Combination Chemotherapy Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or High-Risk Primary Refractory Hodgkin Lymphoma

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Treatments

Procedure: allogeneic hematopoietic stem cell transplantation

Radiation: total-body irradiation

Procedure: peripheral blood stem cell transplantation

Drug: gemcitabine hydrochloride

Drug: cyclosporine

Procedure: allogeneic bone marrow transplantation

Drug: procarbazine hydrochloride

Drug: mycophenolate mofetil

Drug: vincristine sulfate

Drug: melphalan

Drug: vinorelbine tartrate

Drug: mechlorethamine hydrochloride

Drug: methotrexate

Drug: cyclophosphamide

Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation

Procedure: umbilical cord blood transplantation

Drug: ifosfamide

Drug: prednisone

Drug: fludarabine phosphate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00574496

MSKCC-07147

07-147

Details and patient eligibility

About

RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine, mycophenolate mofetil, and methotrexate before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well combination chemotherapy followed by donor stem cell transplant works in treating patients with relapsed or high-risk primary refractory Hodgkin lymphoma.

Full description

OUTLINE: Patients are stratified according to response to prior therapy and risk factors (those with presence of all 3 risk factors and failed primary therapy or primary progressive disease vs. patients who relapse more than 100 days after an autologous stem cell transplant).

Salvage chemotherapy (IGV or MOPP): Patients who have previously received mechlorethamine hydrochloride receive IGV; patients who have previously received a gemcitabine-based regimen receive MOPP.
- IGV (ifosfamide, gemcitabine hydrochloride, and vinorelbine ditartrate): Patients receive IGV combination chemotherapy comprising ifosfamide IV on days 1-4, gemcitabine hydrochloride IV on days 1 and 4, and vinorelbine ditartrate IV on day 1. Treatment repeats every 2-3 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity.
- MOPP (mechlorethamine hydrochloride, vincristine, procarbazine hydrochloride, and prednisone): Patients receive MOPP combination chemotherapy comprising mechlorethamine hydrochloride IV on days 1 and 8, vincristine IV on days 1 and 8, oral procarbazine hydrochloride on days 1-14, and oral prednisone on days 1-14. Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Patients with no progression of disease after salvage chemotherapy (at allograft work-up) proceed to allogeneic hematopoietic stem cell transplantation [AHSCT]* within 60 days after completion of salvage chemotherapy.

NOTE: *Patients with a nodal mass > 5 cm that has not ben previously irradiated and in the absence of extranodal disease may undergo involved-field radiotherapy twice daily for 2 weeks, prior to AHSCT.

AHSCT with reduced-intensity or non-myeloablative conditioning: Patients achieving partial response or stable disease after salvage therapy receive fludarabine phosphate IV over 30 minutes on days -6 to -2; melphalan IV over 15 minutes on days -6 and -5; and undergo AHSCT on day 0 (reduced-intensity conditioning). Patients achieving complete response after salvage therapy receive fludarabine phosphate IV over 30 minutes on days -6 to -2; cyclophosphamide IV over 15 minutes on day -6; total-body irradiation over 20-30 minutes on day -1; and undergo AHSCT on day 0 (non-myeloablative conditioning).
Graft-vs-host disease prophylaxis: Patients with related or unrelated donors receive cyclosporine IV over 2-4 hours or orally on days -3 to 100 followed by a taper, mycophenolate mofetil IV or orally on days -3 to 46 followed by a taper, and methotrexate IV on days 1, 3, 6, and 11.

Patients who received umbilical cord blood receive cyclosporine and mycophenolate mofetil as above (no methotrexate).

Follow-up period of 2 years post-transplant.

Enrollment

25 patients

Sex

All

Ages

13 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed classical Hodgkin lymphoma, including CD20+ disease
- No lymphocyte predominant histology
Primary refractory or relapsed disease with all 3 risk factors, failed platinum-based chemotherapy, or disease relapsed more than 100 days after autologous stem cell transplantation, proven by biopsy or fine-needle aspiration (cytology) of an involved site
- Risk factors are defined as B-symptoms, extranodal sites of disease, and disease remission lasting < 1 year after first-line therapy
Failed doxorubicin hydrochloride or mechlorethamine hydrochloride-containing front-line therapy
Fludeoxyglucose F 18-PET scan demonstrating PET-avid disease
No more than 2 prior salvage chemotherapy regimens (for patients proceed to allogeneic hematopoietic stem cell transplantation [AHSCT])
Donor available meeting 1 of the following criteria (for patients proceed to AHSCT):
- HLA-matched or one allele mismatched related donor
  - Genotypically or phenotypically matched at ≥ 9/10 of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution
  - Peripheral blood stem cells (PBSC) collected
- HLA-matched unrelated donor
  - Matched at ≥ 9/10 (allele mismatch only) of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution
  - PBSC or bone marrow collected
- Umbilical cord blood (2 units)
  - must be ≥ 4/6 HLA-A, B antigen, and DRB1 allele matched with recipient

PATIENT CHARACTERISTICS:

Platelet count > 50,000/mm^3
ANC > 1,000/mm^3
Cardiac ejection fraction > 50% (for patients ≥ 18 years of age)
Fractional shortening > 50% by echocardiogram* (for patients < 18 years of age)
Adjusted diffusing capacity > 50% on pulmonary function testing*
Serum creatinine < 1.5 mg/dL
Creatinine clearance ≥ 50 mL/min
Total bilirubin < 2.0 mg/dL in the absence of a history of Gilbert disease
HIV I and II negative
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Karnofsky performance status (PS) ≥ 70% or Lansky PS ≥ 70% (for patients proceed to AHSCT)
No active and uncontrolled infection at time of transplantation including active infection with Aspergillus or other mold (for patients proceed to AHSCT) NOTE: *measured since last chemotherapy

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior allogeneic transplantation
No more than 1 prior autologous transplantation
No inability to complete planned cytoreduction due to therapy complications

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

25 participants in 1 patient group

High-Risk or Relapsed Hodgkin Lymphoma

Experimental group

Description:

This is a phase 2 intention-to-treat study of salvage chemotherapy followed by allogeneic HSC transplant for the treatment of primary refractory or relapsed HL. Patients who 1) do not progress on salvage chemotherapy, and 2) have both suitable HSC donors and 3) a satisfactory pre-allograft work-up will proceed to allograft. Patients who fail any of these 3 criteria will be off-study and considered treatment failures for the purposes of the intention-to-treat study.

Treatment: