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

NCT ID: NCT02059239

Last Updated: 2021-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-04
• Study Completion Date: 2020-06-15

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.

Detailed Description

Subjects with Hodgkin's or Non-Hodgkin's lymphoma that did not respond to treatment or have disease that has returned after responding to previous treatment, and are in need of a stem cell transplant will be eligible for this pilot study. Thirty subjects will be enrolled, with 15 subjects assigned to the autologous transplant cohort (according to disease status and eligibility) and 15 subjects to the allogeneic transplant cohort (according to diseases status and eligibility).

Subjects will undergo the following a number of screening procedures to determine eligibility. All eligible subjects will receive bendamustine at a dose of 200 mg/ m2/ day for two days on Days - 24 and Day - 23 followed by a short break of 10 - 14 days. Subjects will then receive the conditioning regimen, BEAM (carmustine, etoposide, cytarabine arabinoside, and Melphalan) and alemtuzumab for 6 days (Day -6 to Day -1) followed by an autologous or allogeneic transplant.

Subjects with pathological confirmed B-cell malignancies will also receive rituximab 375 mg/m2 on Days + 1 and +8 post-transplant. Subjects with T-cell lymphoma will be enrolled in the study but will not receive rituximab.

After the transplantation all subjects will receive medication to prevent graft vs host disease and supportive care to prevent infections. To speed up the recovery of stem cells, subjects will receive post-transplant filgrastim (G-CSF).

After discharge from the hospital, subjects will be seen regularly in the clinic for an exam and assessments. All these tests are considered standard of care.

Conditions

Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemo plus Autologous Transplantation

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

Group Type: EXPERIMENTAL

Bendamustine

Intervention Type: DRUG

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

Carmustine

Intervention Type: DRUG

300 mg/m2 on Day -6

Etoposide

Intervention Type: DRUG

100 mg/m2 on days -5 to -2

Melphalan

Intervention Type: DRUG

140mg/m2 on Day -1

Cytarabine

Intervention Type: DRUG

200 mg/m2 on days -5 to -2

Alemtuzumab

Intervention Type: DRUG

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

Autologous Stem Cell Transplantation

Intervention Type: BIOLOGICAL

Rituximab

Intervention Type: DRUG

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

Chemo plus Allogeneic Transplantation

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

Group Type: EXPERIMENTAL

Bendamustine

Intervention Type: DRUG

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

Carmustine

Intervention Type: DRUG

300 mg/m2 on Day -6

Etoposide

Intervention Type: DRUG

100 mg/m2 on days -5 to -2

Melphalan

Intervention Type: DRUG

140mg/m2 on Day -1

Cytarabine

Intervention Type: DRUG

200 mg/m2 on days -5 to -2

Alemtuzumab

Intervention Type: DRUG

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

Allogeneic Stem Cell Transplantation

Intervention Type: BIOLOGICAL

Rituximab

Intervention Type: DRUG

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

Interventions

Bendamustine

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

Intervention Type: DRUG

Carmustine

300 mg/m2 on Day -6

Intervention Type: DRUG

Etoposide

100 mg/m2 on days -5 to -2

Intervention Type: DRUG

Melphalan

140mg/m2 on Day -1

Intervention Type: DRUG

Cytarabine

200 mg/m2 on days -5 to -2

Intervention Type: DRUG

Alemtuzumab

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

Intervention Type: DRUG

Autologous Stem Cell Transplantation

Intervention Type: BIOLOGICAL

Allogeneic Stem Cell Transplantation

Intervention Type: BIOLOGICAL

Rituximab

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

Intervention Type: DRUG

Other Intervention Names

Treanda; Bicnu; Etopophos; Toposar; Alkeran; Ara-C; Campath; Rituxan

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tsiporah Shore, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medical College

New York, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33586581 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1208012875

Identifier Type: -

Identifier Source: org_study_id