Clinical trial NCT02059239: Bendamustine Bridge to Autologous or Allogeneic Transplant for Relapsed/Refractory Lymphoma
Official title: A Pilot Study of a Sequential Regimen of Intensive Chemotherapy Followed by Autologous or Allogeneic Transplantation for Refractory Lymphoma (Non-Hodgkin's and Hodgkin's) and Phase 2 Expansion Cohort
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hodgkin's Lymphoma
Non-Hodgkin's Lymphoma
Keywords: Non-Hodgkin's Lymphoma
Hodgkin's Lymphoma
Lymphoma
Transplant
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
First posted: 2014-02-11
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Patients Able to Proceed to Transplant
timeFrame: 14 days after bendamustine treatment
measure: Number of Patients Achieving Neutrophil Engraftment
timeFrame: 35 Days Post-Transplant
measure: Number of Patients Achieving Platelet Engraftment
timeFrame: 74 Days Post-Transplant
Secondary outcomes:
measure: Overall Survival at Day 100 Post-Transplant
timeFrame: From Day 0 until time of death, assessed up to 100 days post-transplant
measure: Overall Survival at Day 365 Post-Transplant
timeFrame: From Day 0 until time of death, assessed up to 365 days post-transplant
measure: Transplant-Related Mortality
timeFrame: From Day 0 until time of death, up to 100 days post-transplant.
measure: Disease Response Following Salvage Chemotherapy
timeFrame: Within 14 days of salvage chemotherapy treatment
measure: Disease Response 30 Days Post-Transplant
timeFrame: 30 days after stem cell transplant
measure: Disease Response at 1 Year Post-Transplant
timeFrame: 1 year after stem cell transplant
measure: Progression-Free Survival After Stem Cell Transplant
timeFrame: Stem cell transplant (Day 0) up to 2 years post-transplant
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Tsiporah Shore, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.