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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00022555
First received: August 10, 2001
Last updated: January 24, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
AIDS-related Diffuse Large Cell Lymphoma
AIDS-related Diffuse Mixed Cell Lymphoma
AIDS-related Peripheral/Systemic Lymphoma
AIDS-related Small Noncleaved Cell Lymphoma
Drug: bryostatin 1
Drug: vincristine sulfate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Combination Bryostatin-1 and Vincristine in HIV-Related B-cell Neoplasms

Resource links provided by NLM:


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

Primary Outcome Measures:
  • MTD of bryostatin-1 defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Dose-limiting toxicities [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Immunomodulatory effects of this combination [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Measured by a solid phase Enzyme Amplified Sensitivity Immunoassay.


Enrollment: 12
Study Start Date: November 2001
Primary Completion Date: July 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bryostatin 1, vincristine sulfate)
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.
Drug: bryostatin 1
Given IV
Other Names:
  • B705008K112
  • BRYO
  • Bryostatin
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00022555

Locations
United States, Maryland
AIDS - Associated Malignancies Clinical Trials Consortium
Rockville, Maryland, United States, 20850
Sponsors and Collaborators
Investigators
Principal Investigator: Scot Remick AIDS Associated Malignancies Clinical Trials Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00022555     History of Changes
Other Study ID Numbers: NCI-2012-02398, AMC-029, U01CA070019, CDR0000068830
Study First Received: August 10, 2001
Last Updated: January 24, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large B-Cell, Diffuse
Lymphoma, AIDS-Related
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Lymphoma, B-Cell
Vincristine
Bryostatin 1
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 14, 2014