Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin's Lymphoma

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2; Phase 1

Conditions: Lymphoma

Treatments: Drug: vinorelbine tartrate; Drug: gemcitabine hydrochloride; Drug: pegylated liposomal doxorubicin hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00006029

CLB-59804

CALGB-59804

CDR0000068042 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy in treating patients who have relapsed or refractory Hodgkin's lymphoma.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose and toxicity of gemcitabine, vinorelbine, and doxorubicin HCl liposome in patients with relapsed or refractory Hodgkin's lymphoma.
• Determine the complete and partial response rates of patients treated with this regimen.

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

Phase I:

• Patients receive vinorelbine IV over 6-10 minutes, gemcitabine IV over 30 minutes, and doxorubicin HCl liposome IV over 30-60 minutes on days 1 and 8. Treatment continues every 21 days for 2-6 courses in the absence of unacceptable toxicity or disease progression. Patients who respond to treatment after 2 or more courses may stop protocol therapy to undergo peripheral blood stem cell transplantation.

Cohorts of 3-6 patients receive escalating doses of vinorelbine, gemcitabine, and doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with gemcitabine, vinorelbine, and doxorubicin HCl liposome at the recommended phase II dose.

Phase II:

• Patients are assigned to 1 of 2 treatment groups.

  • Group 1: Patients who have not undergone prior transplantation receive vinorelbine, gemcitabine, and doxorubicin HCl liposome as in phase I.
  • Group 2: Patients who have undergone prior transplantation receive lower doses of vinorelbine, gemcitabine, and doxorubicin HCl liposome as in group 1.

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

PROJECTED ACCRUAL: Approximately 3-100 patients (3-42 for phase I and 20-58 for phase II [29 per group]) will be accrued for this study within 3 years.

Enrollment: 91 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed Hodgkin's lymphoma that is recurrent or refractory after standard chemotherapy

  • Core biopsy is acceptable if adequate tissue is obtained for primary diagnosis and immunophenotyping
  • Bone marrow biopsy is not acceptable as sole means of diagnosis

• Measurable disease

  • Tumor mass greater than 1 cm

PATIENT CHARACTERISTICS:

Age:

• Any age

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL unless history of Gilbert's disease
• AST no greater than 2 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• LVEF at least 45% by MUGA (for patients whose lifetime cumulative doxorubicin dose exceeds 400 mg/m^2)

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No prior gemcitabine, vinorelbine, or doxorubicin HCl liposome
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormones except for nondisease-related conditions (e.g., insulin for diabetes) or steroids for adrenal failure
• No concurrent dexamethasone or other steroidal antiemetics

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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91 participants in 2 patient groups

vinorelbine + gemcitabine + doxorubicin - higher doses

Active Comparator group

Description:

Patients who have not undergone prior transplantation receive vinorelbine, gemcitabine, and doxorubicin HCl liposome. Patients are followed every 6 months for 2 years and then annually for 6 years.

Treatment:

Drug: pegylated liposomal doxorubicin hydrochloride

Drug: vinorelbine tartrate

Drug: gemcitabine hydrochloride

vinorelbine + gemcitabine + doxorubicin - lower doses

Experimental group

Description:

Patients who have undergone prior transplantation receive lower doses of vinorelbine, gemcitabine, and doxorubicin HCl liposome. Patients are followed every 6 months for 2 years and then annually for 6 years.

Treatment:

Drug: pegylated liposomal doxorubicin hydrochloride

Drug: vinorelbine tartrate

Drug: gemcitabine hydrochloride