Combining Chemotherapy, Tacrolimus, Mycophenolate Mofetil, and Radiation Therapy With Donor Bone Marrow Transplant in Treating Patients With Hematologic Cancer - Full Text View

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00049504

Purpose

RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor bone marrow transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune system cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving chemotherapy, tacrolimus, mycophenolate mofetil, and radiation therapy together with allogeneic bone marrow transplant works in treating patients with hematologic cancer.

Condition	Intervention	Phase
Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Drug: cyclophosphamide Drug: filgrastim Drug: fludarabine phosphate Drug: mycophenolate mofetil Drug: tacrolimus Procedure: allogeneic bone marrow transplantation Procedure: graft-versus-tumor induction therapy Procedure: radiation therapy	Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma Multiple Myeloma

Drug Information available for: Cyclophosphamide Filgrastim Fludarabine Fludarabine monophosphate Tacrolimus Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Tacrolimus anhydrous

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Nonmyeloablative Hematopoietic Stem Cell Transplantation for Patients With High-Risk Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Phase II Trial of Combined Immunosuppression Before and After Transplantation

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety [ Designated as safety issue: Yes ]

Estimated Enrollment:	50
Study Start Date:	January 2002
Estimated Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the efficacy of combined immunosuppression before and after nonmyeloablative HLA-haploidentical bone marrow transplantation, in terms of donor engraftment at day 84, in patients with high-risk hematologic malignancies.
Determine the safety of this regimen, in terms of incidence and severity of graft-vs-host disease and non-relapse-related mortality at day 200, in these patients.

OUTLINE:

Conditioning regimen: Patients receive fludarabine IV over 1 hour on days -6 to -2, cyclophosphamide IV over 1 hour on days -6 and -5, and total body irradiation on day -1.
Bone marrow infusion: Bone marrow from an HLA-haploidentical donor is infused on day 0.
Post-transplant immunosuppression: Patients receive cyclophosphamide IV over 1 hour on day 3.
Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV over 4 hours or orally (when tolerated) beginning on day 4 and continuing until day 180 in the absence of GVHD. Oral mycophenolate mofetil is administered three times daily on days 4-35.

Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 4 and continuing until blood counts recover.

Patients are followed annually.

PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study within 15-30 months.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of any of the following hematologic malignancies:
- Chronic myelogenous leukemia in accelerated phase
- Acute myeloid leukemia (AML) in first complete remission (CR) with the following high-risk cytogenetics:
  - del(5q)/-5, del(7q)/-7, abnormal 3q, 9q, 11q, 20q, 21q, 17p, t(6;9), t(9;22), complex karyotypes (at least 3 abnormalities)
- AML in at least second CR with less than 5% marrow blasts
- High-risk acute lymphoblastic leukemia with less than 5% marrow blasts
  - First CR with the following high-risk cytogenetics:
    - t(9;22), t(4;11), or hypodiploid (less than 45 chromosomes) for children
    - t(9;22), t(8;14), t(4;11), t(1;19) for adults
  - More than 4 weeks to achieve first CR
  - At least second CR
- Myelodysplastic syndromes after at least 1 prior course of induction chemotherapy and less than 5% marrow blasts
- Stage II or III multiple myeloma, meeting 1 of the following:
  - Progressed after an initial response to chemotherapy or autologous hematopoietic stem cell transplantation (HSCT)
  - Refractory disease which may benefit from tandem autologous non-myeloablative allogeneic transplantation
- Chronic lymphocytic leukemia, non-Hodgkin's lymphoma, or Hodgkin's lymphoma
  - Ineligible for autologous HSCT
Related donor available
- Identical for 1 HLA haplotype and mismatched at the HLA-A, -B, -C, or DRB1 loci of the unshared haplotype
- No single HLA-A, -B, or -C allele mismatches
- No HLA-mismatch only in the HVG direction
- Not cross-match positive
No suitably matched related or unrelated donor
No conventional transplantation options
No CNS involvement refractory to intrathecal chemotherapy

PATIENT CHARACTERISTICS:

Age

Any age

Performance status

Karnofsky 60-100% (adults)
Lansky 60-100% (children)

Life expectancy

Not severely limited by disease other than malignancy

Hematopoietic

See Disease Characteristics

Hepatic

No fulminant liver failure
No cirrhosis of the liver with portal hypertension
No alcoholic hepatitis
No esophageal varices
No hepatic encephalopathy
No uncorrectable hepatic synthetic dysfunction (prolonged prothrombin time)
No ascites related to portal hypertension
No bacterial or fungal liver abscess
No biliary obstruction
No chronic viral hepatitis
No symptomatic biliary disease
Bilirubin no greater than 3 mg/dL

Renal

Not specified

Cardiovascular

LVEF at least 35%

Pulmonary

DLCO at least 35%
No concurrent supplemental continuous oxygen

Other

HIV negative
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 1 year after study participation
No active serious infection (e.g., mucormycosis, uncontrolled aspergillosis, or tuberculosis)

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
No prior allogeneic HSCT unless allograft was rejected and there is no evidence of donor hematopoietic engraftment

Chemotherapy

See Disease Characteristics

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049504

Locations

United States, Washington
Fred Hutchinson Cancer Research Center	Recruiting
Seattle, Washington, United States, 98109-1024
Contact: Paul V. O'Donnell, MD, PhD 206-667-1968
Seattle Cancer Care Alliance	Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Clinical Trials Office - Seattle Cancer Care Alliance 800-804-8824

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Paul V. O'Donnell, MD, PhD

Fred Hutchinson Cancer Research Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	Fred Hutchinson Cancer Research Center ( Paul V. O'Donnell )
Study ID Numbers:	CDR0000258112, FHCRC-1667.00, NCI-H02-0098
Study First Received:	November 12, 2002
Last Updated:	December 31, 2008
ClinicalTrials.gov Identifier:	NCT00049504
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
refractory chronic lymphocytic leukemia
relapsing chronic myelogenous leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
de novo myelodysplastic syndromes
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 Burkitt 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
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent childhood large cell lymphoma

Study placed in the following topic categories:

Chronic myelogenous leukemia
Hodgkin lymphoma, adult
Lymphoma, Mantle-Cell
Mycophenolic Acid
Lymphoma, small cleaved-cell, diffuse
Tacrolimus
Small non-cleaved cell lymphoma
Lymphoma, large-cell, immunoblastic
Preleukemia
Hemorrhagic Disorders
Multiple myeloma
Leukemia, Lymphocytic, Chronic, B-Cell
Mycophenolate mofetil
Neoplasm Metastasis
Acute myeloid leukemia, adult

Hodgkin Disease
Chronic lymphocytic leukemia
Myelodysplastic syndromes
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, B-cell, chronic
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Blood Coagulation Disorders
Acute myelogenous leukemia
Myeloproliferative Disorders
Leukemia, Myeloid
Multiple Myeloma
Myelodysplastic myeloproliferative disease

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Disease
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Antibiotics, Antineoplastic

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Pathologic Processes
Syndrome
Therapeutic Uses
Myeloablative Agonists
Cardiovascular Diseases
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 15, 2009