Bryostatin 1 Plus Vincristine in Treating Patients With Recurrent or Refractory HIV-Related Lymphoma

AIDS-related Peripheral/Systemic Lymphoma Clinical Trial

Official title:

A Phase I Trial of Combination Bryostatin-1 and Vincristine in HIV-Related B-cell Neoplasms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00022555
• Other study ID #: NCI-2012-02398
• Secondary ID: AMC-029U01CA0700
• Status: Completed
• Phase: Phase 1
• First received: August 10, 2001
• Last updated: January 24, 2013
• Start date: November 2001

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Phase I trial to study the effectiveness of bryostatin 1 plus vincristine in treating patients who have recurrent or refractory lymphoma. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bryostatin 1 may help vincristine kill more cancer cells by making them more sensitive to the drug

Description:

OBJECTIVES:

I. Determine the maximum tolerated dose of bryostatin 1 when administered with vincristine in patients with recurrent or refractory HIV-related B-cell lymphoma.

II. Determine the toxicity profile of this regimen in these patients. III. Determine the objective response and survival of these patients treated with this regimen.

IV. Determine the immunomodulatory effects of this regimen on interleukin-2 (IL-2), IL-2 receptor, and IL-6 cytokine levels in these patients.

V. Determine the effect of this regimen on CD4+ lymphocyte count and HIV load in these patients.

VI. Determine the effect of this regimen on the human herpes virus-8 load in these patients with body cavity-based lymphoma.

OUTLINE: This is a multicenter, dose-escalation study of bryostatin 1.

Patients receive bryostatin 1 IV continuously on days 1 and 15 and vincristine IV over 5 minutes on days 2 and 16. Treatment continues every 4 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bryostatin 1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. primary completion date: July 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed B-cell lymphoma

• Eligible subtypes:

• Intermediate or high-grade non-Hodgkin's lymphoma (NHL), defined as follicular large cell, mantle cell, diffuse mixed cell, diffuse large cell and variants, Burkitt or Burkitt-like, or unclassifiable aggressive histologies

• Body cavity-based lymphoma or primary effusion lymphoma

• Evidence of HIV infection

• Received at least 1 prior systemic chemotherapy regimen with failure to respond or relapse after completion of first-line therapy, including one of the following doxorubicin-based combinations:

• Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)

• Infusional cyclophosphamide, doxorubicin, and etoposide (CDE)

• Etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH)

• Evaluable disease outside of prior radiation port

• No CNS parenchymal or leptomeningeal involvement

• No primary CNS NHL

• No HTLV-1-associated leukemia or lymphoma

• Performance status - Karnofsky 70-100%

• At least 12 weeks

• Absolute granulocyte count at least 1,000/mm3

• Platelet count at least 75,000/mm3

• Hemoglobin at least 8.0 g/dL

• Bilirubin no greater than 1.5 mg/dL (unless concurrently on indinavir)

• SGOT and SGPT less than 3 times upper limit of normal

• Creatinine no greater than 1.5 mg/dL

• Creatinine clearance at least 50 mL/min

• No history of cardiac disease

• LVEF at least 45% by radionuclide ventriculography

• No symptomatic congestive heart failure

• No active angina pectoris

• No uncontrolled hypertension

• No history of symptomatic pulmonary disease

• Corrected DLCO more than 50% predicted

• No severe chronic obstructive lung disease

• No symptomatic restrictive lung disease

• Recurrent controllable infection (e.g., thrush) on chronic suppressive therapy allowed

• No active uncontrolled infection

• No active significant opportunistic infection (e.g., acute Pneumocystis pneumonia, cytomegalovirus retinitis on induction or maintenance therapy, acute toxoplasmosis)

• No grade 2 or greater peripheral neuropathy

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception

• At least 24 hours since prior transfusion

• At least 24 hours since prior colony-stimulating factor therapy

• No concurrent prophylactic filgrastim (G-CSF)

• See Disease Characteristics

• No concurrent hydroxyurea

• See Disease Characteristics

• At least 4 weeks since prior large-field radiotherapy

• At least 3 weeks since prior anticancer therapy and recovered

• Must be receiving stable antiretroviral regimen of at least 4 weeks duration

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• AIDS-related Diffuse Large Cell Lymphoma
• AIDS-related Diffuse Mixed Cell Lymphoma
• AIDS-related Peripheral/Systemic Lymphoma
• AIDS-related Small Noncleaved Cell Lymphoma
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• bryostatin 1
Given IV
• vincristine sulfate
Given IV

Locations

Country	Name	City	State
United States	AIDS - Associated Malignancies Clinical Trials Consortium	Rockville	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD of bryostatin-1 defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity		4 weeks	Yes
Secondary	Dose-limiting toxicities	Defined as any >= grade 2 neuropathy, other grade 3 non-hematologic toxicity (excluding alopecia and grade 3 nausea and vomiting that is responsive to standard pharmacologic intervention) or grade 4 hematologic toxicity in 2 or more patients. The incidence of toxicity related dose reduction and treatment discontinuation will be summarized for each dose group.	4 weeks	Yes
Secondary	Immunomodulatory effects of this combination	Measured by a solid phase Enzyme Amplified Sensitivity Immunoassay.	Up to 2 years	No