A Study of DCDS4501A in Combination With Rituximab, Cyclophosphamide, Doxorubicin and Prednisone in Patients With B-Cell Non-Hodgkin's Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01992653
First received: October 28, 2013
Last updated: October 20, 2014
Last verified: October 2014
  Purpose

This multicenter, open-label, dose-escalation study will evaluate the safety and anti-tumor activity of DCDS4501A in combination with rituximab, cyclophosphamid e, doxorubicin and prednisone in patients with non-Hodgkin's lymphoma. Cohort of patients will receive escalating doses of DCDS4501A intravenously every 3 weeks in combination with standard doses of rituximab, cyclophosphamide, doxorubicin and oral prednisone. Patients will be treated for a total of six or eight cycles in accordance with local institutional practice.


Condition Intervention Phase
Lymphoma, B-Cell, Non-Hodgkin's Lymphoma
Drug: DCDS4501A
Drug: cyclophosphamide
Drug: doxorubicin
Drug: prednisone
Drug: rituximab [MabThera/Rituxan]
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE Ib STUDY EVALUATING THE SAFETY, TOLERABILITY AND ANTI-TUMOR ACTIVITY OF DCDS4501A IN COMBINATION WITH RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, AND PREDNISONE IN PATIENTS WITH B-CELL NON-HODGKIN'S LYMPHOMA

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Safety: Incidence of adverse events [ Time Frame: up to approximately 40 weeks ] [ Designated as safety issue: No ]
  • Safety: Incidence of anti-DCDS4501A antibodies [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Dose-limiting toxicities [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics: Area under the concentration-time curve [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum concentration (Cmax) [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Clearance (CL) [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Terminal half-life (t1/2) [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Steady-state volume of distribution (Vss) [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ] [ Designated as safety issue: No ]
  • Objective response rate [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Complete response rate [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
  • Event-free survival [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: November 2013
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DCDS4501A Drug: DCDS4501A
escalating doses IV every 3 weeks, 6 or 8 cycles
Drug: cyclophosphamide
750 mg/m2 IV every 3 weeks, 6 or 8 cycles
Drug: doxorubicin
50 mg/m2 IV every 3 weeks, 6 or 8 cycles
Drug: prednisone
100 mg orally daily for five days every 3 weeks, 6 or 8 cycles
Drug: rituximab [MabThera/Rituxan]
375 mg/m2 IV every 3 weeks, 6 or 8 cycles

  Eligibility

Ages Eligible for Study:   60 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All Patients:

  • Adult patients, 60 to 80 years of age, inclusive
  • At least one bi-dimensionally measurable lesion, defined as > 1.5 cm in its longest dimension
  • Life expectancy of at least 24 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Adequate hematologic function (unless inadequate function is due to underlying disease, as established by extensive bone marrow involvement or is due to hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)

Dose-Escalation Portion of the Study:

  • Histologically confirmed B-cell NHL: Patients with newly diagnosed B-cell non-Hodgkin's lymphoma (NHL) or relapsed/refractory B-cell NHL are eligible
  • No more than one prior systemic treatment regimen for B-cell NHL (single agent anti-CD20 monoclonal antibody therapy will not be counted as a prior treatment regimen)
  • No prior treatment with anthracyclines

Expansion Portion of the Study:

  • Previously untreated patients with diffuse large B-cell lymphoma (DLBCL)
  • Age-adjusted IPI score of 2-3

Exclusion Criteria:

Dose-Escalation Portion of the Study:

  • Diagnosis of primary mediastinal DLBCL

Expansion Portion of the Study:

  • Patients with transformed lymphoma
  • Prior therapy for NHL

All Patients:

  • Prior stem cell transplant
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
  • Contraindication to receive any of the individual components of R-CHP
  • Current Grade > 1 peripheral neuropathy, with the exception of pre-phase treatment with prednisone/prednisolone
  • Ongoing corticosteroid use of > 30 mg/day of prednisone/prednisolone or equivalent. Patients receiving corticosteroid treatment with </= 30 mg/day of prednisone//prednisolone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration before Cycle 1 Day 1
  • Primary CNS lymphoma
  • History of other malignancy that could affect compliance with the protocol or interpretation of results Patients with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible.

Patients with a malignancy that has been treated with surgery alone with curative intent will also be excluded unless the malignancy has been in documented remission without treatment for >/= 5 years before enrollment.

  • Evidence of significant, uncontrolled concomitant diseases, including renal disease that would preclude chemotherapy administration, or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
  • Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina)
  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks before Cycle 1 Day 1
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Positive for hepatitis B or hepatitis C infection
  • Prior radiotherapy to the mediastinal/pericardial region
  • Pregnant or lactating women
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01992653

Contacts
Contact: Reference Study ID Number: GO29044 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
United States, Alabama
Not yet recruiting
Birmingham, Alabama, United States, 35233
United States, Missouri
Recruiting
St. Louis, Missouri, United States, 63110
United States, Oregon
Recruiting
Portland, Oregon, United States, 97210
Recruiting
Portland, Oregon, United States, 97239
Recruiting
Springfield, Oregon, United States, 97477
France
Recruiting
Creteil, France, 94010
Not yet recruiting
Lille, France, 59037
Recruiting
Pessac, France, 33604
Recruiting
Pierre Benite, France, 69495
Recruiting
Rennes, France, 35033
Not yet recruiting
Rouen, France, 76038
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

No publications provided

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01992653     History of Changes
Other Study ID Numbers: GO29044
Study First Received: October 28, 2013
Last Updated: October 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Prednisone
Rituximab
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 21, 2014