Cyclophosphamide Plus Bone Marrow Transplantation in Treating Patients With Hematologic Cancer - Full Text View

Sponsor:	Sidney Kimmel Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00006042

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells.

PURPOSE: Phase I trial to study the effectiveness of cyclophosphamide plus bone marrow transplantation in treating patients who have hematologic cancer.

Condition	Intervention	Phase
Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: filgrastim Drug: cyclophosphamide Drug: fludarabine phosphate Drug: mycophenolate mofetil Drug: tacrolimus Procedure: allogeneic bone marrow transplantation Radiation: radiation therapy	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Non-Myeloablative Allogeneic Bone Marrow Transplantation for Hematologic Malignancies Using Haploidentical Donors: A Phase I Trial of Pre-Transplant Cyclophosphamide

Resource links provided by NLM:

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

Study Start Date:

December 1999

Detailed Description:

OBJECTIVES:

Determine the minimum effective dose of pretransplant cyclophosphamide to induce engraftment of haploidentical allogeneic bone marrow without the use of myeloablative conditioning in patients with hematologic malignancies.
Determine the incidence and severity of graft versus host disease and nonhematologic toxicities with this treatment regimen in these patients.
Correlate the pretreatment phenotypic and functional immunologic characteristics in these patients in relation to risk of graft rejection with this treatment regimen.

OUTLINE: This is a dose-escalation study of cyclophosphamide.

Patients receive fludarabine IV over 1 hour on days -6 to -2; cyclophosphamide IV over 1 hour on days -6, -5, and 3; total body irradiation on day -1; and allogeneic bone marrow transplantation on day 0. Patients also receive tacrolimus IV or orally twice a day on days 4-50; oral mycophenolate mofetil on days 4-35; and filgrastim (G-CSF) subcutaneously or IV starting on day 4 and continuing until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of cyclophosphamide until the minimum effective dose necessary to induce chimerism without unacceptable toxicity in these patients is determined.

Patients are followed at 2 and 6 months, at one year, and then annually thereafter.

PROJECTED ACCRUAL: At least 23 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Patients with any of the following diagnoses:
- Chronic myelogenous leukemia
  - Chronic phase 1
    - Failed prior interferon alfa therapy OR
    - Relapsed after prior autologous stem cell transplantation
  - Chronic phase 2
- Acute leukemia
  - Standard risk
    - Age over 60 years
    - Complete remission 1 (CR1)
  - High risk
    - High WBC at presentation, unfavorable cytogenetics, mixed lineage, delayed response to induction chemotherapy
    - CR1
    - Complete remission 2 or higher
- Acute lymphocytic leukemia
  - CR1 or higher
- Myelodysplastic syndrome
  - Untreated OR
  - CR1
- Acute myeloid leukemia in CR1
- Chronic lymphocytic leukemia
  - Rai stage III or IV OR
  - Received prior autologous stem cell transplantation
- Multiple myeloma
  - Stage II or III
  - Stable or progressive disease after prior chemotherapy OR
  - Received prior autologous stem cell transplantation
- Non-Hodgkin's Lymphoma
- Hodgkin's lymphoma
Ineligible for or refused autologous or standard allogeneic bone marrow transplantation
Ineligible for bone marrow transplantation from an HLA matched, sibling donor or from an HLA matched, unrelated donor
Must have an HLA mismatched, related donor (3-5 out of 6)

PATIENT CHARACTERISTICS:

Age:

0.5 to 70

Performance status:

ECOG 0-1

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Bilirubin less than 3.1 mg/dL

Renal:

Not specified

Cardiovascular:

Left ventricular ejection fraction at least 35%

Pulmonary:

FEV_1 and FVC at least 40% of predicted OR
FEV_1 and FVC at least 60% in patients who have received prior thoracic or mantle radiotherapy

Other:

HIV negative
No other debilitating medical or psychiatric illness that would preclude study compliance
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics
No prior transfusions from donor

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: NCT00006042

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

National Cancer Institute (NCI)

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

Publications:

O'Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, Rhubart P, Cowan K, Piantados S, Fuchs EJ. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8(7):377-86.

Study ID Numbers:	CDR0000068057, JHOC-J9966, JHOC-99110501, NCI-G00-1816
Study First Received:	July 5, 2000
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00006042 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult Hodgkin lymphoma
Burkitt lymphoma
refractory multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
recurrent childhood lymphoblastic lymphoma
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
chronic phase chronic myelogenous leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission

recurrent/refractory childhood Hodgkin lymphoma
stage II adult lymphoblastic lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma

Additional relevant MeSH terms:

Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Mycophenolic Acid
Tacrolimus
Preleukemia
Hemorrhagic Disorders
Pathologic Processes
Therapeutic Uses
Mycophenolate mofetil
Cardiovascular Diseases
Immunoproliferative Disorders
Immune System Diseases
Hematologic Diseases

Myeloproliferative Disorders
Multiple Myeloma
Neoplasms
Fludarabine
Lymphoma, Non-Hodgkin
Antimetabolites
Vidarabine
Precancerous Conditions
Immunologic Factors
Blood Protein Disorders
Antineoplastic Agents
Paraproteinemias
Cyclophosphamide
Antibiotics, Antineoplastic
Hemostatic Disorders

ClinicalTrials.gov processed this record on November 27, 2009