Tandem Auto-Allo Transplant for Lymphoma

NCT01181271 | Completed Phase 2 Results DMC

• 1 other identifier: 10-057
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

Relapse remains a principle cause of treatment failure for patients with aggressive lymphoma after autologous transplantation. Non-myeloablative allogeneic transplantation allows patients to receive an infusion of donor cells in an attempt to induce a graft versus lymphoma effect. This study will assess the feasibility, safety and efficacy of the combination of autologous stem cell transplantation followed by non-myeloablative transplantation for patients with poor-risk aggressive lymphoma.

Conditions

Diffuse, Large B-Cell, Lymphoma; Lymphoma, Low-Grade; T-Cell Lymphoma; Mantle-Cell Lymphoma; Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; Lymphoma, Small Lymphocytic

Keywords

Lymphoma; non-hodgkins lymphoma; Hodgkin's lymphoma; Hodgkin's disease; stem cell transplant; High-risk diffuse large B cell; Transformed low grade lymphoma; T-cell non-Hodgkin's lymphoma; Mantle cell lymphoma at any time in therapy; "Double-hit" lymphoma

Outcome Measures

Primary Outcomes (1)

• Peripheral Blood All-cell Donor Chimerism

  Successful donor stem cell engraftment is defined as when ≥ 80% of hematopoietic elements are donor-derived as determined by chimerism assays from peripheral blood at day 100 after non-myeloablative allogeneic stem cell transplantation.

  100 days post allogeneic transplant

Secondary Outcomes (11)

• Number of Days After Allogeneic Transplant Until Absolute Neutrophil Count Was Equal to or Greater Than 500/uL

  within 28 days after allogeneic transplant

• Cumulative Incidence of Grades II to IV Acute Graft Versus Host Disease (GVHD)

  within 200 days after allogeneic transplant

• Cumulative Incidence of Extensive Chronic Graft-versus-host-disease

  1-year after allogeneic transplant

• Cumulative Incidence of Non-relapse Mortality

  2-years after allogeneic transplant

• Cumulative Incidence of Disease Relapse

  2-years after allogeneic transplant

Study Arms (1)

Autologous then Allogeneic transplant

EXPERIMENTAL

All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).

Drug: Busulfan (conditioning for AUTO transplant); Drug: Etoposide (conditioning for AUTO transplant); Drug: Cyclophosphamide (conditioning for AUTO transplant); Drug: Mesna (prior to AUTO transplant); Other: autologous (auto) peripheral blood stem cell transplantation; Drug: Neupogen; Drug: Fludarabine (conditioning for ALLO Transplant); Drug: Busulfan (conditioning for ALLO Transplant); Other: non-myeloablative allogeneic (allo) transplant; Drug: Tacrolimus; Drug: Sirolimus; Drug: Methotrexate

Interventions

Busulfan (conditioning for AUTO transplant) DRUG

0.8 mg/kg intravenous (IV) bolus every six hours (Q6H) on days -8,-7,-6,-5 (total of 14 doses). The total daily dose of busulfan will be 3.2 mg/kg on days -8,-7, and -6 and 1.6 mg/kg on day -5

Also known as: Busulfex

Autologous then Allogeneic transplant

Etoposide (conditioning for AUTO transplant) DRUG

Etoposide 30 mg/kg IV bolus every day (QD) on day -4. The total daily dose of etoposide will be 30 mg/kg.

Also known as: VP-16

Autologous then Allogeneic transplant

Cyclophosphamide (conditioning for AUTO transplant) DRUG

Cyclophosphamide 60 mg/kg IV bolus QD on days -3 and -2. The total daily dose of cyclophosphamide will be 60 mg/kg.

Also known as: Cytoxan

Autologous then Allogeneic transplant

Mesna (prior to AUTO transplant) DRUG

Mesna 15 mg/kg IV bolus on days -3 and -2 infused over 15 minutes and given 15 minutes prior to cyclophosphamide administration. This is followed by Mesna given 15 mg/kg IV bolus three times daily (TID) on days -3 and -2 infused over 15 minutes at 3, 6, and 9 hours after completion of cyclophosphamide infusion. Total daily dose of Mesna should be equivalent to daily dose of cyclophosphamide. Lastly, Mesna will be given at 15 mg/kg IV bolus QD on day -1. This makes a total of 9 doses of Mesna

Autologous then Allogeneic transplant

autologous (auto) peripheral blood stem cell transplantation OTHER

Infusion of autologous peripheral blood stem cells on Day 0.

Autologous then Allogeneic transplant

Neupogen DRUG

Neupogen 5 mcg/kg subcutaneous (SQ) daily starting on day +1 until absolute neutrophil count (ANC) is greater than or equal to 1000 per micro liter on two separate occasions or greater than 5000 per micro liter once

Also known as: G-CSF

Autologous then Allogeneic transplant

Fludarabine (conditioning for ALLO Transplant) DRUG

Fludarabine 30 mg/m2/day will be administered as a bolus infusion over approximately 30 minutes for 4 days on days -5, -4, -3, -2.

Also known as: Fludara

Autologous then Allogeneic transplant

Busulfan (conditioning for ALLO Transplant) DRUG

Busulfan will be administered by IV infusion over approximately 3 hours on days -5, -4, -3, -2. The dose of busulfan will be 0.8 mg/kg/day

Also known as: Busulfex

Autologous then Allogeneic transplant

non-myeloablative allogeneic (allo) transplant OTHER

Donor peripheral blood stem cells (PBSC) will be infused intravenously beginning on Day 0. The minimum total CD34+ cell dose will be 2 x 10\^6 CD34+cells/kg of recipient's actual body weight with a maximum dose of 8 x 10\^6/kg of recipient's actual body weight

Autologous then Allogeneic transplant

Tacrolimus DRUG

Tacrolimus (FK506) will be given orally at a dose of 0.05 mg/kg orally (PO) twice a day (BID) starting day -3.

Also known as: FK506

Autologous then Allogeneic transplant

Sirolimus DRUG

Sirolimus (rapamycin) will be given orally at a dose of 12 mg times one on day -3 and then the dose shall be 4 mg by mouth daily starting on day -2. The dose may then be adjusted according to serum levels at the discretion of the treating physician

Also known as: Rapamycin

Autologous then Allogeneic transplant

Methotrexate DRUG

Methotrexate will be administered once daily on days 1, 3, and 6 as an IV bolus over 15 minutes at a dose of 5 mg/m2

Autologous then Allogeneic transplant

Eligibility Criteria

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

You may qualify if:

• Patients with high-risk diffuse large B cell or transformed low grade lymphoma defined as:
• Residual disease after at least 6 cycles of anthracycline-based chemotherapy (with residual disease defined as persistent bone marrow involvement and/or persistent measurable lymph node or solid organ masses that are PET or gallium avid)
• Progressive disease after at least 2 cycles of anthracycline-based chemotherapy
• Patients with an initial complete response but subsequent relapse within 6 months after completion of anthracycline-based chemotherapy
• Patients with any T-cell non-Hodgkin's lymphoma as defined as:
• Peripheral T-cell lymphoma (ALK negative PTCL-U) including PTCL-NOS, HSGD (hepato-splenic gamma-delta TCL), AITL (angioimmunoblastic T-cell lymphoma), EATL (enteropathy associated T-cell lymphoma), ALK-negative anaplastic large cell lymphoma
• Any T-cell histology (except LGL) with residual disease after at least 4 cycles of anthracycline-based chemotherapy (with residual disease defined as persistent bone marrow involvement and/or persistent measurable lymph node or solid organ masses that are PET or gallium avid)
• Patients with mantle cell lymphoma at any time in therapy
• Patients with "double-hit" lymphoma as characterized by the presence of concurrent overexpression of Bcl-2 and c-myc
• Patients with Hodgkin's lymphoma that is
• Refractory to first-line therapy and at least one second line chemotherapy regimen
• Relapsed Hodgkin's lymphoma which is refractory to at least one salvage chemotherapy regimen.
• Patients with CLL/SLL with 17p- cytogenetic abnormality
• Age 18 years and greater
• ECOG performance status 0-2

You may not qualify if:

• Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative transplant
• Pregnancy
• Evidence of HIV infection
• Heart failure uncontrolled by medications or ejection fraction less than 45%
• Active involvement of the CNS by lymphoma
• Inability to provide informed consent
• Previous autologous or allogeneic stem cell transplant
• Creatinine greater than 2 gm/dL or 24 hour urine creatinine clearance \< 50 cc/minute (does not have to satisfy both)
• Total bilirubin greater than 2 times the upper limit of normal except when due to Gilbert's syndrome or hemolysis.
• Transaminases greater than 3 times the upper limit of normal
• FVC or DLCO of less than 50% of predicted (DLCO corrected for hemoglobin level)
• Already known to not possess suitably HLA-matched related or unrelated donor
• Eligibility to proceed to allogeneic transplant Cannot be admitted for allogeneic transplant earlier than 40 days and no later than 180 days after autologous stem cell transplant.
• HLA identical (A, B, C and DR) related or unrelated donor available. HLA typing of class I loci (HLA- A, B, C) will be based on complement dependent cytotoxicity assay or PCR of sequence specific oligonucleotide primers (SSOP). Typing of HLA class II (DRB1) will be based on PCR of sequence specific oligonucleotide primers (SSOP).
• No need for intravenous hydration in the previous 2 weeks

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Chen YB, Li S, Fisher DC, Driscoll J, Del Rio C, Abramson J, Armand P, Barnes J, Brown J, Cutler C, El-Jawahri A, Ho VT, Hochberg E, McAfee S, Takvorian R, Spitzer TR, Antin JH, Soiffer R, Jacobsen E. Phase II Trial of Tandem High-Dose Chemotherapy with Autologous Stem Cell Transplantation Followed by Reduced-Intensity Allogeneic Stem Cell Transplantation for Patients with High-Risk Lymphoma. Biol Blood Marrow Transplant. 2015 Sep;21(9):1583-8. doi: 10.1016/j.bbmt.2015.05.016. Epub 2015 May 22.

  PMID: 26009261 RESULT

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma, Mantle-Cell; Hodgkin Disease; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma

Interventions

Busulfan; Etoposide; Cyclophosphamide; Mesna; Peripheral Blood Stem Cell Transplantation; Filgrastim; Granulocyte Colony-Stimulating Factor; fludarabine; fludarabine phosphate; Transplantation; Tacrolimus; Sirolimus; Methotrexate

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Sulfhydryl Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Surgical Procedures, Operative; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Macrolides; Lactones; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Yi-Bin Chen, MD
• Organization: Mass General Hospital

ychen6@partners.org

617-726-5765

Study Officials

• Yi-Bin A Chen, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 12, 2010
• First Posted: August 13, 2010
• Study Start: August 1, 2010
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2016
• Last Updated: March 9, 2017
• Results First Posted: March 9, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)