Cyclophosphamide and Alemtuzumab In Lymphoma

NCT03132584 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 17-034
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a combination of chemotherapy drugs as a possible treatment for aggressive lymphoma that has not responded to standard treatment. The names of the study interventions involved in this study are:

• Cyclophosphamide
• Alemtuzumab

Conditions

Non Hodgkin Lymphoma; High-grade B-cell Lymphoma; Diffuse Large B Cell Lymphoma

Keywords

Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• MTD of Cyclophosphamide and Alemtuzumab

  maximum tolerated dose of the combination of cyclophosphamide and alemtuzumab

  28 days

Secondary Outcomes (5)

• Overall Response Rate

  12 Months

• Complete Response Rate

  12 Months

• Progression Free Survival

  up to 5 years

• Overall Survival

  up to 5 years

• Response Rate

  28 Days

Study Arms (1)

Cyclophosphamide and Alemtuzumab

EXPERIMENTAL

After the screening procedures confirm participation in the research study: The investigators are looking for the highest dose of the combination of study drugs that can be administered safely without severe or unmanageable side effects in participants that have CD52 positive aggressive lymphoma. Not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well the dose was tolerated. * Cyclophosphamide * Alemtuzumab

Drug: Cyclophosphamide; Drug: Alemtuzumab

Interventions

Cyclophosphamide DRUG

The chemotherapy drugs will be given in the hospital. During the first cycle of treatment, participants will stay in the hospital until their blood counts have recovered after treatment. During cycles 2 and 3, participants may go home after chemotherapy if they are doing well. The length of each cycle is 28 days \- Via IV Day 3

Also known as: Endoxan, Cytoxan, Lyophilized Cytoxan, Neosar, Revimmune, Procytox, Cycloblastin

Cyclophosphamide and Alemtuzumab

Alemtuzumab DRUG

* The chemotherapy drugs will be given in the hospital. During the first cycle of treatment, participants will stay in the hospital until their blood counts have recovered after treatment. During cycles 2 and 3, participants may go home after chemotherapy if they are doing well. The length of each cycle is 28 days * Alemtuzumab will be administered as follows: * IV Day 1 * IV Day 2 * Target dose IV on Day 3 and 4

Also known as: Campath

Cyclophosphamide and Alemtuzumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically confirmed non-Hodgkin lymphoma and be considered ineligible for standard curative therapeutic options, including high dose chemotherapy with autologous stem cell rescue.
• Participants with the following subtypes of CD52 positive non-Hodgkin lymphoma (defined as ≥ 50% positive staining by immunohistochemical staining or flow cytometry by local lab) will be considered eligible:
• High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements (DHL)
• DLBCL or high-grade B-cell lymphoma NOS or B-cell lymphoma unclassifiable with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma with MYC and BCL2 protein over-expression by immunohistochemical (IHC) staining as defined by MYC expression in ≥ 40% of cells and BCL2 positivity ≥ 50% (DOL)
• Transformed lymphoma with MYC rearrangement by FISH or over-expression by IHC, as above
• CD52 positive mature T-cell lymphoproliferative disorder
• There is no limit to the prior number of chemotherapy regimens. Patients with prior autologous or allogeneic stem cell transplantation, as well as prior therapy with cyclophosphamide or alemtuzumab, are eligible.
• Age ≥ 18 and ≤75
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Participants must have normal organ and marrow function as defined by peripheral blood values below:
• leukocytes ≥1,000/mcL
• absolute neutrophil count ≥500/mcL
• platelets ≥25,000/mcL
• total bilirubin ≤ 2 × institutional upper limit of normal (ULN) unless related to Gilbert's disease
• AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 1 weeks (4 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Participants who are receiving any other investigational agents for their lymphoma.
• Participants receiving corticosteroids within the past 1 week.
• Participants with known active CNS involvement by lymphoma should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to cyclophosphamide or alemtuzumab
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hematuria related to bladder injury or psychiatric illness/social situations that could limit compliance with study requirements.
• Pregnant women are excluded from this study because cyclophosphamide and alemtuzumab at these doses have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued. Negative serum pregnancy test will be required for women of childbearing potential.
• HIV-positive participants on combination antiretroviral therapy are ineligible because of the increased risk of lethal infections when treated with marrow-suppressive therapy.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Genzyme, a Sanofi Company: collaborator
• Sanofi: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse

Interventions

Cyclophosphamide; Alemtuzumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ann LaCasce, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Model Details: This is a phase I study in the standard 3+3 dose escalation design

Study Record Dates

• First Submitted: April 24, 2017
• First Posted: April 28, 2017
• Study Start: July 30, 2017
• Primary Completion: January 30, 2018
• Study Completion: January 30, 2018
• Last Updated: January 14, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)