
Secondary	Relapse	Percentage of participants who developed relapse or progressive disease.	2 years