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Melphalan in Patients With Neoplastic Meningitis

Primary Purpose

Brain and Central Nervous System Tumors, Extragonadal Germ Cell Tumor, Leukemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
melphalan
Sponsored by
Duke University
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring recurrent childhood acute lymphoblastic leukemia, recurrent adult Hodgkin lymphoma, Waldenström macroglobulinemia, recurrent childhood lymphoblastic lymphoma, childhood central nervous system germ cell tumor, recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, recurrent/refractory childhood Hodgkin lymphoma, recurrent ovarian germ cell tumor, recurrent adult non-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, extragonadal germ cell tumor, leptomeningeal metastases, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma

Eligibility Criteria

3 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed malignancy that is metastatic to the CSF or leptomeningeal/subarachnoid space, including the following: Leukemia Lymphoma Germ cell tumors Persistent or recurrent disease required Cytologic evidence of malignancy in CSF or evidence of leptomeningeal tumor by CT or MRI No obstructive hydrocephalus or complete block of spinal CSF pathways on pre- study MRI or CT No rapidly progressing or deteriorating neurological deficit PATIENT CHARACTERISTICS: Age: 3 and over Performance status: Karnofsky 60-100% (age 10 and over) OR Lansky 60-100% (age under 10) Life expectancy: At least 8 weeks Hematopoietic: Absolute neutrophil count greater than 1,000/mm3* Platelet count greater than 100,000/mm3* * Lower values allowed with approval of the investigator Hepatic: Bilirubin less than 3.0 mg/dL Renal: Creatinine less than 2 mg/dL Blood urea nitrogen less than 30 mg/dL Electrolytes (including calcium, magnesium, phosphate) normal Other: No active infection Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Prior systemic chemotherapy within 3 weeks of entry allowed at investigator's discretion At least 3 weeks since prior intrathecal chemotherapy No other concurrent intrathecal chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since prior radiotherapy to the CNS No concurrent radiotherapy to the CNS Surgery: Not specified

Sites / Locations

  • Duke Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
February 15, 2013
Sponsor
Duke University
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1. Study Identification

Unique Protocol Identification Number
NCT00002750
Brief Title
Melphalan in Patients With Neoplastic Meningitis
Official Title
Phase I of Intrathecal Melphalan in Patients With Recurrent Neoplastic Meningitis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
December 1992 (undefined)
Primary Completion Date
May 2001 (Actual)
Study Completion Date
May 2001 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of melphalan in patients with persistent or recurrent neoplastic meningitis.
Detailed Description
OBJECTIVES: I. Determine the maximum tolerated dose of intrathecal melphalan (L-PAM) in patients with neoplastic meningitis. II. Determine the CSF and serum pharmacokinetics of L-PAM administered via an Ommaya reservoir to these patients. OUTLINE: This is a dose escalation study. Patients receive melphalan (L-PAM) intrathecally (IT) via lumbar puncture or Ommaya reservoir twice a week for 2 weeks. Cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 4 of 6 patients experience dose-limiting toxicity. At least 3 patients receive L-PAM via Ommaya reservoir at the MTD. Patients with objective or significant clinical response may receive additional L-PAM IT once a week for 2 consecutive weeks, every other week for 2 doses, and then monthly thereafter. Patients are followed every 12 weeks for 1 year or until disease progression. PROJECTED ACCRUAL: A minimum of 3 children and 3 adults per dose level will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors, Extragonadal Germ Cell Tumor, Leukemia, Lymphoma, Ovarian Cancer
Keywords
recurrent childhood acute lymphoblastic leukemia, recurrent adult Hodgkin lymphoma, Waldenström macroglobulinemia, recurrent childhood lymphoblastic lymphoma, childhood central nervous system germ cell tumor, recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, recurrent/refractory childhood Hodgkin lymphoma, recurrent ovarian germ cell tumor, recurrent adult non-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, extragonadal germ cell tumor, leptomeningeal metastases, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
6 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
melphalan

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed malignancy that is metastatic to the CSF or leptomeningeal/subarachnoid space, including the following: Leukemia Lymphoma Germ cell tumors Persistent or recurrent disease required Cytologic evidence of malignancy in CSF or evidence of leptomeningeal tumor by CT or MRI No obstructive hydrocephalus or complete block of spinal CSF pathways on pre- study MRI or CT No rapidly progressing or deteriorating neurological deficit PATIENT CHARACTERISTICS: Age: 3 and over Performance status: Karnofsky 60-100% (age 10 and over) OR Lansky 60-100% (age under 10) Life expectancy: At least 8 weeks Hematopoietic: Absolute neutrophil count greater than 1,000/mm3* Platelet count greater than 100,000/mm3* * Lower values allowed with approval of the investigator Hepatic: Bilirubin less than 3.0 mg/dL Renal: Creatinine less than 2 mg/dL Blood urea nitrogen less than 30 mg/dL Electrolytes (including calcium, magnesium, phosphate) normal Other: No active infection Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Prior systemic chemotherapy within 3 weeks of entry allowed at investigator's discretion At least 3 weeks since prior intrathecal chemotherapy No other concurrent intrathecal chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since prior radiotherapy to the CNS No concurrent radiotherapy to the CNS Surgery: Not specified
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henry S. Friedman, MD
Organizational Affiliation
Duke Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Duke Comprehensive Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

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Melphalan in Patients With Neoplastic Meningitis

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