Melphalan, Fludarabine, and Alemtuzumab Followed by Peripheral Stem Cell Transplant in Treating Patients With Hematologic Cancer - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00027560

Purpose

RATIONALE: Giving low doses of chemotherapy, such as melphalan and fludarabine, and a monoclonal antibody, such as alemtuzumab, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system 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 cyclosporine after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well fludarabine, melphalan, alemtuzumab, and peripheral stem cell transplant work in treating patients with hematologic cancer.

Condition	Intervention	Phase
Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms	Biological: alemtuzumab Drug: cyclosporine Drug: fludarabine phosphate Drug: melphalan Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation	Phase II

Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
Official Title:	Phase II Trial Of Non-Myeloablative Regimen Combining Melphalan, Fludarabine, And Anti-CD52 Monoclonal Antibody (CAMPATH-1H) Followed By An Unmodified Hematopoietic Cell Transplant From An HLA Compatible Related Or Unrelated Donor For Treatment Of Lymphohematopoietic Malignancies

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Acute Lymphocytic Leukemia Acute Myeloid Leukemia Bone Marrow Transplantation Cancer Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Leukemia Lymphoma Multiple Myeloma Myelodysplastic Syndromes

Drug Information available for: Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Campath Alemtuzumab Melphalan Sarcolysin Melphalan hydrochloride

U.S. FDA Resources

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

Primary Outcome Measures:

Durable hematopoietic reconstitution [ Designated as safety issue: No ]
Incidence and characteristics of peritransplantation morbidity and mortality [ Designated as safety issue: No ]
Incidence and severity of acute and chronic graft-versus-host disease [ Designated as safety issue: No ]
Overall and disease-free survival at 1, 3, 6, 12, and 24 months after transplantation [ Designated as safety issue: No ]

Secondary Outcome Measures:

Quality of bone marrow and peripheral blood chimerism at 1, 3, 6, 12, and 24 months after transplantation [ Designated as safety issue: No ]
Kinetics of immune reconstitution [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	July 2001
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Evaluate the proportion of patients with lymphohematopoietic malignancies who achieve durable hematopoietic reconstitution after receiving a nonmyeloablative regimen comprising melphalan, fludarabine, and alemtuzumab followed by allogeneic hematopoietic stem cell transplantation.
Determine the incidence and characteristics of peritransplantation morbidity and mortality (e.g., hepatic veno-occlusive disease or infections) in patients treated with this regimen.
Determine the incidence and severity of acute and chronic graft-versus-host disease in these patients treated with this regimen.
Determine the overall and disease-free survival at 1, 3, 6, 12, and 24 months after transplantation in these patients.
Determine the quality of bone marrow and peripheral blood chimerism at 1, 3, 6, 12, and 24 months after transplantation in these patients.
Assess the kinetics of immune reconstitution in patients treated with this regimen.

OUTLINE: Patients are stratified according to donor type (HLA-matched related vs HLA-matched unrelated, single HLA-allele disparate related, or unmatched) (HLA-mismatched related or matched unrelated donor stratum closed to accrual as of 1/11/06).

Patients receive a nonmyeloablative regimen comprising alemtuzumab IV over 8 hours on days -8 to -5, fludarabine IV over 30 minutes on days -8 to -4, and melphalan IV over 30 minutes on days -3 and -2. Allogeneic peripheral blood stem cells or bone marrow is infused on day 0.

Patients receive graft-versus host disease prophylaxis comprising cyclosporine IV every 12 hours beginning on day -1 and continuing orally as tolerated until day 100.

Patients are followed every 6 weeks for 6 months, every 3 months for 6 months, every 3-6 months for 1 year, and then annually thereafter or as clinically indicated.

PROJECTED ACCRUAL: A maximum of 50 patients (25 HLA-matched related and 25 HLA-mismatched related or matched unrelated) will be accrued for this study within 2 years (HLA-mismatched related or matched unrelated donor stratum closed to accrual as of 1/11/06).

Eligibility

Ages Eligible for Study:	up to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of one of the following:
- Relapsed or primary refractory non-Hodgkin's lymphoma (NHL)
  - Aggressive NHL histologies allowed if the following criteria are met:
    - Chemosensitive/radiosensitive, nonprogressive, or stable on therapy
    - Ineligible for autologous hematopoietic stem cell transplantation because of disease in bone marrow
- Chemosensitive relapsed or refractory acute lymphoblastic leukemia or chronic lymphocytic leukemia
- Relapsed or primary refractory Hodgkin's lymphoma
- Stage II or III multiple myeloma
- Advanced or refractory Waldenstrom's macroglobulinemia
Ineligible for protocols involving myeloablative conditioning regimens by virtue of any of the following conditions:
- Advanced age
- Intensity of prior radiotherapy and/or chemotherapy
- History of prior toxicity associated with chemotherapy/radiotherapy
- Existing organ damage
Diagnosis of chronic myeloid leukemia, high-risk acute myelogenous leukemia, or myelodysplastic syndromes allowed if no alternative, active, higher priority allogeneic transplantation protocol exists
Availability of an HLA-matched or a single HLA allele disparate related or unrelated donor (HLA-mismatched related or matched unrelated donor stratum closed to accrual as of 1/11/06)
No uncontrolled CNS disease

PATIENT CHARACTERISTICS:

Age:

70 and under

Performance status:

Karnofsky 40-100%

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Bilirubin no greater than 2.5 mg/dL
AST and ALT no greater than 3 times normal unless due to liver involvement with disease

Renal:

Creatinine no greater than 2.0 mg/dL OR
Creatinine clearance at least 30 mL/min

Cardiovascular:

Resting LVEF at least 30% by echocardiogram or MUGA scan

Pulmonary:

DLCO at least 40% of predicted
No requirement for supplementary oxygen

Other:

HIV negative
HTLV negative
No active or uncontrolled bacterial, viral, or fungal infection that would preclude myelosuppressive chemotherapy
Not pregnant or nursing
Negative pregnancy test

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics

Chemotherapy:

See Disease Characteristics

Endocrine therapy

Not specified

Radiotherapy:

See Disease Characteristics

Surgery:

Not specified

Other:

Concurrent cardiac medication for congestive heart failure allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00027560

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Hugo R. Castro-Malaspina, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

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

No publications provided

ClinicalTrials.gov Identifier:	NCT00027560 History of Changes
Other Study ID Numbers:	CDR0000069043, MSKCC-01092, NCI-G01-2028
Study First Received:	December 7, 2001
Last Updated:	May 14, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent childhood acute lymphoblastic leukemia
recurrent adult Hodgkin lymphoma
refractory multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
recurrent childhood lymphoblastic lymphoma
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
recurrent/refractory childhood Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma

recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
previously treated myelodysplastic syndromes
recurrent childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma
recurrent mantle cell lymphoma
Waldenstrom macroglobulinemia
childhood chronic myelogenous leukemia
atypical chronic myeloid leukemia, BCR-ABL1 negative
myelodysplastic/myeloproliferative neoplasm, unclassifiable
recurrent marginal zone lymphoma

Additional relevant MeSH terms:

Neoplasms
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Cyclosporins
Cyclosporine
Melphalan
Fludarabine monophosphate
Campath 1G
Vidarabine

ClinicalTrials.gov processed this record on February 12, 2012