Bendamustine Bridge to Autologous or Allogeneic Transplant for Relapsed/Refractory Lymphoma

NCT02059239 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 1208012875
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is for men and women with whose lymphoma (non-Hodgkin or Hodgkin) did not respond to treatment or has returned after responding to previous therapy, and who are in need of a stem cell transplant. The purpose of this study is to test the safety and effectiveness of giving the drug Bendamustine, followed by high dose chemotherapy, within two weeks prior to a stem cell transplant for lymphoma that has not achieved a complete response to salvage (treatment used for relapsed disease) chemotherapy.

Conditions

Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma

Keywords

Non-Hodgkin's Lymphoma; Hodgkin's Lymphoma; Lymphoma; Transplant

Outcome Measures

Primary Outcomes (3)

• Number of Patients Able to Proceed to Transplant

  Number of patients in each arm able to proceed to stem cell transplantation within 14 days of receiving bendamustine treatment

  14 days after bendamustine treatment

• Number of Patients Achieving Neutrophil Engraftment

  Proportion of patients who successfully achieve neutrophil engraftment after stem cell transplant, defined as an absolute neutrophil count of 500/mm3 or for three consecutive days.

  35 Days Post-Transplant

• Number of Patients Achieving Platelet Engraftment

  Proportion of patients who successfully achieve platelet engraftment after stem cell transplant, defined as a platelet count of \>20k/microL for three consecutive days without transfusion support for seven consecutive days.

  74 Days Post-Transplant

Secondary Outcomes (7)

• Overall Survival at Day 100 Post-Transplant

  From Day 0 until time of death, assessed up to 100 days post-transplant

• Overall Survival at Day 365 Post-Transplant

  From Day 0 until time of death, assessed up to 365 days post-transplant

• Transplant-Related Mortality

  From Day 0 until time of death, up to 100 days post-transplant.

• Disease Response Following Salvage Chemotherapy

  Within 14 days of salvage chemotherapy treatment

• Disease Response 30 Days Post-Transplant

  30 days after stem cell transplant

Study Arms (2)

Chemo plus Autologous Transplantation

EXPERIMENTAL

Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by autologous transplant

Drug: Bendamustine; Drug: Carmustine; Drug: Etoposide; Drug: Melphalan; Drug: Cytarabine; Drug: Alemtuzumab; Biological: Autologous Stem Cell Transplantation; Drug: Rituximab

Chemo plus Allogeneic Transplantation

EXPERIMENTAL

Bendamustine 200 mg/ m2/ day on Days - 24 and Day - 23 followed by a short break of 10 - 14 days, followed by Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) and alemtuzumab, plus rituximab for all b-cell malignancies, followed by allogeneic transplant

Drug: Bendamustine; Drug: Carmustine; Drug: Etoposide; Drug: Melphalan; Drug: Cytarabine; Drug: Alemtuzumab; Biological: Allogeneic Stem Cell Transplantation; Drug: Rituximab

Interventions

Bendamustine DRUG

Days - 24 and Day - 23 followed by a short break of 10 - 14 days.

Also known as: Treanda

Chemo plus Allogeneic Transplantation; Chemo plus Autologous Transplantation

Carmustine DRUG

300 mg/m2 on Day -6

Also known as: Bicnu

Chemo plus Allogeneic Transplantation; Chemo plus Autologous Transplantation

Etoposide DRUG

100 mg/m2 on days -5 to -2

Also known as: Etopophos, Toposar

Chemo plus Allogeneic Transplantation; Chemo plus Autologous Transplantation

Melphalan DRUG

140mg/m2 on Day -1

Also known as: Alkeran

Chemo plus Allogeneic Transplantation; Chemo plus Autologous Transplantation

Cytarabine DRUG

200 mg/m2 on days -5 to -2

Also known as: Ara-C

Chemo plus Allogeneic Transplantation; Chemo plus Autologous Transplantation

Alemtuzumab DRUG

20 mg/m2 days -6 to -2 for UNRELATED donors, and 20 mg/m2 days -4 to -2 for RELATED donors

Also known as: Campath

Chemo plus Allogeneic Transplantation; Chemo plus Autologous Transplantation

Autologous Stem Cell Transplantation BIOLOGICAL

Chemo plus Autologous Transplantation

Allogeneic Stem Cell Transplantation BIOLOGICAL

Chemo plus Allogeneic Transplantation

Rituximab DRUG

Only to be administered in subjects with B-cell malignancies. Dose is 375 mg/m2 on Days 1 and 8 post-transplant

Also known as: Rituxan

Chemo plus Allogeneic Transplantation; Chemo plus Autologous Transplantation

Eligibility Criteria

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

You may qualify if:

• must have histologically or cytologically confirmed relapsed or primary refractory lymphoma (including Hodgkin's Lymphoma) staged with Positron Emission Tomography (PET) scan to have
• Allogeneic arm:
• Progressive disease or
• No response to salvage therapy or
• Partial response to salvage therapy defined as \> 50% reduction in bidirectional area of masses but standardized uptake value (SUV) remains ≥8 in at least some PET avid areas
• Prior autologous transplant
• Autologous arm:
• Partial response of \>50% reduction in bidirectional area of masses and SUV reduction to \<8 in PET avid areas Subjects must have evaluable disease.
• Subjects must have received at least one induction therapy and one line of salvage therapy that each incorporate at least two drugs that are standard of care for lymphoma
• Age \>18 years.
• Karnofsky Performance Score (KPS) ≥ 50%
• For autologous transplants: Subjects must have an adequate number of CD34+ stem cells collected to allow for transplantation. This number is defined as ≥ 2x106 CD34+ cells / kg body weight. If not previously collected and stored, the subject must be willing to undergo stem cell mobilization and collection as per standard practice. If sufficient cells cannot be collected, subjects will be offered the option to proceed with the allogeneic arm of the study.
• Male and female subjects must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. Female subjects of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Known to be positive for HIV
• Subjects may not be receiving any other investigational agents (defined as non FDA-approved agents) at the time of initiating bendamustine regimen. However, the salvage therapy for lymphoma can be part of an ongoing clinical trial with an investigational agent.
• Women who are pregnant or breast feeding. Women of childbearing age must use adequate contraception and have a negative pregnancy test.
• The risks to an unborn fetus or potential risks in nursing infants are unknown.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to any medications listed in the protocol.
• Subject with severely decreased Left Ventricular Ejection Fraction (LVEF) or severely impaired pulmonary function tests (PFT's)
• Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Related Publications (1)

• Orfali N, Jhanwar Y, Koo C, Pasciolla M, Baldo M, Cuvilly E, Furman R, Gergis U, Greenberg J, Guarneri D, Hsu JM, Leonard JP, Mark T, Mayer S, Maignan K, Martin P, Opong A, Pearse R, Phillips A, Rossi A, Ruan J, Rutherford SC, Ryan J, Suhu G, Van Besien K, Shore T. Sequential intensive chemotherapy followed by autologous or allogeneic transplantation for refractory lymphoma. Leuk Lymphoma. 2021 Jul;62(7):1629-1638. doi: 10.1080/10428194.2021.1881516. Epub 2021 Feb 13.

  PMID: 33586581 DERIVED

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin; Lymphoma

Interventions

Bendamustine Hydrochloride; Carmustine; Etoposide; etoposide phosphate; Melphalan; Cytarabine; Alemtuzumab; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived

Results Point of Contact

• Title: Dr. Tsiporah Shore
• Organization: Weill Cornell Medicine

tbs2001@med.cornell.edu

646-962-7950

Study Officials

• Tsiporah Shore, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2014
• First Posted: February 11, 2014
• Study Start: June 4, 2014
• Primary Completion: December 16, 2019
• Study Completion: June 15, 2020
• Last Updated: February 21, 2021
• Results First Posted: February 21, 2021

Record last verified: 2021-02

Locations

US (1)