Combination Chemotherapy Plus Infusion of White Blood Cells in Treating Patients With Hematologic Cancer - Full Text View

Sponsored by:	Sidney Kimmel Comprehensive Cancer Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003243

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. White blood cells from donors may be able to kill cancer cells in patients who have hematologic cancer that has recurred following bone marrow transplantation.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus infusion of donated white blood cells in treating patients who have hematologic cancer that has recurred after bone marrow transplantation.

Condition	Intervention	Phase
Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: aldesleukin Biological: filgrastim Biological: therapeutic allogeneic lymphocytes Drug: cyclophosphamide Drug: etoposide Drug: pegylated liposomal doxorubicin hydrochloride	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Trial of Combined Chemotherapy and Donor Lymphocyte Infusion for Aggressive Hematologic Malignancies in Relapse After Allogeneic Bone Marrow Transplantation

Resource links provided by NLM:

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

Drug Information available for: Cyclophosphamide Doxorubicin Doxorubicin hydrochloride Etoposide Aldesleukin Myocet Filgrastim

U.S. FDA Resources

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

Study Start Date:

January 1998

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of doxorubicin HCl liposome when combined with etoposide, cyclophosphamide, and allogeneic donor lymphocyte infusion with or without interleukin-2 after allogeneic bone marrow transplantation in patients with relapsed or persistent aggressive hematologic malignancies.

OUTLINE: This is a partially randomized, dose-escalation study of doxorubicin HCl liposome (LipoDox).

Patients enter 1 of 4 cohorts.

Cohort 1: Three to six patients receive induction comprising etoposide IV over 1 hour on days 1-3, cyclophosphamide IV over 1-2 hours on day 8, and allogeneic donor lymphocyte infusion on day 10. Filgrastim (G-CSF) is administered subcutaneously (SC) or IV daily beginning on day 10 and continuing until blood counts recover.
Cohort 2: In the absence of dose-limiting toxicity (DLT) on cohort 1, 3-6 patients receive treatment as in cohort 1 and LipoDox IV over 2 hours on day 1.
Cohort 3: In the absence of DLT on cohort 2, 3-6 patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive treatment as in cohort 1 plus a higher dose of LipoDox IV over 2 hours on day 1.
- Arm II: Patients receive treatment as in cohort 1 and interleukin-2 (IL-2) SC on days 10-12.

If DLT is reached on cohort 2, 3-6 patients receive treatment as in arm II.

Cohort 4: In the absence of DLT on arms I and II, patients receive treatment as in cohort 1, LipoDox as in arm I, and IL-2 as in arm II. Cohorts of 3-6 patients receive escalating doses of LipoDox until the maximum tolerated dose (MTD) is determined.

The MTD is defined as the dose preceding that at which 2 of 6 patients experience DLT.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 12-15 patients will be accrued for this study within 12-18 months.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of relapsed or persistent acute leukemia, myelodysplasia, aggressive non-Hodgkin's lymphoma (NHL), or chronic myeloid leukemia in transformed phase (accelerated phase or blast crisis) after allogeneic bone marrow transplantation (BMT)
Aggressive NHL defined as diffuse mixed, diffuse large cell, diffuse small noncleaved cell, and lymphoblastic histologies
No active acute graft versus host disease (GVHD) or extensive chronic GVHD

PATIENT CHARACTERISTICS:

Age:

Not specified

Performance status:

ECOG 0-2

Life expectancy:

More than 4 weeks

Hematopoietic:

Not specified

Hepatic:

Not specified

Renal:

Not specified

Other:

No severe psychiatric illness or mental deficiencies

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics
At least 6 months since prior allogeneic BMT
No other concurrent interleukin-2
No other concurrent immunomodulatory medication (e.g., interferon)

Chemotherapy:

Not specified

Endocrine therapy:

No concurrent steroids

Radiotherapy:

Not specified

Surgery:

Not specified

Other:

No concurrent immunosuppressive medication (e.g., cyclosporine) for GVHD

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003243

Locations

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

Investigators

Study Chair:

Ephraim J. Fuchs, MD

Sidney Kimmel Comprehensive 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

Study ID Numbers:	CDR0000066119, JHOC-97112101, NCI-V98-1387
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00003243 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent childhood acute lymphoblastic leukemia
recurrent childhood lymphoblastic lymphoma
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
acute undifferentiated leukemia
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma

recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
secondary acute myeloid leukemia
previously treated myelodysplastic syndromes
recurrent childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma
childhood chronic myelogenous leukemia
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
childhood myelodysplastic syndromes

Study placed in the following topic categories:

Anti-Infective Agents
Blast Crisis
Preleukemia
Acute Myelocytic Leukemia
Acute Myeloid Leukemia, Adult
Neoplasm Metastasis
Aggression
Etoposide
Myelodysplastic Myeloproliferative Disease
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Anti-HIV Agents
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative

Myeloproliferative Disorders
Leukemia, Myeloid
Doxorubicin
Aldesleukin
Leukemia, Myeloid, Accelerated Phase
Chronic Myelogenous Leukemia
Acute Lymphoblastic Leukemia, Childhood
Leukemia, Lymphoid
Hematologic Neoplasms
Precancerous Conditions
Immunologic Factors
Cyclophosphamide
Leukemia, Myeloid, Acute
Lymphoblastic Lymphoma
Etoposide phosphate

Additional relevant MeSH terms:

Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Leukemia
Preleukemia
Pathologic Processes
Anti-Retroviral Agents
Therapeutic Uses
Syndrome
Alkylating Agents

Lymphoma
Anti-HIV Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Disease
Immune System Diseases
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Antiviral Agents
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Lymphatic Diseases
Neoplasms

ClinicalTrials.gov processed this record on September 01, 2009